CaRLO

Description: BackgroundPrevious epidemiological studies have demonstrated the prevalence and relationship of various factors associated with sarcopenia in older adults; however, few have examined the status of sarcopenia in middle-aged adults. In this study, we aimed to, 1) evaluate the validity of the finger-circle test, which is potentially a useful screening tool for sarcopenia, and 2) determine the prevalence and factors associated with sarcopenia in middle-aged and older adults.MethodsWe conducted face-to-face surveys of 525 adults, who were aged 40–91 years and resided in Settsu City, Osaka Prefecture, Japan to evaluate the validity of finger-circle test. The finger-circle test evaluated calf circumference by referring to an illustration printed on the survey form. The area under the receiver operating characteristic curves (AUROC) was plotted to evaluate the validity of the finger-circle test for screening sarcopenia and compared to that evaluated by skeletal muscle mass index (SMI) measured using bioimpedance. We also conducted multisite population-based cross-sectional anonymous mail surveys of 9337 adults, who were aged 40–97 years and resided in Settsu and Hannan Cities, Osaka Prefecture, Japan. Participants were selected through stratified random sampling by sex and age in the elementary school zones of their respective cities. We performed multiple logistic regression analysis to explore associations between characteristics and prevalence of sarcopenia.ResultsSarcopenia, defined by SMI, was moderately predicted by a finger-circle test response showing that the subject’s calf was smaller than their finger-circle (AUROC: 0.729,

Description: BackgroundArea-proportional Euler diagrams are frequently used to visualize data from Microarray experiments, but are also applied to a wide variety of other data from biosciences, social networks and other domains.ResultsThis paper details Edeap, a new simple, scalable method for drawing area-proportional Euler diagrams with ellipses. We use a search-based technique optimizing a multi-criteria objective function that includes measures for both area accuracy and usability, and which can be extended to further user-defined criteria. The Edeap software is available for use on the web, and the code is open source. In addition to describing our system, we present the first extensive evaluation of software for producing area-proportional Euler diagrams, comparing Edeap to the current state-of-the-art; circle-based method, venneuler, and an alternative ellipse-based method, eulerr.ConclusionsOur evaluation—using data from the Gene Ontology database via GoMiner, Twitter data from the SNAP database, and randomly generated data sets—shows an ordering for accuracy (from best to worst) of eulerr, followed by Edeap and then venneuler. In terms of runtime, the results are reversed with venneuler being the fastest, followed by Edeap and finally eulerr. Regarding scalability, eulerr cannot draw non-trivial diagrams beyond 11 sets, whereas no such limitation is present in Edeap or venneuler, both of which draw diagrams up to the tested limit of 20 sets.

Description: BackgroundDefining the origin of genetic novelty is central to our understanding of the evolution of novel traits. Diversification among fatty acid desaturase (FAD) genes has played a fundamental role in the introduction of structural variation in fatty acyl derivatives. Because of its central role in generating diversity in insect semiochemicals, the FAD gene family has become a model to study how gene family expansions can contribute to the evolution of lineage-specific innovations. Here we used the codling moth (Cydia pomonella) as a study system to decipher the proximate mechanism underlying the production of the ∆8∆10 signature structure of olethreutine moths. Biosynthesis of the codling moth sex pheromone, (E8,E10)-dodecadienol (codlemone), involves two consecutive desaturation steps, the first of which is unusual in that it generates anE9 unsaturation. The second step is also atypical: it generates a conjugated diene system from theE9 monoene C12intermediate via 1,4-desaturation.ResultsHere we describe the characterization of the FAD gene acting in codlemone biosynthesis. We identify 27 FAD genes corresponding to the various functional classes identified in insects and Lepidoptera. These genes are distributed across theC. pomonellagenome in tandem arrays or isolated genes, indicating that the FAD repertoire consists of both ancient and recent duplications and expansions. Using transcriptomics, we show large divergence in expression domains: some genes appear ubiquitously expressed across tissue and developmental stages; others appear more restricted in their expression pattern. Functional assays using heterologous expression systems reveal that one gene, Cpo_CPRQ, which is prominently and exclusively expressed in the female pheromone gland, encodes an FAD that possesses bothE9 and ∆8∆10 desaturation activities. Phylogenetically, Cpo_CPRQ clusters within the Lepidoptera-specific ∆10/∆11 clade of FADs, a classic reservoir of unusual desaturase activities in moths.ConclusionsOur integrative approach shows that the evolution of the signature pheromone structure of olethreutine moths relied on a gene belonging to an ancient gene expansion. Members of other expanded FAD subfamilies do not appear to play a role in chemical communication. This advises for caution when postulating the consequences of lineage-specific expansions based on genomics alone.

Description: BackgroundThe binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed.ResultsHerein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes.ConclusionsOur results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.

Description: Background Pubic defects resulting from type III hemipelvectomy are commonly not reconstructed due to the need to preserve the weight-bearing axis. However, the opening of the anterior pelvic ring will inevitably lead to increased pelvic instability. To improve long-term pelvic stability, three-dimensional (3D)-printed customized prostheses were designed to reconstruct pubic defects. This study presents and evaluates the short-term clinical outcomes and complications from the use of this construct. Methods Five patients who underwent type III hemipelvectomy and 3D-printed customized prosthesis reconstruction at our institution between 2017 and 2019 were retrospectively analysed. Operation time and blood loss during the operation were recorded. Local and functional recovery was assessed. Prosthetic position and osseointegration were evaluated. Oncology results and complications were recorded. Results The prostheses consisted of three with stems and two without. The mean follow-up time was 23.6 months. At the last follow-up, all five patients were alive with no evidence of disease. No deep infections or local recurrence had occurred. The mean blood loss and mean intraoperative time were 1680 ml and 294 min, respectively. The mean functional MSTS score at the final follow-up was 29.8. Fretting wear around the prosthetic stem was found in 3 patients, while bone wear on the normal-side pubis was found in 2 patients. Osseointegration was observed in all patients. Conclusions 3D-printed customized prostheses for reconstructing pubic bone defects after type III hemipelvectomy showed acceptable early outcomes. The good outcomes were inseparable from the precision prosthesis design, strict surgical procedures, and sensible postoperative management.

Description: Background Patients living in more deprived localities have lower cancer survival in England, but the role of individual health status at diagnosis and the utilisation of primary health care in explaining these differentials has not been widely considered. We set out to evaluate whether pre-existing individual health status at diagnosis and primary care consultation history (peri-diagnostic factors) could explain socio-economic differentials in survival amongst women diagnosed with breast cancer. Methods We conducted a retrospective cohort study of women aged 15–99 years diagnosed in England using linked routine data. Ecologically-derived measures of income deprivation were combined with individually-linked data from the English National Cancer Registry, Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) databases. Smoking status, alcohol consumption, BMI, comorbidity, and consultation histories were derived for all patients. Time to breast surgery was derived for women diagnosed after 2005. We estimated net survival and modelled the excess hazard ratio of breast cancer death using flexible parametric models. We accounted for missing data using multiple imputation. Results Net survival was lower amongst more deprived women, with a single unit increase in deprivation quintile inferring a 4.4% (95% CI 1.4–8.8) increase in excess mortality. Peri-diagnostic co-variables varied by deprivation but did not explain the differentials in multivariable analyses. Conclusions These data show that socio-economic inequalities in survival cannot be explained by consultation history or by pre-existing individual health status, as measured in primary care. Differentials in the effectiveness of treatment, beyond those measuring the inclusion of breast surgery and the timing of surgery, should be considered as part of the wider effort to reduce inequalities in premature mortality.

Description: BubR1 is an essential component of the spindle assembly checkpoint (SAC) during mitosis where it functions to prevent anaphase onset to ensure proper chromosome alignment and kinetochore-microtubule attachment. Loss or mutation of BubR1 results in aneuploidy that precedes various potential pathologies, including cancer and mosaic variegated aneuploidy (MVA). BubR1 is also progressively downregulated with age and has been shown to be directly involved in the aging process through suppression of cellular senescence. Post-translational modifications, including but not limited to phosphorylation, acetylation, and ubiquitination, play a critical role in the temporal and spatial regulation of BubR1 function. In this review, we discuss the currently characterized post-translational modifications to BubR1, the enzymes involved, and the biological consequences to BubR1 functionality and implications in diseases associated with BubR1. Understanding the molecular mechanisms promoting these modifications and their roles in regulating BubR1 is important for our current understanding and future studies of BubR1 in maintaining genomic integrity as well as in aging and cancer.

Description: Background Socioeconomic differences in receipt of adjuvant treatment contribute to persistent disparities in breast cancer (BCA) outcomes, including survival. Adjuvant endocrine therapy (AET) substantially reduces recurrence risk and is recommended by clinical guidelines for nearly all women with hormone receptor-positive non-metastatic BCA. However, AET use among uninsured or underinsured populations has been understudied. The health reform implemented by the US state of Massachusetts in 2006 expanded health insurance coverage and increased the scope of benefits for many with coverage. This study examines changes in the initiation of AET among BCA patients in Massachusetts after the health reform. Methods We used Massachusetts Cancer Registry data from 2004 to 2013 for a sample of estrogen receptor (ER)-positive BCA surgical patients aged 20–64 years. We estimated multivariable regression models to assess differential changes in the likelihood initiating AET after Massachusetts health reform by area-level income, comparing women from lower- and higher-income ZIP codes in Massachusetts. Results There was a 5-percentage point (p-value

Description: Background ATP-binding cassette (ABC) transporters have been found to play important roles in metabolic transport in plant cells, influencing subcellular compartmentalisation and tissue distribution of these metabolic compounds. Salvia miltiorrhiza Bunge, known as Danshen in traditional Chinese medicine, is a highly valued medicinal plant used to treat cardiovascular and cerebrovascular diseases. The dry roots and rhizomes of S. miltiorrhiza contain biologically active secondary metabolites of tanshinone and salvianolic acid. Given an assembled and annotated genome and a set of transcriptome data of S. miltiorrhiza, we analysed and identified the candidate genes that likely involved in the bioactive metabolite transportation of this medicinal plant, starting with the members of the ABC transporter family. Results A total of 114 genes encoding ABC transporters were identified in the genome of S. miltiorrhiza. All of these ABC genes were divided into eight subfamilies: 3ABCA, 31ABCB, 14ABCC, 2ABCD, 1ABCE, 7ABCF, 46ABCG, and 10 ABCI. Gene expression analysis revealed tissue-specific expression profiles of these ABC transporters. In particular, we found 18 highly expressed transporters in the roots of S. miltiorrhiza, which might be involved in transporting the bioactive compounds of this medicinal plant. We further investigated the co-expression profiling of these 18 genes with key enzyme genes involved in tanshinone and salvianolic acid biosynthetic pathways using quantitative reverse transcription polymerase chain reaction (RT-qPCR). From this RT-qPCR validation, we found that three ABC genes (SmABCG46, SmABCG40, and SmABCG4) and another gene (SmABCC1) co-expressed with the key biosynthetic enzymes of these two compounds, respectively, and thus might be involved in tanshinone and salvianolic acid transport in root cells. In addition, we predicted the biological functions of S. miltiorrhiza ABC transporters using phylogenetic relationships and analysis of the transcriptome to find biological functions. Conclusions Here, we present the first systematic analysis of ABC transporters in S. miltiorrhiza and predict candidate transporters involved in bioactive compound transportation in this important medicinal plant. Using genome-wide identification, transcriptome profile analysis, and phylogenetic relationships, this research provides a new perspective on the critical functions of ABC transporters in S. miltiorrhiza.

Description: Background Forearm autotransplantation after parathyroidectomy has turned into the standard method for secondary hyperparathyroidism (SHPT) treatment in chronic kidney disease patients. Our study aimed to explore the effects of three methods including muscle, subcutaneous and muscle + subcutaneous transplant methods on SHPT. Methods Seventy five SHPT patients were enrolled and assigned into the muscle + subcutaneous (M + S) (n = 26), muscle (M) (n = 35), and subcutaneous (S) (n = 14) groups. The operation efficacy evaluation included preoperative and postoperative biological characteristics such as parathyroid hormone (PTH), serum phosphorus, serum calcium and alkaline phosphatase (ALP). The data were recorded from pre-operation time point to 1, 2, 3, 6, 12, 18, 24 month (mo) postoperation periods. After operation, short-form health survey (SF-36) scores was made for life quality identification at 1, 2, 3, 6, 12, 24 time points. Symptoms about SHPT including bone pain, fracture, pruritus, and coronary artery calcification were followed-up based on the scale. Results Compared with the preoperative record, all the M + S, M, and S groups showed postoperative decreased levels of PTH, serum phosphorus, serum calcium, calcium-phosphorus. In M + S group, the PTH and serum calcium level kept more steady compared with the M and S groups during a 24 mo duration observation. After this, a SF-36 score scale which represents the life quality show M + S group got more scores at 3, 6, 12, 18 and 24 mo points. At last, the incidence of SHPT associated symptoms including Bone pain, Fracture, Pruritus, and Coronary artery calcification in M + S group were decreased compared with M and S groups at 1, 3, 6, 12 and 24 mo post-operation time points. Conclusion M + S seems to be an efficient method for medical treatment of SHPT patients in the control of PTH and serum calcium. This mixed transplant strategy improves the biochemical characterizes compared with M and S groups in SHPT patients. Furthermore, the M + S method make beneficial on clinical outcomes and life quality of patients.

Description: Background Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC. Methods The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level. Results The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.

Description: Background Endothelial progenitor cell (EPC) dysfunction contributes to vascular disease in diabetes mellitus. However, the molecular mechanism underlying EPC dysfunction and its contribution to delayed reendothelialization in diabetes mellitus remain unclear. Our study aimed to illustrate the potential molecular mechanism underlying diabetic EPC dysfunction in vivo and in vitro. Furthermore, we assessed the effect of EPC transplantation on endothelial regeneration in diabetic rats. Methods Late outgrowth EPCs were isolated from the bone marrow of rats for in vivo and in vitro studies. In vitro functional assays and Western blotting were conducted to reveal the association between C-X-C chemokine receptor type 7 (CXCR7) expression and diabetic EPC dysfunction. To confirm the association between cellular CXCR7 levels and EPC function, CXCR7 expression in EPCs was upregulated and downregulated via lentiviral transduction and RNA interference, respectively. Western blotting was used to reveal the potential molecular mechanism by which the Stromal-Derived Factor-1 (SDF-1)/CXCR7 axis regulates EPC function. To elucidate the role of the SDF-1/CXCR7 axis in EPC-mediated endothelial regeneration, a carotid artery injury model was established in diabetic rats. After the model was established, saline-treated, diabetic, normal, or CXCR7-primed EPCs were injected via the tail vein. Results Diabetic EPC dysfunction was associated with decreased CXCR7 expression. Furthermore, EPC dysfunction was mimicked by knockdown of CXCR7 in normal EPCs. However, upregulating CXCR7 expression reversed the dysfunction of diabetic EPCs. The SDF-1/CXCR7 axis positively regulated EPC function by activating the AKT-associated Kelch-like ECH-associated protein 1 (keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis, which was reversed by blockade of AKT and Nrf2. Transplantation of CXCR7-EPCs accelerated endothelial repair and attenuated neointimal hyperplasia in diabetes mellitus more significantly than transplantation of diabetic or normal EPCs. However, the therapeutic effect of CXCR7-EPC transplantation on endothelial regeneration was reversed by knockdown of Nrf2 expression. Conclusions Dysfunction of diabetic EPCs is associated with decreased CXCR7 expression. Furthermore, the SDF-1/CXCR7 axis positively regulates EPC function by activating the AKT/keap-1/Nrf2 axis. CXCR7-primed EPCs might be useful for endothelial regeneration in diabetes-associated vascular disease.

Description: Background DNA methylation is an important epigenetic control mechanism that in many fungi is restricted to genomic regions containing transposable elements (TEs). Two DNA methyltransferases, Dim2 and Dnmt5, are known to perform methylation at cytosines in fungi. While most ascomycete fungi encode both Dim2 and Dnmt5, only few functional studies have been performed in species containing both. Methods In this study, we report functional analysis of both Dim2 and Dnmt5 in the plant pathogenic fungus Verticillium dahliae. Results Our results show that Dim2, but not Dnmt5 or the putative sexual-cycle-related DNA methyltransferase Rid, is responsible for the majority of DNA methylation under the tested conditions. Single or double DNA methyltransferase mutants did not show altered development, virulence, or transcription of genes or TEs. In contrast, Hp1 and Dim5 mutants that are impacted in chromatin-associated processes upstream of DNA methylation are severely affected in development and virulence and display transcriptional reprogramming in specific hypervariable genomic regions (so-called adaptive genomic regions) that contain genes associated with host colonization. As these adaptive genomic regions are largely devoid of DNA methylation and of Hp1- and Dim5-associated heterochromatin, the differential transcription is likely caused by pleiotropic effects rather than by differential DNA methylation. Conclusion Overall, our study suggests that Dim2 is the main DNA methyltransferase in V. dahliae and, in conjunction with work on other fungi, is likely the main active DNMT in ascomycetes, irrespective of Dnmt5 presence. We speculate that Dnmt5 and Rid act under specific, presently enigmatic, conditions or, alternatively, act in DNA-associated processes other than DNA methylation.

Description: Background Spinach has high antioxidants and polyphenols and showed protective effects against liver diseases in experimental studies. We aimed to assess the association between dietary intake of spinach and odds of nonalcoholic fatty liver disease (NAFLD) in a case–control study among Iranian adults. Methods Totally 225 newly diagnosed NAFLD patients and 450 controls, aged 20–60 years, were recruited in this study. Participants’ dietary intakes were collected using a valid and reliable 168-item semi-quantitative food frequency questionnaire (FFQ). The logistic regression test was used for assessing the association between total, raw, and boiled dietary spinach with the odds of NAFLD. Results The mean (SD) age and BMI of participants (53% male) were 38.1 (8.8) years and 26.8 (4.3) kg/m2, respectively. In the final adjusted model for potential confounders, the odds (95% CI) of NAFLD in individuals in the highest tertile of daily total and raw spinach intake was [0.36 (0.19–0.71), P_trend = 0.001] and [0.47 (0.24–0.89), P_trend = 0.008], respectively compared with those in the lowest tertile. Furthermore, in the adjusted analyses, an inverse association was observed between the highest yearly intake versus no raw spinach consumption and odds of NAFLD [(OR 0.41; 95% CI 0.18–0.96), P for trend = 0.013]. However, there was no significant association between higher boiled spinach intake and odds of NAFLD. Conclusions The present study found an inverse association between total and raw spinach intake with the odds of NAFLD.

Description: Background Although there is growing recognition of the importance of person-centered maternity care, the needs and perspectives of pregnant adolescents are rarely considered. The purpose of this study was to compare the maternity care experiences of Mexican-origin adolescents in Guanajuato, Mexico and Fresno, California from both youth and healthcare provider perspectives. Methods Qualitative interviews and focus groups were conducted with a total of 89 respondents, including 74 pregnant and parenting adolescents as well as 15 providers between December 2016 and July 2017. Adolescents also completed a short demographic survey prior to participation. Transcripts in English and Spanish were coded and thematically analyzed using Dedoose software. Results were compared by location and between youth and providers. Results Four themes emerged regarding patient-provider interactions: the need for communication and clear explanations, respectful versus judgmental providers, engaging youth in decision-making, and a focus on the age of the youth and their partners. While youth had similar perspectives and priorities in both locations, youth in Mexico reported more negative healthcare experiences than youth in California. Perspectives varied between the youth and providers, with providers in both California and Mexico identifying several structural challenges in providing quality care to adolescents. In California, challenges to supporting immigrant Latina adolescents and their families included language and translation issues as well as barriers to care due to immigration status and documentation. In both locations, providers also mentioned high patient caseloads and their own concerns about the youth’s life choices. Conclusion Youth-centered care requires more effective and respectful patient-provider communication, where adolescents are engaged in their healthcare decision-making and delivery options. Changes in patient-provider interactions can help improve the maternity care experiences and outcomes of Latina adolescents. Healthcare systems and providers need to reconfigure their approaches to focus on the needs and priorities of adolescents.

Description: Background Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. Method All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007–2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days’ follow-up. Results The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21–64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days’ follow-up. Conclusion The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Description: Background Breast cancer is the most common cancer among women and the second leading cause of cancer death globally. Since early diagnosis is crucial to reducing mortality, high levels of knowledge regarding general information, risk factors, and symptoms are required among healthcare professionals to deliver breast cancer care. This study aimed to determine Syrian medical students’ knowledge about breast cancer in the fields of general knowledge, common clinical features, and risk factors. Methods This cross-sectional study was conducted at the Syrian Private University in October 2019 (Breast Cancer Awareness Month), Damascus, during the Syrian war crisis. Data were collected through self-administered surveys and analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS Inc., United States). The chi-square test was applied to assess the relationship between the level of knowledge and gender. One way analysis of variance was performed to assess the overall differences in mean knowledge score by study year, GPA, mother’s education, and source of information. Unpaired Student’s T-test was used to analyze the differences in mean knowledge scores (continuous variable) based on smoking status and alcohol consumption. Results Of 320 students, 301 completed the questionnaire (response rate = 94.0%), of which 179(59.5%) were males. The study revealed above-average knowledge scores (total mean = 68.4%) regarding breast cancer, general information (71.9%), common clinical features (71.6%), and risk factors (71.6%). Clinical students (4th, 5th, and 6th years) scored higher compared with pre-clinical students (1st, 2nd, and 3rd years). Conclusion This study showed above-average knowledge scores regarding breast cancer. More efforts to correct misinformation, through reassessing the university curriculum and promoting awareness about breast cancer are required.

Description: Background There is limited evidence of Aboriginal and Torres Strait Islander people attending cardiac rehabilitation (CR) programs despite high levels of heart disease. One key enabler for CR attendance is a culturally safe program. This study evaluates improving access for Aboriginal and Torres Strait Islander women to attend a CR program in a non-Indigenous health service, alongside improving health workforce cultural safety. Methods An 18-week mixed-methods feasibility study was conducted, with weekly flexible CR sessions delivered by a multidisciplinary team and an Aboriginal and/or Torres Strait Islander Health Worker (AHW) at a university health centre. Aboriginal and Torres Strait Islander women who were at risk of, or had experienced, a cardiac event were recruited. Data was collected from participants at baseline, and at every sixth-session attended, including measures of disease risk, quality-of-life, exercise capacity and anxiety and depression. Cultural awareness training was provided for health professionals before the program commenced. Assessment of health professionals’ cultural awareness pre- and post-program was evaluated using a questionnaire (n = 18). Qualitative data from participants (n = 3), the AHW, health professionals (n = 4) and referrers (n = 4) was collected at the end of the program using yarning methodology and analysed thematically using Charmaz’s constant comparative approach. Results Eight referrals were received for the CR program and four Aboriginal women attended the program, aged from 24 to 68 years. Adherence to the weekly sessions ranged from 65 to 100%. At the program’s conclusion, there was a significant change in health professionals’ perception of social policies implemented to ‘improve’ Aboriginal people, and self-reported changes in health professionals’ behaviours and skills. Themes were identified for recruitment, participants, health professionals and program delivery, with cultural safety enveloping all areas. Trust was a major theme for recruitment and adherence of participants. The AHW was a key enabler of cultural authenticity, and the flexibility of the program contributed greatly to participant perceptions of cultural safety. Barriers for attendance were not unique to this population. Conclusion The flexible CR program in a non-Indigenous service provided a culturally safe environment for Aboriginal women but referrals were low. Importantly, the combination of cultural awareness training and participation in the program delivery improved health professionals’ confidence in working with Aboriginal people. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) 12618000581268, http://www.ANZCTR.org.au/ACTRN12618000581268.aspx, registered 16 April 2018.

Description: Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

Description: Background Less experienced clinicians sometimes make misdiagnosis of hip fractures. We developed computer-aided diagnosis (CAD) system for hip fractures on plain X-rays using a deep learning model trained on a large dataset. In this study, we examined whether the accuracy of the diagnosis of hip fracture of the residents could be improved by using this system. Methods A deep convolutional neural network approach was used for machine learning. Pytorch 1.3 and Fast.ai 1.0 were applied as frameworks, and an EfficientNet-B4 model (a pre-trained ImageNet model) was used. We handled the 5295 X-rays from the patients with femoral neck fracture or femoral trochanteric fracture from 2009 to 2019. We excluded cases in which the bilateral hips were not included within an image range, and cases of femoral shaft fracture and periprosthetic fracture. Finally, we included 5242 AP pelvic X-rays from 4851 cases. We divided these 5242 images into two images per image, and prepared 5242 images including fracture site and 5242 images without fracture site. Thus, a total of 10,484 images were used for machine learning. The accuracy, sensitivity, specificity, F-value, and area under the curve (AUC) were assessed. Gradient-weighted class activation mapping (Grad-CAM) was used to conceptualize the basis for the diagnosis of the fracture by the deep learning algorithm. Secondly, we conducted a controlled experiment with clinicians. Thirty-one residents;young doctors within 2 years of graduation from medical school who rotate through various specialties, were tested using 300 hip fracture images that were randomly extracted from the dataset. We evaluated the diagnostic accuracy with and without the use of the CAD system for each of the 300 images. Results The accuracy, sensitivity, specificity, F-value, and AUC were 96.1, 95.2, 96.9%, 0.961, and 0.99, respectively, with the correct diagnostic basis generated by Grad-CAM. In the controlled experiment, the diagnostic accuracy of the residents significantly improved when they used the CAD system. Conclusions We developed a newly CAD system with a deep learning algorithm from a relatively large dataset from multiple institutions. Our system achieved high diagnostic performance. Our system improved the diagnostic accuracy of residents for hip fractures. Level of evidence Level III, Foundational evidence, before-after study. Clinical relevance: high

Description: Background Although the workers in many occupations are at the greatest risk of catching and spreading COVID-19 due to assembling and contacting people, the owners of these occupations do not follow COVID-19 health instructions. The purpose of this study is to explain the reasons for not maintaining health guidelines to prevent COVID-19 in high-risk jobs in Iran. Methods The present study was conducted with a qualitative approach among people with high-risk jobs in Tehran during March and April of 2020. Data were collected through semi-structured interviews with 31 people with high-risk occupations selected by purposeful sampling and snowballing. The data were analyzed using the conventional qualitative content analysis method and MAXQDA-18 software. Guba and Lincoln’s criteria were also used to evaluate the quality of the research results. Results 4 main categories and 13 sub-categories were obtained, including individual factors (personality traits, lack of self-efficacy, little knowledge of the disease and how to observe health norms related to it, misconceptions about health), structural factors (difficulty of access to health supplies, lack of supportive environment, weak laws and supervision, the poor performance of officials and national media), economic factors (economic costs of living, lack of government economic support), Socio-cultural factors (learning, cultural beliefs, social customs, and rituals). Conclusion COVID-19 prevention requires intervention at different levels. At the individual level: increasing people’s awareness and understanding about how to prevent COVID-19 and strengthening self-efficacy in observing health norms, at the social level: highlighting positive patterns of observing health issues and training people about the consequences of social interactions during the outbreak of the virus, and at the macro level: strengthening regulatory rules and increasing people’s access to hygienic products and support for the vulnerable must be taken into account.

Description: Background The aim of this study was to analyze the seasonal distribution of the nematode Hedruris dratini parasitizing the South American Snake-necked turtle Hydromedusa tectifera and the amphipod Hyalella spp. in an urban stream. We focused on understand which strategies parasite population displays to get through the host’s hibernation period. Results The highest prevalence and abundance of H. dratini were found in summer. The parasitic load was lower in winter, however there were no significant differences when it was compared with autumn and spring. Generalized linear model identified the temperature as a determining factor for the presence of parasites in turtles. Conclusions Our results indicate that, beside turtles enter in a diapause state, the life cycle of H. dratini never stop throughout the year, being a continuous transmission between both the intermediate and final host throughout the year. Turtles feed and become infected with parasite larvae even in winter although with a lower ingestion rate.

Description: Background There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited. Methods Two population-based UK primary care cohorts were delineated in the Aurum and GOLD datasets of the Clinical Practice Research Datalink (CPRD). We included data from 9,133,246 individuals aged 1–20 who contributed 117,682,651 person-years of observation time. Sex- and age-stratified annual incidence rates were estimated for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) (age groups: 1–5, 6–9, 10–12, 13–16, 17–19), depression, anxiety disorders (6–9, 10–12, 13–16, 17–19), eating disorders and self-harm (10–12, 13–16, 17–19) during 2003–2018. We fitted negative binomial regressions to estimate incidence rate ratios (IRRs) to examine change in incidence between the first (2003) and final year (2018) year of observation and to examine sex-specific incidence. Results The results indicated that the overall incidence has increased substantially in both boys and girls in between 2003 and 2018 for anxiety disorders (IRR 3.51 95% CI 3.18–3.89), depression (2.37; 2.03–2.77), ASD (2.36; 1.72–3.26), ADHD (2.3; 1.73–3.25), and self-harm (2.25; 1.82–2.79). The incidence for eating disorders also increased (IRR 1.3 95% CI 1.06–1.61), but less sharply. The incidence of anxiety disorders, depression, self-harm and eating disorders was in absolute terms higher in girls, whereas the opposite was true for the incidence of ADHD and ASD, which were higher among boys. The largest relative increases in incidence were observed for neurodevelopmental disorders, particularly among girls diagnosed with ADHD or ASD. However, in absolute terms, the incidence was much higher for depression and anxiety disorders. Conclusion The number of young people seeking help for psychological distress appears to have increased in recent years. Changes to diagnostic criteria, reduced stigma, and increased awareness may partly explain our results, but we cannot rule out true increases in incidence occurring in the population. Whatever the explanation, the marked rise in demand for healthcare services means that it may be more challenging for affected young people to promptly access the care and support that they need.

Description: Background The coronavirus disease 2019 (COVID-19) pandemic continues to expand. Herein, we report the epidemiological and clinical features of 478 patients with confirmed COVID-19 from a multicenter study conducted in four cities in China excluding Wuhan. Methods A total of 478 patients transferred by emergency medical services to designated hospitals in four major cities in China (Beijing, Chongqing, Jinan, and Nanning) were enrolled. We compared the characteristics of imported and indigenous cases and calculated the frequencies of fatal, severe, mild, and asymptomatic disease. The results were used to generate a pyramid of COVID-19 severity. Results The mean age of patients with COVID-19 was 46.9 years and 49.8% were male. The most common symptoms at onset were fever (69.7%), cough (47.5%), fatigue (24.5%), dyspnea (8.4%), and headache (7.9%). Most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. Imported cases dominated during the early stages of the pandemic, but decreased from 1 February 2020 as indigenous cases rose sharply. Compared with indigenous cases, imported cases differed significantly in terms of sex (P = 0.002), severity of disease (P = 0.006), occurrence of fever (P 

Description: Background Venous thromboembolism clinically presenting with a deep vein thrombosis or pulmonary embolism is among the most commonly seen cardiovascular syndromes. The aim of this case presentation is to emphasise the typical electrocardiographic findings that are detected with massive pulmonary embolism along with the electrocardiographic S1Q3 and S1Q3T3 accompanied by T negativity at the D3 derivation based on prevalent T negativity. Case presentation We present the case of an adult male who presented with a massive pulmonary embolism that was associated with tachycardia, haemoptysis and typical S1Q3T3 electrocardiographic findings. Tomographic findings showed filling defects in the two main pulmonary artery lumens, which were found to be compatible with a massive embolism. Intravenous heparin was injected (5000 IU), and low molecule weight heparin (LMWH) treatment was initiated. After two days of observation and treatment in the coronary intensive care unit, the patient was discharged for outpatient care. Discussion Massive pulmonary embolism is an urgent life-threatening clinical situation that is frequently confused with acute ST elevation myocardial infarction. The definitive diagnosis of massive pulmonary embolism was made with a computed tomography pulmonary angiogram. Electrocardiographic findings and hypoxic hypercarbia in the blood gas analysis are typical. Early diagnosis with laboratory and imaging investigations is vital in the treatment and prognosis of pulmonary embolism. Conclusions Ventricular overload signs accompanied by ST segment elevation in electrocardiography and S1Q3 and prevalent T negativity are crucial features in terms of distinguishing between pulmonary embolism and myocardial infarction and selecting effective treatments for patients admitted to the emergency department.

Description: Background No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS. Methods A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was 〉 10 IU/L, and/or a follicle with mean diameter 〉 12 mm was present, and/or serum E2 was 〉 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group. Result(s) No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol. Conclusion(s) Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration. Trial registration NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.

Description: Background Maternal age  34 years, short inter-pregnancy birth interval, and higher birth order are considered to be high-risk fertility behaviours (HRFB). Underfive mortality being disproportionately concentrated in Asia and Africa, this study analyses the association between HRFB and underfive mortality in selected Asian and African countries. Methods This study used Integrated Public Microdata Series-Demographic and Health Surveys (IPUMS-DHS) data from 32 countries in sub-Saharan Africa, Middle East, North Africa and South Asia from 1986 to 2017 (N = 1,467,728). Previous evidence hints at four markers of HRFB: women’s age at birth of index child  34 years, preceding birth interval  3. Using logistic regression, we analysed change in the odds of underfive mortality as a result of i) exposure to HRFB individually, ii) exposure to any single HRFB risk factor, iii) exposure to multiple HRFB risk factors, and iv) exposure to specific combinations of HRFB risk factors. Results Mother’s age at birth of index child

Description: Background The availability of large epidemiological or clinical data storing biological samples allow to study the prognostic value of novel biomarkers, but efficient designs are needed to select a subsample on which to measure them, for parsimony and economical reasons. Two-phase stratified sampling is a flexible approach to perform such sub-sampling, but literature on stratification variables to be used in the sampling and power evaluation is lacking especially for survival data. Methods We compared the performance of different sampling designs to assess the prognostic value of a new biomarker on a time-to-event endpoint, applying a Cox model weighted by the inverse of the empirical inclusion probability. Results Our simulation results suggest that case-control stratified (or post stratified) by a surrogate variable of the marker can yield higher performances than simple random, probability proportional to size, and case-control sampling. In the presence of high censoring rate, results showed an advantage of nested case-control and counter-matching designs in term of design effect, although the use of a fixed ratio between cases and controls might be disadvantageous. On real data on childhood acute lymphoblastic leukemia, we found that optimal sampling using pilot data is greatly efficient. Conclusions Our study suggests that, in our sample, case-control stratified by surrogate and nested case-control yield estimates and power comparable to estimates obtained in the full cohort while strongly decreasing the number of patients required. We recommend to plan the sample size and using sampling designs for exploration of novel biomarker in clinical cohort data.

Description: Background The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. Methods Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. Results The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD

Description: Background The support of student wellbeing features highly in all higher education institutional agendas. For medical students good physical and mental health can help prevent burnout, equip students for their future healthcare setting and indirectly improve patient care. At the University of Nottingham (UK), we were keen to explore undergraduate medical students perceived wellbeing before, during, and after an early years’ (years 1-3) curriculum change. A restructure of the curriculum enabled personal wellbeing sessions to be embedded and directly linked to the pastoral support system. Methods Students’ perceived wellbeing was assessed through a questionnaire distributed to three cohorts of first year students at the start and end of the autumn semester. Results The data showed a clear improvement of perceived physical health at the end of the first semester following the curriculum change, alongside increased mood and ability to relax. A surprising outcome of this study was that students reported increased stress levels at the end of the semester, which we believe may be attributed to the change in assessment within the new curriculum. Our medical students are now facing end of year summative examinations, but are acutely aware of their progress as they undertake frequent formative assessments during the year. We propose that comparison of performance with peers is having a direct impact on perceived stress in these cohorts. Conclusions The study has shown that embedding wellbeing in the curriculum can have positive effects even within a changing curriculum. The importance of evolving wellbeing provision and support based on the needs of the student population is essential and probably never more in need than at this moment in time.

Description: Background A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. Methods In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. Results Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23–0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16–10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29–5.65) as independent risk factors for OS. Conclusion Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

Description: Background Grant funding often drives innovative programming in efforts to enhance diversity in biomedical fields, yet strategies for sustainability of grant-funded biomedical intervention are not well understood. Additionally, as funding agencies shift toward supporting institutional change to biomedical training, less is known about the extent to which sustainability strategies can support long-term institutionalization of the original goals of the grant-funded initiative. The purpose of this study is twofold: to identify strategies used by grant-funded programs for promoting sustainability, and to examine the interrelations between the concepts of sustainability and institutionalization during early stages of grant-funded biomedical career training efforts. Methods We employed a multiple case study design and cross-case analysis using interviews of program administrators and participants from 10 undergraduate institutions that received Building Infrastructure Leading to Diversity (BUILD) awards funded by the National Institutes of Health (NIH). Results BUILD sites engaged in the following strategies to develop program sustainability: 1) scaling and adapting to expand programmatic impact, 2) identifying additional funding and cost-cutting measures, 3) developing and maintaining infrastructure and structural operations, 4) leveraging relationships and with intra-and inter-institutional partners, and 5) and addressing hiring, policies, and reward systems at the institution. Senior administrative support supported program sustainability and early institutionalization, although we also identified situations where participants felt that they were on track for sustainable changes without administrative support or institutional change. Of the strategies identified, those that involve organizational and infrastructural changes contribute to early stages of institutionalization. Conclusions This study contributes to literature on organizational change by providing evidence of distinctions and interrelations between program sustainability efforts and institutionalization of change efforts in that some sustainability strategies can overlap with strategies to move toward institutionalization. The findings indicate the importance of program administrators developing early sustainability plans that also lead to institutionalization, as well as an opportunity for funding agencies to develop technical assistance on sustainability, organizational change, and institutionalization as a resource to support program administrators’ efforts toward making lasting, structural change on their campuses.

Description: Background Population growth and general practitioner workforce constraints are creating increasing demand for health services in New Zealand (NZ) and internationally. Non-medical prescribing (NMP) is one strategy that has been introduced to help manage this. Little is known about the NMP practice trends in NZ. The aim of this study was to provide a current overview of the scale, scope, and trends of NMP practice in NZ. Methods All claims for community dispensed medicines prescribed by a non-medical prescriber were extracted from the NZ Pharmaceutical Collection for the period 2016–2020. Patient demographics were retrieved from the Primary Health Organisation enrolment collection. These national databases contain prescription information for all subsidised community pharmacy medicines dispensed and healthcare enrolment data for 96% of New Zealanders. Results The proportion of prescriptions written by all NMP providers and patients receiving NMP prescriptions increased each year from 1.8% (2016) to 3.6% (2019) and 8.4% (2016) to 14.4% (2019) respectively. From 2016 to 2019, the proportion of NMP patients who had at least one NMP prescription increased from 26% to 39% for nurse prescribers, from 1% to 9% for pharmacist prescribers, from 2% to 3% for dietitian prescribers, and decreased from 47% to 22% for dentists, and from 20% to 12% for midwives. The most commonly prescribed medicines were antibiotics (amoxicillin, amoxicillin with clavulanic acid, and metronidazole), and analgesics (paracetamol, and codeine phosphate). While some NMP providers were prescribing for patients with greater health needs, all NMP providers could be better utilised to reach more of these patients. Conclusions This study highlights that although the NMP service has been implemented in NZ, it has yet to become mainstream healthcare practice. This work provides a baseline to evaluate the NMP service moving forward and enable policy development. Improved implementation and integration of primary care NMP services can ensure continued access to prescribing services and medicines for our communities.

Description: Background The SARS-CoV-2 pandemic put a pressure on all healthcare professionals and has affected the delivery of health care services globally. There is a need to understand the impact on different health care professionals in different countries. The aim of the present study was to explore the psychological impact of the pandemic among dental staff in Norway in relation to background characteristics, work situation and preparedness of the service. Methods A structured questionnaire sent electronically to dentists, dental hygienists and dental assistants inquired information about the lockdown period in Norway (13 March-17 April 2020). Distributions of background characteristics, perceptions of preparedness and psychological impact were calculated. Exploratory factor analysis was performed, and Structural Equation Models (SEMs) were used to compare psychological impact between dental professionals treating patients versus not during lockdown. Results Among the 1237 respondents, 58.8% worked clinically with patients. The majority were concerned of becoming infected (71.9%), of infecting others (85.4%) and/or of their family becoming infected (76.9%). Respondents who treated patients felt significantly more insecure about whether having become infected or not. The minority felt discriminated (6.7%), worried about death (11.7%), felt that life was threatening (9.8%) or felt loss of control of their lives (8.9%). More than 80% agreed that their workplace handled the situation well. Four factors were retrieved from the factor analysis. SEMs showed that gender and work experience had a significant effect on the factors Instability, Infection and Concerns. Respondents with work experience ≥10 years were less likely to express fear about Instability and Infection. Personnel reporting that their workplace had adequate equipment were also less concerned, however having adequate equipment did not reduce the factor Loss of control. Conclusion The present study showed a considerable psychological impact of the COVID-19 pandemic on dental personnel in Norway regardless of working clinically with patients or not. However, working with patients increased the insecurity about own infection status and of infecting people close to them. A safe working environment and adequate infection control measures are associated with less fear of infection and feeling of instability.

Description: Background Adequate financing is a crucial function, securing that physical rehabilitation services (i.e., physiotherapy, occupational therapy, prosthetics and orthotics) are available with no financial hardship. Like many other countries, despite the adoption of various policies and strategies in recent decades, Iran enjoys no desirable physical rehabilitation financing (PRF). Accordingly, this qualitative study aimed to explore the PRF-related strategies and issues as well as their impacts on relevant policies in Iran. Methods An analysis of PRF-related policies was conducted in Iran using semi-structured interviews and policy documents review. Purposive and snowball sampling techniques were employed to select key informants, including health-policy makers, civil society, rehabilitation-policy makers, university professors, and practitioners. Thematic analysis was used to analyze the collected data. The analysis was framed within Kingdon’s multiple streams. Results The hindering factors for desirable financing were weak insurance coverage, lack of sustainable financial resources, fragmented financing, lack of split between provider and financer, high-cost of physical rehabilitation services, low engagement of relevant experts in policy-making processes, and corrupt activities. In the policy stream, the following factors were highlighted: involvement of sustainable financial resources, the use of external revenue sources, allocated resources’ earmarking, the integration of the current funds to have better pooling, the use of incentive and timely payment mechanisms, the implementation of strategic purchasing principals, and the employment of effective rationing strategies. Moreover, parliament support, changes in administrations, international effects, pressures from interest campaigns and NGOs, and international sanctions were found as factors affecting the politics stream. Conclusion The study findings revealed that a variety of national and international factors affect PRF-related issues in Iran. The recently enacted laws indicate that the PRF policies have already been on the national health political agenda. The study reflected the multifaceted nature of barriers to optimal PRF in Iran.

Description: Background More and more female residents enter postgraduate medical training (PGMT). Meanwhile, women are still underrepresented in academic medicine, in leadership positions and in most surgical specialties. This suggests that female residents’ career development may still be negatively impacted by subtle, often unconscious stereotype associations regarding gender and career-ambition, called implicit gender-career bias. This study explored the existence and strength of implicit gender-career bias in doctors who currently work in PGMT, i.e. in attending physicians who act as clinical trainers and in their residents. Methods We tested implicit gender-career bias in doctors working in PGMT by means of an online questionnaire and an online Implicit Association Test (IAT). We used standard IAT analysis to calculate participants’ IAT D scores, which indicate the direction and strength of bias. Linear regression analyses were used to test whether the strength of bias was related to gender, position (resident or clinical trainer) or specialty (non-surgical or surgical specialty). Results The mean IAT D score among 403 participants significantly differed from zero (D-score = 0.36 (SD = 0.39), indicating bias associating male with career and female with family. Stronger gender-career bias was found in women (βfemale =0 .11; CI 0.02; 0.19; p = 0.01) and in residents (βresident 0.12; CI 0.01; 0.23; p = 0.03). Conclusions This study may provide a solid basis for explicitly addressing implicit gender-career bias in PGMT. The general understanding in the medical field is that gender bias is strongest among male doctors’ in male-dominated surgical specialties. Contrary to this view, this study demonstrated that the strongest bias is held by females themselves and by residents, independently of their specialty. Apparently, the influx of female doctors in the medical field has not yet reduced implicit gender-career bias in the next generation of doctors, i.e. in today’s residents, and in females.

Description: Background HAK/KUP/KT (High-affinity K+ transporters/K+ uptake permeases/K+ transporters) is the largest potassium transporter family in plants, and plays pivotal roles in K+ uptake and transport, as well as biotic and abiotic stress responses. However, our understanding of the gene family in barley (Hordeum vulgare L.) is quite limited. Results In the present study, we identified 27 barley HAK/KUP/KT genes (hereafter called HvHAKs) through a genome-wide analysis. These HvHAKs were unevenly distributed on seven chromosomes, and could be phylogenetically classified into four clusters. All HvHAK protein sequences possessed the conserved motifs and domains. However, the substantial difference existed among HAK members in cis-acting elements and tissue expression patterns. Wheat had the most orthologous genes to barley HAKs, followed by Brachypodium distachyon, rice and maize. In addition, six barley HAK genes were selected to investigate their expression profiling in response to three abiotic stresses by qRT-PCR, and their expression levels were all up-regulated under salt, hyperosmotic and potassium deficiency treatments. Conclusion Twenty seven HAK genes (HvHAKs) were identified in barley, and they differ in tissue expression patterns and responses to salt stress, drought stress and potassium deficiency.

Description: Background Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. Methods Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. Results A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. Conclusions For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

Description: Background Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. Objectives To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). Methods Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. Results Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. Conclusion The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

Description: Background In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce. Results Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an ‘in house’ software-based approach which results in lower measured variability between mice. Conclusions Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.

Description: Background Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein. Methods Here, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization. Results HDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3β increases without any change in total GSK-3β level. Conclusions HDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.

Description: Background Simulated metagenomic reads are widely used to benchmark software and workflows for metagenome interpretation. The results of metagenomic benchmarks depend on the assumptions about their underlying ecosystems. Conclusions from benchmark studies are therefore limited to the ecosystems they mimic. Ideally, simulations are therefore based on genomes, which resemble particular metagenomic communities realistically. Results We developed Tamock to facilitate the realistic simulation of metagenomic reads according to a metagenomic community, based on real sequence data. Benchmarks samples can be created from all genomes and taxonomic domains present in NCBI RefSeq. Tamock automatically determines taxonomic profiles from shotgun sequence data, selects reference genomes accordingly and uses them to simulate metagenomic reads. We present an example use case for Tamock by assessing assembly and binning method performance for selected microbiomes. Conclusions Tamock facilitates automated simulation of habitat-specific benchmark metagenomic data based on real sequence data and is implemented as a user-friendly command-line application, providing extensive additional information along with the simulated benchmark data. Resulting benchmarks enable an assessment of computational methods, workflows, and parameters specifically for a metagenomic habitat or ecosystem of a metagenomic study. Availability Source code, documentation and install instructions are freely available at GitHub (https://github.com/gerners/tamock).

Description: Background Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng. Results Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress. Conclusions These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.

Description: Background The mechanism of egg formation in the oviduct of laying hens is tightly controlled; each segment of the oviduct contributes a unique component of the egg. Several genes/proteins are involved in the synthesis of a completely healthy egg. This implies a time- and tissue-specific expression of genes and proteins in the different oviductal segments. We used hens at different physiological stages and time points to understand the transcriptional regulation of egg-white (albumen) synthesis and secretion onto the eggs in the magnum of laying hens. This study used Next-Generation Sequencing and quantitative real-time PCR (qPCR) to detect the novel genes and the cognate biological pathways that regulate the major events during the albumen formation. Results Magnum tissues collected from laying (n = 5 each at 3 h post-ovulation, p.o. and 15–20 h p.o.), non-laying (n = 4), and molting (n = 5) hens were used for differential gene expression analyses. A total of 540 genes (152 upregulated and 388 down-regulated) were differentially expressed at 3 h p.o. in the magnum of laying hens. Kyoto Encyclopedia of Genes and Genomes pathways analysis of the 152 upregulated genes revealed that glycine, serine, and threonine metabolism was the most-enriched biological pathway. Furthermore, the top two most enriched keywords for the upregulated genes were amino-acid biosynthesis and proteases. Nine candidate genes associated with albumen formation were validated with qPCR to have differential expression in laying, non-laying, and molting hens. Proteases such as TMPRSS9, CAPN2, MMP1, and MMP9 (protein maturation, ECM degradation, and angiogenesis); enzymes such as PSPH, PHGDH, and PSAT1 (amino-acid biosynthesis); RLN3, ACE, and REN (albumen synthesis, secretion and egg transport); and AVD, AvBD11, and GPX3 (antimicrobial and antioxidants) were recognized as essential molecules linked to albumen deposition in the magnum. Conclusions This study revealed some novel genes that participate in the signaling pathways for egg-white synthesis and secretion along with some well-known functional genes. These findings help to understand the mechanisms involved in albumen biosynthesis.

Description: Background RNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step–such as alignment of reads to a reference genome–of a larger workflow. The demand for a more comprehensive and reproducible workflow has led to the production of a number of publicly available RNA-seq pipelines. However, we have found that most require computational expertise to set up or share among several users, are not actively maintained, or lack features we have found to be important in our own analyses. Results In response to these concerns, we have developed a Scalable Pipeline for Expression Analysis and Quantification (SPEAQeasy), which is easy to install and share, and provides a bridge towards R/Bioconductor downstream analysis solutions. SPEAQeasy is portable across computational frameworks (SGE, SLURM, local, docker integration) and different configuration files are provided (http://research.libd.org/SPEAQeasy/). Conclusions SPEAQeasy is user-friendly and lowers the computational-domain entry barrier for biologists and clinicians to RNA-seq data processing as the main input file is a table with sample names and their corresponding FASTQ files. The goal is to provide a flexible pipeline that is immediately usable by researchers, regardless of their technical background or computing environment.

Description: Background Leveraging previously identified viral interactions with human host proteins, we apply a machine learning-based approach to connect SARS-CoV-2 viral proteins to relevant host biological functions, diseases, and pathways in a large-scale knowledge graph derived from the biomedical literature. Our goal is to explore how SARS-CoV-2 could interfere with various host cell functions, and to identify drug targets amongst the host genes that could potentially be modulated against COVID-19 by repurposing existing drugs. The machine learning model employed here involves gene embeddings that leverage causal gene expression signatures curated from literature. In contrast to other network-based approaches for drug repurposing, our approach explicitly takes the direction of effects into account, distinguishing between activation and inhibition. Results We have constructed 70 networks connecting SARS-CoV-2 viral proteins to various biological functions, diseases, and pathways reflecting viral biology, clinical observations, and co-morbidities in the context of COVID-19. Results are presented in the form of interactive network visualizations through a web interface, the Coronavirus Network Explorer (CNE), that allows exploration of underlying experimental evidence. We find that existing drugs targeting genes in those networks are strongly enriched in the set of drugs that are already in clinical trials against COVID-19. Conclusions The approach presented here can identify biologically plausible hypotheses for COVID-19 pathogenesis, explicitly connected to the immunological, virological and pathological observations seen in SARS-CoV-2 infected patients. The discovery of repurposable drugs is driven by prior knowledge of relevant functional endpoints that reflect known viral biology or clinical observations, therefore suggesting potential mechanisms of action. We believe that the CNE offers relevant insights that go beyond more conventional network approaches, and can be a valuable tool for drug repurposing. The CNE is available at https://digitalinsights.qiagen.com/coronavirus-network-explorer.

Description: Background Percutaneous left atrial appendage (LAA) closure is an alternative to oral anticoagulation (OAC) for atrial fibrillation (AF) patients with high thromboembolism risk, particularly with contraindications to OAC. The LAA itself could possess proarrhythmogenic properties. As patients undergoing LAA closure could be candidates for cardioversion or ablation, we aimed to evaluate AF disease progression following LAA closure and the outcome of patients undergoing a rhythm control strategy after the procedure. Methods The prospective multicenter French Nationwide Observational LAA Closure Registry (FLAAC) comprises 33 French interventional cardiology departments. Patients were included if they fulfilled the following criteria: history of non-valvular AF, successful LAA closure and long-term ECG follow-up. Results A total of 331 patients with successful LAA closure were enrolled in the study. Patients mean age was 75.4 ± 0.5 years. The study population was characterized by a high thromboembolic risk (CHA2DS2-VASc score: 4.5 ± 0.1) and frequent comorbidities. The median follow-up was 11.9 months. One hundred and nineteen (36.0%) patients were in sinus rhythm (SR) at baseline. Among SR patients, documented AF was observed in 16 (13.4%) patients whereas 15 (7.1%) patients in AF at baseline restored SR, at the end of follow up. Finally, only 13 patients (4%) underwent procedures to restore SR without complications during the follow-up. Conclusions The vast majority of patients undergoing LAA closure have the same AF status at baseline and one year after the index procedure. During the follow-up, a very small proportion (4%) of our population underwent procedures to restore SR without complications whatever the post-procedural antithrombotic strategy was.

Description: Background Understanding the natural history of chronic hepatitis B (CHB) virus infection is important for determining optimal management and predicting prognosis in patients. The aim of this study was to determine the prevalence of different phases of CHB infection among Eritrean patients and to identify the proportion of patients who are eligible for treatment according to the latest American Association for the Study of Liver Diseases (AASLD) guidelines. Methods This cross-sectional study enrolled 293 CHB patients (213 males and 80 females) between Jan 2017 and Feb 2019. The patients were classified into immune-tolerant, immune-active, and inactive CHB phases of the infection, which is based on the results of Hepatitis B virus (HBV) serological panel (HBsAg, anti-HBc total, HBeAg, and anti-HBe), ALT levels, and HBV DNA viral load. The 2018 AASLD guidelines were also used to identify patients who needed treatment. Results The mean age of the patients was 41.66 ± 13.84 years. Of these, 3 (1.0%) were at the immune tolerant phase, 58 (19.8%) at the immune-active CHB phase, and 232 (79.2%) at the inactive CHB phase. As most subjects (93%) were HBeAg-negative, based on AASLD guidelines, only 5 (1.7%) were currently eligible for treatment. Conclusions Our data show that CHB patients in Eritrea were predominantly in the inactive CHB phase. Although initiating antiviral therapy is not recommended in these patients, periodic assessment of liver function and disease severity should be considered in patients older than 40 years. The immune-tolerant phase had the fewest patients, most of whom were aged above 20 years, attesting to the success of incorporating HBV vaccine in the national childhood immunization program since 2002. Our study shows that adopting AASLD treatment guidelines with adjustments to suit the local setting is a suitable option in the management of Eritrean CHB patients.

Description: Background Carnobacterium species are lactic acid-producing Gram-positive bacteria that have been approved by the US Food and Drug Administration and Health Canada for use as a food bio-preservative. The use of live bacteria as a food additive and its potential risk of infections in immunocompromised patients are not well understood. Case presentation An 81-year-old male with a history of metastatic prostate cancer on androgen deprivation therapy and chronic steroids presented to our hospital with a 2-week history of productive cough, dyspnea, altered mentation, and fever. Extensive computed tomography imaging revealed multifocal pneumonia without other foci of infection. He was diagnosed with pneumonia and empirically treated with ceftriaxone and vancomycin. Blood cultures from admission later returned positive for Carnobacterium inhibens. He achieved clinical recovery with step-down to oral amoxicillin/clavulanic acid for a total 7-day course of antibiotics. Conclusions This is the fourth reported case of bacteremia with Carnobacterium spp. isolated from humans. This case highlights the need to better understand the pathogenicity and disease spectrum of bacteria used in the food industry for bio-preservation, especially in immunocompromised patients.

Description: Background Prosthetic joint infections (PJI) are one of the most serious complication of arthroplasty. The management of PJI needs a multidisciplinary collaboration between orthopaedic surgeon, infectious disease specialist and microbiologist. In France, the management of PJI is organized around reference centres (CRIOACs). Our main objective was to perform an audit through a questionnaire survey based on clinical cases, to evaluate how French physicians manage PJI. Eligible participants were all physicians involved in care of patients presenting a PJI. Physicians could answer individually, or collectively during a multidisciplinary team meeting dedicated to PJI. The survey consisted as three questionnaires organized in a total of six clinical cases. Results Answers from the CRIOACs to the three questionnaires were 92, 77, and 53%. Between 32 and 39% of respondents did not administer antibiotic prophylaxis despite positive S. aureus pre-operative documentation. One-stage exchange strategy was widely preferred in all clinical cases, with no difference between CRIOACs and other centres. Rifampicin was prescribed for S. aureus PJI, in a situation with (90–92%) or without any prosthesis (70%). There was no consensus for the total antibiotic regimen duration, with prescriptions from six to 12 weeks for a majority of respondents. Conclusions Surgical strategy for the management of PJI was homogenous with a preference for a one-stage exchange strategy. Medical management was more heterogenous, which reflects the heterogeneity of those infections and difficulties to perform studies with strong conclusions.

Description: Background The effects of extreme temperature on infectious diseases are complex and far-reaching. There are few studies to access the relationship of pulmonary tuberculosis (PTB) with extreme temperature. The study aimed to identify whether there was association between extreme temperature and the reported morbidity of PTB in Shandong Province, China, from 2005 to 2016. Methods A generalized additive model (GAM) was firstly conducted to evaluate the relationship between daily reported incidence rate of PTB and extreme temperature events in the prefecture-level cities. Then, the effect estimates were pooled using meta-analysis at the provincial level. The fixed-effect model or random-effect model was selected based on the result of heterogeneity test. Results Among the 446,016 PTB reported cases, the majority of reported cases occurred in spring. The higher reported incidence rate areas were located in Liaocheng, Taian, Linyi and Heze. Extreme low temperature had an impact on the reported incidence of PTB in only one prefecture-level city, i.e., Binzhou (RR = 0.903, 95% CI: 0.817–0.999). While, extreme high temperature was found to have a positive effect on reported morbidity of PTB in Binzhou (RR = 0.924, 95% CI: 0.856–0.997) and Weihai (RR = 0.910, 95% CI: 0.843–0.982). Meta-analysis showed that extreme high temperature was associated with a decreased risk of PTB (RR = 0.982, 95% CI: 0.966–0.998). However, extreme low temperature was no relationship with the reported incidence of PTB. Conclusion Our findings are suggested that extreme high temperature has significantly decreased the risk of PTB at the provincial levels. The findings have implications for developing strategies to response to climate change.

Description: Background Hypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare. Case presentation Here we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range. Conclusions Mild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.

Description: Background Cardiovascular risk factors in Chinese ethnic minority groups are rarely reported. Objective To quantify the cardiovascular risk factors in Miao Chinese adults and to examine the association of health behaviors and metabolic risk factors with dyslipidemia. Methods A cross-sectional analysis was conducted using baseline data from the China Multi-Ethnic Cohort (CMEC) study. A representative sample of 5559 Miao participants aged 30 to 79 years were surveyed and given physical and laboratory exams. The proportion of behavioral and metabolic risk factors were described in ethnic Miao adults. Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between health behaviors and metabolic risk factors with dyslipidemia. Results In Miao Chinese adults, the prevalence of dyslipidemia was 32.8%. After multivariate adjustment, subjects with poor waist-to-hip ratio (WHR), body mass index (BMI), fasting blood glucose (FBG) and blood pressure (BP) were more likely to have higher risk of triglycerides (TG) abnormality, regardless of gender and age. Furthermore, the strongly association was detected between poor WHR and low density lipoprotein cholesterol (LDL-C) abnormality (adjusted OR = 5.24, 95%CI: 2.42–11.34) in the older subgroup (≥ 60 years). Males who current smoking were an independent risk factor only for high density lipoprotein cholesterol (HDL-C) abnormality (adjusted OR = 1.44, 95%CI: 1.05–1.99). However, in the subgroup age, current smoker were at greater risk of high TG and low HDL-C. Males with regular drinking were less likely to be high LDL-C (adjusted OR = 0.51, 95%CI: 0.32–0.81). Conclusions The present findings indicated that Miao adults with metabolic risk factors were at greater risk of dyslipidemia.

Description: Background Vector control is an essential component in prevention and control of malaria in malaria endemic areas. Insecticide treated nets is one of the standard tools recommended for malaria vector control. The objective of the study was to determine physical integrity and insecticidal potency of long-lasting insecticidal nets (LLINs) used in control of malaria vector in Kirinyaga County, Kenya. Method The study targeted households in an area which had received LLINs during mass net distribution in 2016 from Ministry of Health. A total of 420 households were sampled using systematic sampling method, where the household heads consented to participate in the study. A semi-structured questionnaire was administered to assess care and use while physical examination was used to determine integrity. Chemical concentration was determined by gas chromatography mass spectroscopy (GC-MS). Data analysis was done using Statistical Package for Social Sciences (SPSS) version 19. Results After 18 months of use, 96.9% (95% CI: 95.2–98.6%) of the distributed nets were still available. Regarding net utilization, 94.1% of household heads reported sleeping under an LLIN the previous night. After physical examination, 49.9% (95% CI: 43–52.8%) of the bed nets had at least one hole. The median number of holes of any size was 2[interquartile range (IQR) 1–4], and most holes were located on the lower part of the nets, [median 3 (IQR 2–5)]. Only 15% of the nets with holes had been repaired. The median concentration for α-cypermethrin was 7.15 mg/m2 (IQR 4.25–15.31) and 0.00 mg/g (IQR 0.00–1.99) for permethrin. Based on pHI, Chi-square test varied significantly with the manufacturer (X (6, N = 389) = 29.14, p = 0.04). There was no significant difference between nets with different number of washes (X2(2) = 4.55, p = 0.103). Conclusion More than three-quarters of the nets supplied had survived and insecticidal potency was adequate in vector control. Standard procedure for field evaluation of surface insecticidal content available to a mosquito after landing on a net to rest is recommended.

Description: Background The impact of the coronavirus disease (COVID-19) pandemic on wellbeing and health has so far been studied using mostly cross-sectional designs. To place recent findings into context, we compared symptoms and functional health status in two independent samples assessed before and during the COVID-19 pandemic. Methods Participants were recruited via an online panel using quota sampling. We assessed symptoms, functional health, and global quality of life with the EORTC QLQ-C30 in two general population samples in Spain (collected in July 2019 and April 2020). We also assessed several COVID-19 related variables, such as adherence to social distancing. Results Data from N = 1010 participants before the pandemic (mean age 47.1 years, 50.5% female) were compared with data from N = 504 participants during the pandemic (mean age 47.1 years, 50.8% female). Participants during the pandemic (vs. before the pandemic) reported lower role functioning and emotional functioning, as well as less symptom burden. A lower degree of social distancing was associated with better functional health and lower symptom burden. Conclusion Our findings indicate an impact of the COVID-19 pandemic on functional health and symptom burden in the Spanish general population. The comparison of before and during the pandemic can be used to benchmark results raised only during the pandemic.

Description: Background The coronavirus disease of 2019 (COVID-19) has quickly spread to all corners of the world since its emergence in Wuhan, China in December of 2019. The disease burden has been heterogeneous across regions of the world, with Americas leading in cumulative cases and deaths, followed by Europe, Southeast Asia, Eastern Mediterranean, Africa and Western Pacific. Initial responses to COVID-19 also varied between governments, ranging from proactive containment to delayed intervention. Understanding these variabilities allow high burden countries to learn from low burden countries on ways to create more sustainable response plans in the future. Methods This study used a mixed-methods approach to perform cross-country comparisons of pandemic responses in the United States (US), Brazil, Germany, Australia, South Korea, Thailand, New Zealand, Italy and China. These countries were selected based on their income level, relative COVID-19 burden and geographic location. To rationalize the epidemiological variability, a list of 14 indicators was established to assess the countries’ preparedness, actual response, and socioeconomic and demographic profile in the context of COVID-19. Results As of 1 April 2021, the US had the highest cases per million out of the nine countries, followed by Brazil, Italy, Germany, South Korea, Australia, New Zealand, Thailand and China. Meanwhile, Italy ranked first out of the nine countries’ total deaths per million, followed by the US, Brazil, Germany, Australia, South Korea, New Zealand, China and Thailand. The epidemiological differences between these countries could be explained by nine indicators, and they were 1) leadership, governance and coordination of response, 2) communication, 3) community engagement, 4) multisectoral actions, 5) public health capacity, 6) universal health coverage, 7) medical services and hospital capacity, 8) demography and 9) burden of non-communicable diseases. Conclusion The COVID-19 pandemic manifests varied outcomes due to differences in countries’ vulnerability, preparedness and response. Our study rationalizes why South Korea, New Zealand, Thailand, Australia and China performed better than the US, Italy and Brazil. By identifying the strengths of low burden countries and weaknesses of hotspot countries, we elucidate factors constituting an effective pandemic response that can be adopted by leaders in preparation for re-emerging public health threats.

Description: Background One public health problem that cannot be ignored is the mental health of left-behind elderly individuals in rural areas. However, the burden of care and parenting stress among left-behind elderly individuals has never been analyzed. The purpose of this study was to explore the level of caregiver burden and parenting stress and their relationship among left-behind elderly individuals. Methods A total of 261 left-behind elderly people responded to the study. The 22-item Zarit Burden Interview and the 36-item Parenting Stress Index-Short Form were used. Results We sent out 300 questionnaires in total. The effective rate was 87% (n = 261). Among the left-behind elderly individuals, most respondents were female (n = 171; 65.5%). The results showed that older age (OR:3.04; 95%CI: 1.307–7.048), an annual income of ¥5000–¥9900 (OR:3.25; 95%CI: 1.192–8.852) and higher parenting stress (OR:1.17; 95%CI: 1.103–1.242) were the risk factors related to higher caregiver burden in the left-behind elderly individuals. The influencing factor for lower caregiver burden in the left-behind elderly was gender (being male) (OR:0.08; 95%CI:0.036–0.178). Age (r = − 0.789; P 

Description: Background There is an expected increase in heatwaves globally. As such, it is imperative to have sufficient levels of heatwave-protective knowledge and behaviour in areas regularly affected by heatwaves. Our study assessed this among urban populations in Tunisia, Georgia and Israel. Methods We undertook a cross-sectional population survey in the three countries. The questionnaire focused on obtaining information on respondents’ knowledge level regarding 1) symptoms due to overheating, 2) risk groups for heatwaves, 3) actions to take when someone is overheated, and 4) heatwave-protective measures. Furthermore, we asked respondents about protective measures they applied during the last heatwave. We compared the results between the countries. Results Heatwave-protective knowledge was highest in Israel, and lowest in Georgia, for all indicators except for heatwave-protective measures, for which knowledge was highest in Tunisia. Most respondents who named certain protective measures had also applied these during the last heatwave: more than 90% for all measures except for one in Tunisia and Israel, and more than 80% for all measures in Georgia. Conclusion There is a need to further improve heatwave-protective knowledge in Tunisia, Georgia and Israel. One potential solution to achieve this is by implementing a National Heat Health Action Plan. Improving knowledge is a vital step before adaptive behaviour can take place.

Description: Background The objective of the present micro-computed tomography (micro-CT) study was to assess the presence of voids in band-shaped isthmuses obturated using three different filling techniques. Methods Twenty-four artificial molar teeth with a band-shaped isthmus were allocated to three groups (n = 8) for obturation, according to the filling technique: single-cone (SC), continuous wave of condensation (CWC) or lateral condensation (LC). Obturation was performed with gutta-percha (GP) cones and iRoot SP (Innovative Bioceramix, Vancouver, Canada). Post-filling micro-CT scanning was performed. The percentage of filling materials and void volumes were calculated in the isthmus areas and data were analyzed using one-way ANOVA and Tukey tests. Results The mean percentage of void volumes and corresponding filling percentages in the isthmus areas after obturation in the SC groups was 22.98 % ± 1.19 %, 77.02 % ± 1.19 %; in the CWC groups 10.46 % ± 2.28 %, 89.54 % ± 2.28 %; and in the LC groups was 13.14 % ± 1.85 %, 86.86 % ± 1.85 %, respectively. Conclusions In band-shaped isthmus area, the obturation quality of CWC was superior to SC and LC techniques.

Description: Background Bulbar urethral stricture is a common cause for urinary symptoms in men and its two main treatment options both have drawbacks with little evidence on their relative cost-effectiveness. Current guidelines on the management of recurrent bulbar urethral stricture have been predominantly based on expert opinion and panel consensus. Objective To assess the relative cost-effectiveness of open urethroplasty and endoscopic urethrotomy as treatment for recurrent urethral stricture in men. Methods Set in the UK National Health Service with recruitment from 38 hospital sites, a randomised controlled trial of open urethroplasty and endoscopic urethrotomy with 6-monthly follow-up over 24 months was conducted. Two hundred and twenty-two men requiring operative treatment for recurrence of bulbar urethral stricture and having had at least one previous intervention for stricture were recruited. Effectiveness was measured by quality- adjusted life years (QALYs) derived from EQ-5D 5L. Cost-effectiveness was measured by the incremental cost per QALY gained over 24 months using a within trial analysis and a Markov model with a 10-year time horizon. Results In the within trial, urethroplasty cost on average more than urethrotomy (cost difference: £2148 [95% CI 689, 3606]) and resulted in a similar number of QALYs on average (QALY difference: − 0.01 [95% CI − 0.17, 0.14)] over 24 months. The Markov model produced similar results. Sensitivity analyses using multiple imputation, suggested that the results were robust, despite observed missing data. Conclusions Based on current practice and evidence, urethrotomy is a cost-effective treatment compared with urethroplasty. Keypoints Urethrotomy and urethroplasty both led to symptom improvement for men with bulbar urethral stricture—a common cause for urinary symptoms in men; Urethroplasty appeared unlikely to offer good value for money compared to urethrotomy based on current evidence. Trial registration: ISRCTN: 98009168 (date: 29 November 2012) and it is also in the UK NIHR Portfolio (reference 13507). Trial protocol: The latest version (1.8) of the full protocol is available at: www.journalslibrary.nihr.ac.uk/programmes/hta/105723/#/ and a published version is also available: Stephenson R, Carnell S, Johnson N, Brown R, Wilkinson J, Mundy A, et al. Open urethroplasty versus endoscopic urethrotomy—clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial. Trials 2015;16:600. https://doi.org/10.1186/s13063-015-1120-4. Trial main clinical results publication: Goulao B, Carnell S, Shen J, MacLennan G, Norrie J, Cook J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial), European Urology, Volume 78, Issue 4, 2020, Pages 572–580.

Description: Background A Case Difficulty Assessment Form was designed for use in endodontic curricula, and to assist practitioners with treatment planning, referral and recording. The aim of this study was to determine how endodontic case difficulty factors influence the operating time of single-visit nonsurgical endodontic treatments under general anesthesia. Methods Data on 198 single-visit endodontic treatments (80 anterior teeth, 43 premolars, and 75 molars) performed under general anesthesia by a specialized practitioner were obtained from 119 special needs patients (mean [SD] age = 30.7 [14.7] years). Total duration of operation was analyzed with relation to demographic and dental factors and American Association of Endodontists (AAE) Case Difficulty Assessment factors. Mann–Whitney U test, t-test, and Kruskal–Wallis test were used to assess relationships between operating time and confounding factors (p 

Description: Background It is important to know the biomechanical properties of an allograft. This is because when looking to do a transplant of a tendon, the tendon must have very similar biomechanical properties to the original tendon. To use tendon allografts, it is critical to properly sterilize the tendon before implantation. In past decades, several sterilization procedures have been used. This study aimed to systematically evaluate the existing literature to compare the values of failure load/ultimate strength and Young’s modulus of elasticity of different sterilization methods on commonly used tendon allografts. Five major scientific literature databases (Web of Science, Science Direct, Scopus, PLOS ONE, Hindawi) and additional sources were used. Results Studies used had to show a particular sterilization method. Studies were identified to meet the following inclusion criteria: is a controlled laboratory study, gamma irradiation (dose reported), and other sterilization methods. Search for publications dated between 1991 and March 31st, 2020. The database search and additional sources resulted in 284 records. Two hundred thirty records eliminated during the screening for various reasons. The number of articles used in the final synthesis was 54. Conclusions Identified sterilization methods (gamma irradiation, ethylene oxid, supercritical carbon dioxide (SCCO2), BioCleanse, Electron Beam) are offered as a catalog of potential methods. As a result of the broadness of the present research, it provides an overview of sterilization methods and their effect on the mechanical properties (failure load and Young’s modulus of elasticity) of tendons. It does not stand for the state-of-the-art of any single process. Based on a systematic literature review, we recommend freezing and gamma irradiation or electron beam at 14.8–28.5 kGy. These methods are effective at keeping or improving the mechanical properties, while fully sterilizing the inside and the outside of the tendon. Other sterilization method (ethylene oxide, supercritical carbon dioxide (SCCO2), BioCleanse) deteriorated the mechanical properties. These methods are not recommended.

Description: Background Transbronchial lung biopsy (TBLB) in the diagnosis of lymphangioleiomyomatosis (LAM) is not a common approach, although TBLB is often performed in diffuse lung diseases. We aimed to examine the diagnostic value and safety of TBLB in LAM patients based on the data collected in our center. Methods We reviewed LAM patients registered in our LAM Clinic from December 8, 2006, to December 31, 2019. All patients with definite or probable diagnosis of LAM who had been examined using TBLB were included. All available pathology slides were reviewed by an experienced LAM pathologist. All complications were reviewed by the medical records and confirmed using telephone interviews. Results The pathology results of 86 patients (including 74 definite LAM and 12 probable LAM) were available. The positive rate of TBLB in LAM patients was 49/86 (57.0%). The positive rates of SMA, HMB-45, ER, and PR in LAM patients were 97.6%, 93%, 84.6%, and 78.4% respectively. The positive rate of TBLB was 40%, 60% and 60.8% in patients with CT Grade I, Grade II, and Grade III respectively, and the difference was not significant. Patients who had 3–4 or 5–6 biopsied specimens had a higher rate of diagnosis than those with 1–2 biopsied specimens. Four patients (5.6%) reported pneumothorax. No major hemoptysis was reported. Conclusions TBLB is a feasible and safe procedure for obtaining a pathological diagnosis of LAM. Taking more than 2 samples during the biopsy procedure increased the rate of diagnosis.

Description: Background There has been a limited number of reports on the significance and risk factors of urethrovesical anastomotic urinary leakage (AUL) following robot-assisted radical prostatectomy (RARP). We aimed to analyze the clinical significance of AUL and evaluated its risk factors. Methods We conducted a multi-institutional study to review patients with prostate cancer undergoing RARP in three centers (The University of Tokyo Hospital, Mitsui Memorial Hospital, and Chiba Tokushukai Hospital). “Positive AUL” was defined as urinary extravasation at the anastomosis detected by post-operative cystogram and was further categorized into minor or major AUL. Univariate and multivariate analyses were performed to identify predictors of AUL. Postoperative continence rates and time to achieve continence were also analyzed. Results A total of 942 patients underwent RARP for prostate cancer in 3 centers. Of these patients, a cystogram after the RARP procedure was not performed in 26 patients leaving 916 patients for the final analysis. AUL was observed in 56 patients (6.1%); 34 patients (3.7%) with minor AUL and 22 patients (2.4%) with major AUL. Patients with major AUL exhibited a significantly longer time to achieve continence than those without major AUL. Multivariate analysis demonstrated that longer console time (≥ 184 min) was significantly associated with overall AUL, and higher body mass index (≥ 25 g/kg2) was a significant predictor of both major and overall AUL. Conclusions The presence of major AUL was associated with the achievement of urinary continence, suggesting clinical relevance of its diagnosis by postoperative cystogram. A selective cystogram has been proposed for high-risk cases. Furthermore, identification of the risk factors of AUL will lead to optimal application.

Description: Background Ramie degumming is often carried out at high temperatures; therefore, thermostable alkaline pectate lyase (PL) is beneficial for ramie degumming for industrial applications. Thermostable PLs are usually obtained by exploring new enzymes or reconstructing existing enzyme by rational design. Here, we improved the thermostability of an alkaline pectate lyase (PelN) from Paenibacillus sp. 0602 with rational design and structure-based engineering. Results From 26 mutants, two mutants of G241A and G241V showed a higher thermostability compared with the wild-type PL. The mutant K93I showed increasing specific activity at 45 °C. Subsequently, we obtained combinational mutations (K93I/G241A) and found that their thermostability and specific activity improved simultaneously. The K93I/G241A mutant showed a half-life time of 15.9 min longer at 60 °C and a melting temperature of 1.6 °C higher than those of the wild PL. The optimum temperature decreased remarkably from 67.5 °C to 60 °C, accompanied by a 57% decrease in Km compared with the Km value of the wild-type strain. Finally, we found that the intramolecular interaction in PelN was the source in the improvements of molecular properties by comparing the model structures. Rational design of PelN was performed by stabilizing the α-helices with high conservation and increasing the stability of the overall structure of the protein. Two engineering strategies were applied by decreasing the mutation energy calculated by Discovery Studio and predicting the free energy in the process of protein folding by the PoPMuSiC algorithm. Conclusions The results demonstrated that the K93I/G241A mutant was more suitable for industrial production than the wild-type enzyme. Furthermore, the two forementioned strategies could be extended to reveal engineering of other kinds of industrial enzymes.

Description: Background Appendectomy for acute appendicitis is the most common procedure performed emergently by general surgeons in the United States. The current management of acute appendicitis is increasingly controversial as non-operative management gains favor. Although rare, appendiceal neoplasms are often found as an incidental finding in the setting of appendectomy. Criteria and screening for appendiceal neoplasms are not standardized among surgical societies. Methods The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients who underwent appendectomy over a 9-year period (2010–2018). Over the same time period, patients who underwent appendectomy in two municipal hospitals in The Bronx, New York City, USA were reviewed. Results We found a 1.7% incidence of appendiceal neoplasms locally and a 0.53% incidence of appendiceal tumors in a national population sample. Both groups demonstrated an increased incidence of appendiceal carcinoma by age. This finding was most pronounced after the age of 40 in both local and national populations. In our study, the incidence of appendiceal tumors increased with each decade interval up to the age of 80 and peaked at 2.1% in patients between 70 and 79 years. Conclusions Appendiceal adenocarcinomas were identified in patients with acute appendicitis that seem to be associated with increasing age. The presence of an appendiceal malignancy should be considered in the management of older patients with acute appendicitis before a decision to embark on non-operative therapy.

Description: Background Acute decompensated heart failure (ADHF) contributes millions of emergency department (ED) visits and it is associated with high in-hospital mortality. The aim of this study was to develop and validate a multiparametric score for critically-ill ADHF patients. Methods In this single-center, retrospective study, a total of 1268 ADHF patients in China were enrolled and divided into derivation (n = 1014) and validation (n = 254) cohorts. The primary endpoint was any in-hospital death, cardiac arrest or utilization of mechanical support devices. Logistic regression model was preformed to identify risk factors and build the new scoring system. The assigning point of each parameter was determined according to its β coefficient. The discrimination was validated internally using C statistic and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test. Results We constructed a predictive score based on six significant risk factors [systolic blood pressure (SBP), white blood cell (WBC) count, hematocrit (HCT), total bilirubin (TBIL), estimated glomerular filtration rate (eGFR) and NT-proBNP]. This new model was computed as (1 × SBP  9.2 × 109/L) + (1 × HCT ≤ 0.407) + (2 × TBIL 〉 34.2 μmol/L) + (2 × eGFR 

Description: Background Salivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response. Methods Venous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive. Results In asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone. Conclusions Despite their status as ‘current standard’ for COVID-19 testing, these findings highlight limitations of PCR-based tests.

Description: Background Terminal illness can cause a financial burden for many households. In England and Wales, fast-track access to welfare payments is available through special rules for the terminally ill (SRTI). Individuals are eligible for SRTI if they are judged to have 6 months or less to live. This criterion has been criticised as lacking a clinical basis, and being unfair for people with conditions where life-expectancy is difficult to accurately assess. Aim To conduct a budget impact analysis on the possible increase in expenditure of personal independence payments (PIP) following a change in England and Wales to SRTI so that everyone with a terminal illness is eligible. Methods The fraction of individuals with a given long-term condition was estimated by combining data from the Health Survey for England, the Office for National Statistics (ONS) and the Department for Work and Pensions. Logistic growth modelling and ONS population projections were used to project PIP expenditure from 2020 to 2025. The increased expenditure was calculated for hypothetical scenarios which may occur following an SRTI regime change, specifically an increase of 1, 2 and 3 percentage points in the fraction of individuals claiming PIP under SRTI. Data from the literature on the projected prevalence of mild, moderate and severe dementia was used to calculate the cost if everyone with a given severity of dementia claimed PIP under SRTI. Results Under the current SRTI regime, PIP expenditure under SRTI was projected to increase from £0.231bn in 2020 to £0.260bn in 2025, compared to equivalent figures of £11.1bn and £12.7bn under non-SRTI. Expenditure in 2025 following an increase in the fraction claiming of 1, 2 and 3 percentage points was projected to be £1.1bn, £1.9bn and £2.7bn respectively. In 2025, PIP expenditure was estimated to be £7.4bn if everyone with dementia claimed under SRTI, compared to £6.4bn if only individuals with moderate and severe dementia claimed, and £4.7bn if only individuals with severe dementia claimed. Conclusion Changes in SRTI are projected to lead to increases in PIP expenditure. However, the increased cost is small compared to expenditure under non-SRTI, especially as the highest costs were associated with extreme scenarios.

Description: Background Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. Methods The data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2). Results Although LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001). Conclusions FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

Description: Background Prosthetic joint infection (PJI) is one of the most feared complications following total arthroplasty surgeries. Gram-positive bacteria are the most common microorganisms implicated in PJIs, while infections mediated by fungi only account for 1% of cases. When dealing with PJIs, a two-stage revision arthroplasty is widely used. Briefly, a spacer is introduced until re-implantation of the definitive prosthesis to provide skeleton stabilization while delivering antibiotics in the site of the infection. Sometimes, antimicrobial therapy may fail, but the isolation of a second microorganism from the spacer is uncommon and even less frequent that of a yeast. Case presentation Here is described a case of a 75-year-old woman who underwent two-stage revision surgery of the left hip prosthesis secondary to a Staphylococcus capitis infection, whose spacer was found to be infected by Candida albicans at a later time. Briefly, the patient underwent revision surgery of the hip prosthesis for a suspected PJI. After the debridement of the infected tissue, an antibiotic-loaded spacer was implanted. The microbiological analysis of the periprosthetic tissues and the implant depicted a S. capitis infection that was treated according to the antimicrobial susceptibility profile of the clinical isolate. Three months later, the patient was admitted to the emergency room due to local inflammatory signs. Synovial fluid was sent to the laboratory for culture. No evidence of S. capitis was detected, however, a yeast was identified as Candida albicans. Fifteen days later, the patient was hospitalized for the removal of the infected spacer. Microbiological cultures confirmed the results of the synovial fluid analysis. According to the susceptibility profile, the patient was treated with fluconazole (400 mg/day) for 6 months. Seven months later, the patient underwent second-stage surgery. The microbiological tests on the spacer were all negative. After 12 months of follow-up, the patient has fully recovered and no radiological signs of infection have been detected. Conclusions Given the exceptionality of this complication, it is important to report these events to better understand the clinical outcomes after the selected therapeutic options to prevent and forestall the development of either bacterial or fungal spacer infections.

Description: Background Dental caries is the most prevalent non-communicable health condition globally. The surface-based susceptibility hierarchy indicates that surfaces in the same group have similar susceptibility to caries, where the most susceptible group consists of occlusal surfaces of first molars and buccal surfaces of lower first molars, and the least susceptible surfaces are smooth and proximal surfaces of first premolars, canines and incisors. Therefore, fluoride in the drinking water could impact one group more than the other group. The present study examined the association between fluoride levels in the drinking water and dental caries experience in adults in the context of varying tooth surface susceptibility. Methods Data from the cross-sectional National Lithuanian Oral Health Survey conducted in 2017–2019 included a stratified random sample of 1398 35–74-year-olds (52% response rate). Dental caries experience in dentine was measured at a surface level. The surfaces were grouped according to their caries susceptibility (group 1 being the most and group 4 the least susceptible), and dental caries experience was calculated separately for each susceptibility group, creating four outcomes. Information about explanatory variable, fluoride levels in the drinking water, was provided by the water suppliers. The questionnaire inquired about potential determinants: sociodemographic characteristics and oral health-related behaviors. Chi-square, Mann–Whitney U and Kruskal Wallis tests were used for descriptive statistics, and linear regression analyses to examine the association between fluoride levels and four outcomes. Results The proportions of median decayed, missing, filled surfaces decreased following the surface-based susceptibility hierarchy (group 1–33%, group 2–28%, group 3–24%, group 4–15%). When adjusted for potential determinants, higher-level fluoride (≥ 0.7 ppm vs

Description: Background Hospitals and healthcare institutions should be observant of the ever-changing environment and be adaptive to learning practices. By adopting the steps and other components of organizational learning, healthcare institutions can convert themselves into learning organizations and ultimately strengthen the overall healthcare system of the country. The present study aimed to examine the influence of several organizational learning dimensions on organization culture in healthcare settings during the COVID-19 outbreak. Methods During COVID-19 crisis in 2020, an online cross-sectional study was performed. Data were collected via official emails sent to 1500 healthcare professionals working in front line at four sets of hospitals in Saudi Arabia. Basic descriptive analysis was constructed to identify the variation between the four healthcare organizations. A multiple regression was employed to explore how hospitals can adopt learning process during pandemics, incorporating several Dimensions of Learning Organizations Questionnaire (DLOQ) developed by Marsick and Watkins (2003) and Leufvén and others (2015). Results Organizational learning including system connections (M = 3.745), embedded systems (M = 3.732), and team work and collaborations (M = 3.724) tended to have major significant relationships with building effective learning organization culture. Staff empowerment, dialogues and inquiry, internal learning culture, and continuous learning had the lowest effect on building health organization culture (M = 3.680, M = 3.3.679, M = 3.673, M = 3.663, respectively). A multiple linear regression was run to predict learning organization based on the several variables. These variables statistically significantly predicted learning organization, F (6, 1124) = 168.730, p