CaRLO

Description: Heme oxygenase (HO) is one of the cytoprotective enzymes that can mitigate the effects of oxidative stress. Here, we found that the ho mRNA level oscillates in the brain of Drosophila melanogaster with two minima at the beginning of the day and night. This rhythm was partly masked by light as its pattern changed in constant darkness (DD). It followed a similar trend in the clock mutant per01 under light/dark regime (LD12:12); however, differences between time points were not statistically significant. In older flies (20 days old), the rhythm was vanished; however, 15 days of curcumin feeding restored this rhythm with an elevated ho mRNA level at all time points studied. In addition, flies exposed to paraquat had higher ho expression in the brain, but only at a specific time of the day which can be a protective response of the brain against stress. These findings suggest that the expression of ho in the fly’s brain is regulated by the circadian clock, light, age, exposure to stress, and the presence of exogenous antioxidants. We also found that HO cross-talks with apoptosis and autophagy under different conditions. Induction of neuronal ho was accompanied by increased transcription of apoptosis and autophagy-related genes. However, this trend changed after exposure to curcumin and paraquat. Our results suggest that HO is involved in the control of apoptotic and autophagic key processes protecting the brain against oxidative damage.

Description: Perirenal adipose tissue, one of the fat masses surrounding the kidneys, can be obtained from healthy donors during a kidney transplant. Perirenal adipose tissue has only ever been known as a connective tissue to protect the kidneys and renal blood vessels from external physical stimulation. Yet, recently, as adipose tissue has begun to be considered an endocrine organ, and perirenal adipose tissue is now regarded to have a direct effect on metabolic diseases. The characteristics of perirenal adipose tissue from a healthy donor are that: (1) There are a large number of brown adipose cells (70–80% of the total), (2) Most of the brown adipose cells are inactive in the resting cell cycle, (3) Activating factors are constant low-temperature exposure, hormones, metastasis factors, and environmental factors, (4) Anatomically, a large number of brown adipose cells are distributed close to the adrenal glands, (5) Beige cells, produced by converting white adipocytes to brown-like adipocytes, are highly active, (6) Activated cells secrete BATokines, and (7) Energy consumption efficiency is high. Despite these advantages, all of the perirenal adipose tissue from a healthy donor is incinerated as medical waste. With a view to its use, this review discusses the brown adipocytes and beige cells in perirenal adipose tissue from a healthy donor, and proposes opportunities for their clinical application.

Description: The purpose of this study was to evaluate the effect of full-fat almonds (FFA) as an alternative protein and fat source for broiler feed on broiler productivity, nutrient digestibility, blood characteristics, cecal-fecal microflora, and foot-pad dermatitis (FPD). A total of 96, one-day-old broiler chickens (Arbor Acres) with initial body weight 41.61 ± 0.36 g were placed in 16 cages. In each trial, four treatments were set up: a basal diet partially replacing animal fat with FFA 0% (Control, CON), a basal diet partially replacing animal fat with FFA 1% (T1), a basal diet partial replacing animal fat with FFA 2% (T2), a basal diet partially replacing animal fat with FFA 4% (T3). The experiment was conducted for a total of 4 weeks. Feed conversion ratio (FCR) was higher (p 〈 0.05) in the T3 group of broilers at weeks 0 to 1 than in the CON group of broilers. From weeks 3 to 4, and for the entire experimental period, FCR was lower (p 〈 0.05) in the T3 group of broilers than in the CON and T1 groups of broilers. The apparent ileal digestibility (AID) of the ether extract (EE) was higher (p 〈 0.05) in the T3 group than in the other treatment groups, and AID of crude protein (CP) was higher (p 〈 0.05) in the T3 group than in the CON group. The apparent total tract digestibility (ATTD) of EE was lower (p 〈 0.05) in the CON group than in the other treatment groups, and the ATTD of CP and energy was higher (p 〈 0.05) in the T3 group of broilers than in the CON group of broilers. The AID and ATTD of total amino acids were higher (p 〈 0.05) in the T3 group than in the other treatment groups. Blood cholesterol levels were lower (p 〈 0.05) in the T3 group of broilers than in the CON and T1 groups of broilers, and higher (p 〈 0.05) in the CON group of broilers than in the T2 and T3 groups of broilers. The amount of E. coli in the cecal and fecal was lower (p 〈 0.05) in the T3 group than in CON and T1 groups. FPD score was higher (p 〈 0.05) in the T3 group of broilers than in the CON group of broilers. In conclusion, replacing a partial of animal fat with at least 4% FFA in broiler diets can increase growth performance and nutrient digestibility in broiler nutrition.

Description: The growing availability of mobile devices has lead to an arising development of smart cities services that share a huge amount of (personal) information and data. Without accurate and verified management, they could become severe back-doors for security and privacy. In this paper, we propose a smart city infrastructure able to integrate a distributed privacy-preserving identity management solution based on attribute-based credentials (p-ABC), a user-centric Consent Manager, and a GDPR-based Access Control mechanism so as to guarantee the enforcement of the GDPR’s provisions. Thus, the infrastructure supports the definition of specific purpose, collection of data, regulation of access to personal data, and users’ consents, while ensuring selective and minimal disclosure of personal information as well as user’s unlinkability across service and identity providers. The proposal has been implemented, integrated, and evaluated in a fully-fledged environment consisting of MiMurcia, the Smart City project for the city of Murcia, CaPe, an industrial consent management system, and GENERAL_D, an academic GDPR-based access control system, showing the feasibility.

Description: Limited therapeutic tools and an overwhelming clinical demand are the major limiting factors in pediatric obesity management. The optimal protocol, environment, body mass index (BMI) change targets and duration of obesity-oriented interventions remain to be elucidated. Aims: We aimed to characterize the singularities of follow-up, anthropometric and metabolic evolution of a large cohort of pediatric patients with obesity in a specialized university hospital outpatient obesity unit. Patients and methods: Follow-up duration (up to seven years), attrition rate and anthropometric and metabolic evolution of 1300 children and adolescents with obesity were studied. An individualized analysis was conducted in patients attaining a high level of weight loss (over 1.5 BMI-SDS (standard deviation score) and/or 10% of initial weight; n = 252; 19.4%) as well as in “metabolically healthy” patients (n = 505; 38.8%). Results: Attrition rate was high during the early stages (11.2% prior to and 32.5% right after their initial metabolic evaluation). Mean follow-up time was 1.59 ± 1.60 years (7% of patients fulfilled 7 years). The highest BMI reduction occurred in the first year (−1.11 ± 0.89 SDS, p 〈 0.001 in 72.5% of patients). At the end of the follow-up, improvements in glucose and lipid metabolism parameters were observed (both p 〈 0.05), that were highest in patients with the greatest weight reduction (all p 〈 0.01), independent of the time spent to achieve weight loss. The pubertal growth spurt negatively correlated with obesity severity (r = −0.38; p 〈 0.01) but patients attaining adult height exceeded their predicted adult height (n = 308, +1.6 ± 5.4 cm; p 〈 0.001). “Metabolically healthy” patients, but with insulin resistance, had higher blood pressure, glucose, uric acid and triglyceride levels than those without insulin resistance (all p 〈 0.05). Preservation of the “metabolically healthy” status was associated with BMI improvement. Conclusions: Behavioral management of children with obesity can be effective and does not impair growth but is highly conditioned by high attrition. The best results regarding BMI reduction and metabolic improvement are achieved in the first year of intervention and can be preserved if follow-up is retained.

Description: The development of nitrite-free meat products is a current industrial concern. Many efforts have been attempted to replace the nitrite effect in cured meats colour formation and pathogens control. Our previous work evidenced that lactic acid and a cold ripening were the best hurdle technologies for nitrite-free fermented sausages from metabolomics. In the first part of this work, we investigated the effect of lactic acid compared with both two alternative additives (glucono-D-lactone and a mix of sodium di-acetate/sodium lactate) and with low-nitrite sausages, all of them following either cold or traditional ripening. For this purpose, microbiological analysis, pH, water activity (aw), and a sensory study were performed. All nitrite-free sausages (cold or traditional ripened) showed quality and safety traits similar to low-nitrite traditionally ripened ones used as control. In addition, sensory study revealed that sausages with lactic acid were the most preferred cold ripened samples, supporting that this is an optimal strategy for the production of nitrite-free sausages. We selected this product for further studies. Indeed, in the second part, we evaluated the impact of ripening, and other hurdle technologies as High Pressure Processing (HPP) and under-vacuum storage against Listeria innocua and Salmonella spp. by a challenge test. Maximal declines were obtained for ripening along with HPP (i.e., 4.74 and 3.83 log CFU/g for L. innocua and Salmonella spp., respectively), suggesting that HPP might guarantee nitrite-free sausages safety. Although the quality of raw materials remains essential, these hurdle strategies largely contributed to nitrite-free sausages safety, offering a promising tool for the meat industry.

Description: Stripping crystallization (SC) was introduced in this work to purify p-chlorophenol from the p-chlorophenol-rich liquid mixture and to purify m-chlorophenol from the m-chlorophenol-rich liquid mixture, respectively. Essentially, SC combines melt crystallization and vaporization to produce the solid product and the vapor from a liquid mixture via a series of three-phase transformations at reduced pressures during the cooling process. At the end of the SC, only the solid product remained while the liquid mixture was almost eliminated and the produced vapor was removed. A set of differential equations based on the mass and energy balances were proposed to determine the incremental variations of the amounts of remaining liquid, produced solid and produced vapor during the batch SC process. The experimental yield and product purity of the final product obtained from the batch SC experiments were compared with those predicted by the model.

Description: Ovarian cancer remains as one of the most lethal gynecological cancers to date, with major challenges associated with screening, diagnosis and treatment of the disease and an urgent need for new technologies that can meet these challenges. Nanomaterials provide new opportunities in diagnosis and therapeutic management of many different types of cancers. In this review, we highlight recent promising developments of nanoparticles designed specifically for the detection or imaging of ovarian cancer that have reached the preclinical stage of development. This includes contrast agents, molecular imaging agents and intraoperative aids that have been designed for integration into standard imaging procedures. While numerous nanoparticle systems have been developed for ovarian cancer detection and imaging, specific design criteria governing nanomaterial targeting, biodistribution and clearance from the peritoneal cavity remain key challenges that need to be overcome before these promising tools can accomplish significant breakthroughs into the clinical setting.

Description: (1) Background: The athlete’s heart may develop permanent vessel enlargement. The purpose of our study was to define normal values for coronary artery dimensions of endurance athletes by coronary computed tomography angiography (CTA). (2) Methods: Ninety-eight individuals (56.2 ± 11 years) were included into this retrospective matched case-controlled-study. Endurance athletes had regular training volumes of ≥1 h per unit, ≥3–7 times per week (either cycling, running or mountain-endurance). Athletes were matched for age and gender with sedentary controls using propensity score. Quantitative CTA analysis included coronary vessel dimensions (two diameters and area) of the LM, LAD, CX and RCA for all AHA-16-segments. (3) Results: Proximal LAD area and diameter (p = 0.019); proximal/mid CX (diameter and area; p = 0.026 and p = 0.018/p = 0.008 and p = 0.009); mid RCA diameter and area; and proximal RCA diameter were significantly larger in endurance athletes (p 〈 0.05). The left main area (p = 0.708) and diameter (p = 0.809) as well as the mid LAD and distal segments were not different. We present the histograms and data for normal values ±1 and ± 2 SD. (4) Conclusions: Endurance athletes have larger proximal LAD, proximal/mid CX and RCA vessel dimensions, while LM and distal segments are similar. Hence, dilated coronary arteries in endurance athletes (“Athlete’s arteries”) have to be distinguished from diffuse ectatic segments developing during Kawasaki disease or multisystemic inflammation syndrome after COVID-19.

Description: Platelets are functionally versatile blood cells involved in thrombosis, hemostasis, atherosclerosis, and immune response. Platelet interaction with the immediate microenvironment in blood, vasculature, and tissues alters platelet morphology. The quantification of platelet morphodynamics by geometrical parameters (morphometry) can provide important insights into how platelets sense and respond to stimulatory cues in their vicinity. However, the extraction of platelet shapes from phase contrast microscopy images by conventional image processing is difficult. Here, we used a convolutional neural network (CNN) to develop a deep-learning-based approach for the unbiased extraction of information on platelet morphodynamics by phase contrast microscopy. We then investigated the effect of normal and oxidized low-density lipoproteins (LDL, oxLDL) on platelet morphodynamics, spreading, and haptotactic migration. Exposure of platelets to oxLDL led to a decreased spreading area and rate on fibrinogen, accompanied by increased formation of filopodia and impaired formation of lamellipodia. Haptotactic platelet migration was affected by both LDL and oxLDL in terms of decreased migration velocity and reduced directional persistence. Our results demonstrate the use of deep learning in investigating platelet morphodynamics and reveal differential effects of LDL and oxLDL on platelet morphology and platelet–matrix interaction.

Description: Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract. IBD includes Crohn’s disease (CD) and ulcerative colitis (UC). CD can occur in any part of the gastrointestinal tract, whereas UC mainly occurs in the colon and rectum. We previously demonstrated that a novel exopolysaccharide (EPS) produced by a plant-derived bacterium, Lactobacillus paracasei IJH-SONE68, prevents and improves the inflammation in contact dermatitis model mice via oral administration. To evaluate the preventive effect of the EPS against other inflammatory diseases, in the present study, we employed dextran sulfate sodium (DSS)-induced UC model mice. The stool consistency, hematochezia, and colonic atrophy of the mice were improved by the orally administered EPS. We also evaluated the cytokine transcription. Overexpression of the mouse macrophage inflammatory protein 2 mRNA in the colon as a functional homolog of human interleukin-8 was decreased by the orally administered EPS. However, the expression of interleukin-10, which is known as an anti-inflammatory cytokine, was stimulated in the EPS-administrated group. Based on these results, we conclude that the IJH-SONE68-derived EPS is a promising lead material for the development of drugs useful in treating inflammatory diseases such as UC.

Description: Semiaquatic bugs (Hemiptera: Heteroptera: Gerromorpha) are mostly wing-polymorphic species with flight dispersal as an important life history trait, but the specific flight ability and dispersal pattern remain unexplored in most species. This report presents the results of a long-term survey based on the individual marking of more than 23,000 specimens of eight water striders (Gerridae) and a water cricket Velia caprai (Veliidae). Three distinct lentic habitats were sampled (solitary fishponds, systems of nearby fishponds and systems of small, often temporary pools) and one lotic habitat—a small forest stream. Recaptures revealed that three gerrid species tend to stay at the breeding site, but can differ in dispersal via the water surface. Reproductive flightless females disperse most actively via the water surface, possibly bypassing the trade-off between dispersal and reproduction. One species has a sex-dependent dispersal pattern, with females being rather philopatric, whereas males often disperse. Three other gerrid species are highly dispersive and tend to change breeding site. V. caprai, the only lotic species included in this survey, tend to move upstream and possibly compensate for the downstream drift.

Description: Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.

Description: The concept of Heider balance, usually applied to interpersonal relations, is generalized here to opinions gathered in surveys. At first, we compare four algorithms, which drive a matrix dataset to a balanced state. The criterion is that the final state obtained with an algorithm should be as close as possible to the initial state. The result is that deterministic differential equations work better than their Monte Carlo counterparts. Next, we apply the winning algorithms to the matrix of correlations between opinions gathered in American states between 1974 and 1998. The results are interpreted in terms of the classic comfort hypothesis (E. Babbie, 2007).

Description: Self-management support and lifestyle interventions with an empowerment approach have been found to be effective strategies for health improvement among people at risk for or living with type 2 diabetes. Telephone coaching seems particularly efficient for individuals with low socioeconomic status and culturally and linguistically diverse backgrounds. In this mixed methods study, we investigate a telephone-delivered health coaching intervention provided by the diabetes project SMART2D (Self-Management Approach and Reciprocal learning for Type 2 Diabetes) implemented in socioeconomically disadvantaged areas in Stockholm, Sweden. We focus on the interaction between participants and facilitators as part of intervention fidelity. Recorded coaching sessions were scored using an interaction tool and analyzed by exploratory factor analysis and recorded supervisory discussions with facilitators analyzed using thematic analysis. The quantitative analysis showed that the intervention components were delivered as intended; however, differences between facilitators were found. The qualitative data highlighted differences between facilitators in the delivery, especially in relation to dietary and physical activity goalsetting. The level of language skills hindered the delivery flow and the tailoring of sessions to participants’ needs led to different delivery styles. The interaction between facilitators and participants is an important aspect of intervention implementation. Tailoring of interventions is necessary, and language-skilled facilitators are needed to minimize barriers in intervention delivery.

Description: This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BD), as well as the severity of these disorders. Toward this end, we performed an effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of five connections, which discriminated patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), and the frontoparietal and dorsal attention network (middle frontal gyrus (MFG), corresponding to the dorsolateral prefrontal cortex, and frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, four out of the five connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

Description: The monitoring of herpesvirus infection provides useful information when assessing marine mammals’ health. This paper shows the prevalence of herpesvirus infection (80.85%) in 47 cetaceans stranded on the coast of the Valencian Community, Spain. Of the 966 tissues evaluated, 121 tested positive when employing nested-PCR (12.53%). The largest proportion of herpesvirus-positive tissue samples was in the reproductive system, nervous system, and tegument. Herpesvirus was more prevalent in females, juveniles, and calves. More than half the DNA PCR positive tissues contained herpesvirus RNA, indicating the presence of actively replicating virus. This RNA was most frequently found in neonates. Fourteen unique sequences were identified. Most amplified sequences belonged to the Gammaherpesvirinae subfamily, but a greater variation was found in Alphaherpesvirinae sequences. This is the first report of systematic herpesvirus DNA and RNA determination in free-ranging cetaceans. Nine (19.14%) were infected with cetacean morbillivirus and all of them (100%) were coinfected with herpesvirus. Lesions similar to those caused by herpesvirus in other species were observed, mainly in the skin, upper digestive tract, genitalia, and central nervous system. Other lesions were also attributable to concomitant etiologies or were nonspecific. It is necessary to investigate the possible role of herpesvirus infection in those cases.

Description: A case study involving a healthy trained male athlete who completed a 786 km multi-stage ultra-trail race. Several markers were analyzed in blood and urine samples: creatinine (SCR) for kidney damage, sodium ([Na+]) for hyponatremia, creatine kinase (CK) for exertional rhabdomyolysis, as well as other hematological values. Samples were taken before and after the race and during the recovery period (days 2 and 9 after the race). Results showed: SCR = 1.13 mg/dL, [Na+] =139 mmol/L and CK = 1.099 UI/L. Criteria for the determination of acute kidney damage were not met, and [Na+] concentration was above 135 mEq/L, indicating the absence of hyponatremia. Exertional rhabdomyolysis was suffered by the athlete (baseline CK increased fivefold), though this situation was reverted after 9 days of recovery. Ultra-trail races cause biochemical changes in athletes, which should be known about by healthcare professionals.

Description: There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of FES. However, the protein–protein interaction (PPI) network of FEP/FES is not established. The aim of the current study was to delineate a) the characteristics of the PPI network of AN-FEP and its transition to FES; and b) the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. Toward this end, we used PPI network, enrichment, and annotation analyses. FEP and FEP/FES are strongly associated with a response to a bacterium, alterations in Toll-Like Receptor-4 and nuclear factor-κB signaling, and the Janus kinases/signal transducer and activator of the transcription proteins pathway. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation, and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation, in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin and Wnt/catenin signaling, and adherens junction organization. Multiple interactions between reduced brain derived neurotrophic factor, E-cadherin, and β-catenin and disrupted schizophrenia-1 (DISC1) expression increase the vulnerability to the neurotoxic effects of immune molecules, including cytokines and complement factors. In summary: FEP and FES are systemic neuro-immune disorders that are probably triggered by a bacterial stimulus which induces neuro-immune toxicity cascades that are overexpressed in people with reduced anti-inflammatory and miRNA protections, cell–cell junction organization, and neurotrophin and Wnt/catenin signaling.

Description: Cancer stromal cells play a role in promoting tumor relapse and therapeutic resistance. Therefore, the current treatment paradigms for cancers are usually insufficient to eradicate cancer cells, and anti-cancer therapeutic strategies targeting stromal cells have been developed. Cancer-associated fibroblasts (CAFs) are perpetually activated fibroblasts in the tumor stroma. CAFs are the most abundant and highly heterogeneous stromal cells, and they are critically involved in cancer occurrence and progression. These effects are due to their various roles in the remodeling of the extracellular matrix, maintenance of cancer stemness, modulation of tumor metabolism, and promotion of therapy resistance. Recently, biomaterials and nanomaterials based on CAFs have been increasingly developed to perform gene or protein expression analysis, three-dimensional (3D) co-cultivation, and targeted drug delivery in cancer treatment. In this review, we systematically summarize the current research to fully understand the relevant materials and their functional diversity in CAFs, and we highlight the potential clinical applications of CAFs-oriented biomaterials and nanomaterials in anti-cancer therapy.

Description: Background: There is still no wide agreement regarding the efficacy of the serum levels of C-reactive protein (CRPs), pleural fluid levels of CRP (CRPpf), and their ratio (CRPr) in the discrimination between transudative (Tr) and exudative (Ex) pleural effusions (PEs). Most of the previous studies were conducted on small cohorts, and the role of CRPs in the CRPpf gradient (CRPg) in this discrimination has not been previously reported. The present study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPg, and CRPr in the discrimination between TrPE and ExPE in a relatively large cohort of patients with PE. Methods: The study population included 492 patients with PE, 210 of them with TrPE and 282 with ExPE. The levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: The mean levels of CRPs, CRPpf, CRPg, and CRPr of the TrPEs were 11.3 ± 5.7 mg/L, 4.6 ± 2.8 mg/L, 6.7 ± 3.9 mg/L, and 0.40 ± 0.14, respectively, and for the ExPEs, they were 140.5 ± 112.8 mg/L, 52.8 ± 53.2 mg/L, 87.2 ± 72.4 mg/L, and 0.37 ± 0.15, respectively. The levels of CRPs, CRPpf, and CRPg were significantly higher in the ExPEs than in the TrPEs (p 〈 0.0001). No significant difference was found between the two groups for the levels of CRPr (p = 0.15). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating TrPE from ExPE was for CRPs, 20.5 mg/L with area under the curve (AUC) = 97% and p 〈 0.0001; for CRPpf, 9.9 mg/L with AUC = 95% and p 〈 0.0001; and for CRPg, 13.6 mg/L with AUC = 96% and p 〈 0.0001. Conclusion: CRPs, CRPpf, and CRPg are strong markers for discrimination between TrPE and ExPE, while CRPr has no role in this discrimination.

Description: Curcumin, a bioactive polyphenol, is known to have anticancer properties. In this study, the effectiveness of curcumin pretreatment as a strategy for radio-sensitizing glioblastoma cell lines was explored. For this, U87 and T98 cells were treated with curcumin, exposed to 2 Gy or 4 Gy of irradiation, and the combined effect was compared to the antiproliferative effect of each agent when given individually. Cell viability and proliferation were evaluated with the trypan blue exclusion assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic effects of the combination treatment were analyzed with CompuSyn software. To examine how the co-treatment affected different phases of cell-cycle progression, a cell-cycle analysis via flow cytometry was performed. Treatment with curcumin and radiation significantly reduced cell viability in both U87 and T98 cell lines. The combination treatment arrested both cell lines at the G2/M phase to a higher extent than radiation or curcumin treatment alone. The synergistic effect of curcumin when combined with temozolomide resulted in increased tumor cell death. Our results demonstrate for the first time that low doses of curcumin and irradiation exhibit a strong synergistic anti-proliferative effect on glioblastoma cells in vitro. Therefore, this combination may represent an innovative and promising strategy for the treatment of glioblastoma, and further studies are needed to fully understand the molecular mechanism underlying this effect.

Description: Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut–brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson’s disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

Description: Birds use song for several goals as defending territory, alerting a partner to the presence of a predator, or wooing a female for breeding. This study aims to identify the morphometric parameters which determine the variability of the number of syllables in the “sexy” songs of yellow-fronted canary. For this purpose, sixteen morphometric parameters were measured among 170 yellow-fronted canaries captured, in four agroecological zones in North Benin. The results showed that the morphometry of yellow-fronted canary varies according to its habitat and the type of song. The categorization of the sample studied allowed to retain two groups which differ in the importance of body characters and the number of sexy syllables issued when singing. Yellow-fronted canaries from the Sudanese climate zone not only have superior morphometric characters compared to other zones, but also have a song composed of several different sexy syllables. A binary logistic regression model with selection of variables revealed that the index of beak shape, abdomen length, and tail length are the determining characteristics of the number of sexy syllables. These results are needed for future breeding and conservation studies of the species.

Description: Inhaled nebulized interferon (IFN)-α and IFN-β have been shown to be effective in the management of coronavirus disease 2019 (COVID-19). We aimed to construct a virus-free rapid detection system for high-throughput screening of IFN-like compounds that induce viral RNA degradation and suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We prepared a SARS-CoV-2 subreplicon RNA expression vector which contained the SARS-CoV-2 5′-UTR, the partial sequence of ORF1a, luciferase, nucleocapsid, ORF10, and 3′-UTR under the control of the cytomegalovirus promoter. The expression vector was transfected into Calu-3 cells and treated with IFN-α and the IFNAR2 agonist CDM-3008 (RO8191) for 3 days. SARS-CoV-2 subreplicon RNA degradation was subsequently evaluated based on luciferase levels. IFN-α and CDM-3008 suppressed SARS-CoV-2 subreplicon RNA in a dose-dependent manner, with IC50 values of 193 IU/mL and 2.54 μM, respectively. HeLa cells stably expressing SARS-CoV-2 subreplicon RNA were prepared and treated with the IFN-α and pan-JAK inhibitor Pyridone 6 or siRNA-targeting ISG20. IFN-α activity was canceled with Pyridone 6. The knockdown of ISG20 partially canceled IFN-α activity. Collectively, we constructed a virus-free rapid detection system to measure SARS-CoV-2 RNA suppression. Our data suggest that the SARS-CoV-2 subreplicon RNA was degraded by IFN-α-induced ISG20 exonuclease activity.

Description: Over the last few years, there has been a growing interest in the study of lightweight composite materials. Due to their tailorable properties and unique characteristics (high strength, flexibility and stiffness), glass (GFs) and carbon (CFs) fibers are widely used in the production of advanced polymer matrix composites. Glass Fiber-Reinforced Polymer (GFRP) and Carbon Fiber-Reinforced Polymer (CFRP) composites have been developed by different fabrication methods and are extensively used for diverse engineering applications. A considerable amount of research papers have been published on GFRP and CFRP composites, but most of them focused on particular aspects. Therefore, in this review paper, a detailed classification of the existing types of GFs and CFs, highlighting their basic properties, is presented. Further, the oldest to the newest manufacturing techniques of GFRP and CFRP composites have been collected and described in detail. Furthermore, advantages, limitations and future trends of manufacturing methodologies are emphasized. The main properties (mechanical, vibrational, environmental, tribological and thermal) of GFRP and CFRP composites were summarized and documented with results from the literature. Finally, applications and future research directions of FRP composites are addressed. The database presented herein enables a comprehensive understanding of the GFRP and CFRP composites’ behavior and it can serve as a basis for developing models for predicting their behavior.

Description: With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, ethnicity/race, and socioeconomic position from PubMed’s inception to May 2021. Ultimately, 20 articles were included in the review, most (75%) of them carried out in the United States. Males were found to have a higher NAFLD prevalence (three articles), while available evidence suggests that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood of progression and complications (five articles). In conclusion, globally there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social group. Further research on this issue is warranted.

Description: Cadmium (Cd2+) pollution occurring in salt-affected soils has become an increasing environmental concern in the world. Fast-growing poplars have been widely utilized for phytoremediation of soil contaminating heavy metals (HMs). However, the woody Cd2+-hyperaccumulator, Populus × canescens, is relatively salt-sensitive and therefore cannot be directly used to remediate HMs from salt-affected soils. The aim of the present study was to testify whether colonization of P. × canescens with ectomycorrhizal (EM) fungi, a strategy known to enhance salt tolerance, provides an opportunity for affordable remediation of Cd2+-polluted saline soils. Ectomycorrhization with Paxillus involutus strains facilitated Cd2+ enrichment in P. × canescens upon CdCl2 exposures (50 μM, 30 min to 24 h). The fungus-stimulated Cd2+ in roots was significantly restricted by inhibitors of plasmalemma H+-ATPases and Ca2+-permeable channels (CaPCs), but stimulated by an activator of plasmalemma H+-ATPases. NaCl (100 mM) lowered the transient and steady-state Cd2+ influx in roots and fungal mycelia. Noteworthy, P. involutus colonization partly reverted the salt suppression of Cd2+ uptake in poplar roots. EM fungus colonization upregulated transcription of plasmalemma H+-ATPases (PcHA4, 8, 11) and annexins (PcANN1, 2, 4), which might mediate Cd2+ conductance through CaPCs. EM roots retained relatively highly expressed PcHAs and PcANNs, thus facilitating Cd2+ enrichment under co-occurring stress of cadmium and salinity. We conclude that ectomycorrhization of woody hyperaccumulator species such as poplar could improve phytoremediation of Cd2+ in salt-affected areas.

Description: Acute respiratory inflammation, most commonly resulting from bacterial or viral infection, is one of the leading causes of death and disability worldwide. The inflammatory lipid mediator prostaglandin D2 (PGD2) and its rate-limiting enzyme, hematopoietic PGD synthase (hPGDS), are well-known drivers of allergic pulmonary inflammation. Here, we sought to investigate the source and role of hPGDS-derived PGD2 in acute pulmonary inflammation. Murine bronchoalveolar monocytes/macrophages from LPS- but not OVA-induced lung inflammation released significant amounts of PGD2. Accordingly, human monocyte-derived macrophages expressed high basal levels of hPGDS and released significant levels of PGD2 after LPS/IFN-γ, but not IL-4 stimulation. Human peripheral blood monocytes secreted significantly more PGD2 than monocyte-derived macrophages. Using human precision-cut lung slices (PCLS), we observed that LPS/IFN-γ but not IL-4/IL-13 drive PGD2 production in the lung. HPGDS inhibition prevented LPS-induced PGD2 release by human monocyte-derived macrophages and PCLS. As a result of hPGDS inhibition, less TNF-α, IL-6 and IL-10 could be determined in PCLS-conditioned medium. Collectively, this dataset reflects the time-dependent release of PGD2 by human phagocytes, highlights the importance of monocytes and macrophages as PGD2 sources and suggests that hPGDS inhibition might be a potential therapeutic option for acute, non-allergic lung inflammation.

Description: Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty-two trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (−0.36 (−0.71 to −0.01)), glycated hemoglobulin (HbA1c) (−0.74 (−1.13 to −0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (−0.58 (−1.13 to −0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (−0.27 (−0.37 to −0.18)), total cholesterol (−0.60 (−0.88 to −0.32)), low density lipoprotein (LDL) (−0.54 (−0.85 to −0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker’s tumor necrosis factor-alpha (TNF-α) (−0.13 (−0.75 to 0.48)) and c-reactive protein (CRP) (−0.72 (−1.70 to 0.27)), as well as weight (−0.09 (−0.24 to 0.07)) and BMI (−0.13 (−0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000–2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration.

Description: Electrochemical devices, especially energy storage, have been around for many decades. Liquid electrolytes (LEs), which are known for their volatility and flammability, are mostly used in the fabrication of the devices. Dye-sensitized solar cells (DSSCs) and quantum dot sensitized solar cells (QDSSCs) are also using electrochemical reaction to operate. Following the demand for green and safer energy sources to replace fossil energy, this has raised the research interest in solid-state electrochemical devices. Solid polymer electrolytes (SPEs) are among the candidates to replace the LEs. Hence, understanding the mechanism of ions’ transport in SPEs is crucial to achieve similar, if not better, performance to that of LEs. In this paper, the development of SPE from basic construction to electrolyte optimization, which includes polymer blending and adding various types of additives, such as plasticizers and fillers, is discussed.

Description: Cutaneous metastases (CMs) account for 2% of all skin malignancies, and nearly 70% of CMs in women originate from breast cancer (BC). CMs are usually associated with poor prognosis, are difficult to treat, and can pose diagnostic problems, such as in histopathological diagnosis when occurring long after development of the primary tumor. In addition, the molecular differences between the primary tumors and their CMs, and between CMs and metastases in other organs, are not well defined. Here, we review the main clinical, pathological, and molecular characteristics of breast cancer CMs. Identifying molecular markers in primary BC that predict CM and can be used to determine the molecular differences between primary tumors and their metastases is of great interest for the design of new therapeutic approaches.

Description: Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor- abiraterone and androgen receptor antagonists- enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

Description: This research concerns a design and construction of a bone mineral density (BMD) and bone mineral content (BMC) measurement system based on dual energy x-ray absorptiometry (DEXA). An indirect x-ray detector is designed by optical coupling CMOS sensor with image on the intensifying screen. A dedicated microcontroller x-ray apparatus is used as an x-ray source to capture two energy level x-ray of middle phalanges bone of middle finger. The captured image is processed based on modified Beer-Lambert law to compute bone mineral density. Bone mineral content is also computed by determining the area of the phalanges bone using active contour. The designed bone mineral density (BMD) and bone mineral content (BMC) measurement system is low-cost and hence can be distributed at district hospital for screening purposes of Osteoporosis of the elderly. Compared with BMD measured from commercial model, BMD measurement of our system acquires linear relation with R2 equals 0.969. The mean square error between the normalized BMD value and that of the commercial model is 0.0000981.

Description: Falls are a major cause of morbidity and mortality in neurological disorders. Technical means of detecting falls are of high interest as they enable rapid notification of caregivers and emergency services. Such approaches must reliably differentiate between normal daily activities and fall events. A promising technique might be based on the classification of movements based on accelerometer signals by machine-learning algorithms, but the generalizability of classifiers trained on laboratory data to real-world datasets is a common issue. Here, three machine-learning algorithms including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), and Random Forest (RF) were trained to detect fall events. We used a dataset containing intentional falls (SisFall) to train the classifier and validated the approach on a different dataset which included real-world accidental fall events of elderly people (FARSEEING). The results suggested that the linear SVM was the most suitable classifier in this cross-dataset validation approach and reliably distinguished a fall event from normal everyday activity at an accuracy of 93% and similarly high sensitivity and specificity. Thus, classifiers based on linear SVM might be useful for automatic fall detection in real-world applications.

Description: Small-compound databases contain a large amount of information for metabolites and metabolic pathways. However, the plethora of such databases and the redundancy of their information lead to major issues with analysis and standardization. A lack of preventive establishment of means of data access at the infant stages of a project might lead to mislabelled compounds, reduced statistical power, and large delays in delivery of results. We developed MetaFetcheR, an open-source R package that links metabolite data from several small-compound databases, resolves inconsistencies, and covers a variety of use-cases of data fetching. We showed that the performance of MetaFetcheR was superior to existing approaches and databases by benchmarking the performance of the algorithm in three independent case studies based on two published datasets.

Description: Background. Left ventricular mechanical dyssynchrony (LVMD), left ventricular hypertrophy, and impaired cardiac sympathetic innervation are closely related to the development of heart failure (HF) and unfavorable outcomes. Methods and Results. A total of 705 consecutive HF patients with reduced left ventricular ejection fraction (EF) 〈 50% were registered in our hospital HF database. LVMD and left ventricular mass index (LVMI) were evaluated three-dimensionally by gated myocardial perfusion SPECT. LVMD was measured as a heterogeneity index (phase SD) of the regional contraction phase angles calculated by Fourier analysis. Cardiac sympathetic innervation was quantified as a normalized heart-to-mediastinum ratio (HMR) of the 123I-metaiodobenzylguanidine (MIBG) activity. The patients were followed up with a primary end point of lethal cardiac events (CEs) for 42 months. CEs were documented in 246 of the HF patients who had a greater phase SD, greater LVMI, and lower MIBG HMR than those in HF patients without CEs. In the overall multivariate analysis, phase SD, LVMI, and MIBG HMR were identified as significant CE determinants. The three biomarkers were incrementally related to increases in CE risks. Conclusions. Assessment of cardiac sympathetic innervation can further stratify patients with systolic heart failure at increased cardiac risk identified by left ventricular hypertrophy and mechanical dyssynchrony.

Description: Objective: To analyze the temporal trend and spatial patterns of schistosomiasis-related morbidity in Northeast Brazil, 2001−2017. Methods: Ecological study, of time series and spatial analysis, based on case notifications and hospital admission data, as provided by the Ministry of Health. Results: Of a total of 15,574,392 parasitological stool examinations, 941,961 (6.0%) were positive, mainly on the coastline of Pernambuco, Alagoas and Sergipe states. There was a reduction from 7.4% (2002) to 3.9% (2017) of positive samples and in the temporal trend of the detection rate (APC—11.6*; Confidence Interval 95%—13.9 to −9.1). There was a total of 5879 hospital admissions, with 40.4% in Pernambuco state. The hospitalization rate reduced from 0.82 (2001) to 0.02 (2017) per 100,000 inhabitants. Conclusion: Despite the reduction in case detection and hospitalizations, the persistence of focal areas of the disease in coastal areas is recognized. This reduction may indicate a possible positive impact of control on epidemiological patterns, but also operational issues related to access to healthcare and the development of surveillance and control actions in the Unified Health System.

Description: Objective: To investigate two commercial software and their efficacy in the assessment of chest CT sequelae in patients affected by COVID-19 pneumonia, comparing the consistency of tools. Materials and Methods: Included in the study group were 120 COVID-19 patients (56 women and 104 men; 61 years of median age; range: 21–93 years) who underwent chest CT examinations at discharge between 5 March 2020 and 15 March 2021 and again at a follow-up time (3 months; range 30–237 days). A qualitative assessment by expert radiologists in the infectious disease field (experience of at least 5 years) was performed, and a quantitative evaluation using thoracic VCAR software (GE Healthcare, Chicago, Illinois, United States) and a pneumonia module of ANKE ASG-340 CT workstation (HTS Med & Anke, Naples, Italy) was performed. The qualitative evaluation included the presence of ground glass opacities (GGOs) consolidation, interlobular septal thickening, fibrotic-like changes (reticular pattern and/or honeycombing), bronchiectasis, air bronchogram, bronchial wall thickening, pulmonary nodules surrounded by GGOs, pleural and pericardial effusion, lymphadenopathy, and emphysema. A quantitative evaluation included the measurements of GGOs, consolidations, emphysema, residual healthy parenchyma, and total lung volumes for the right and left lung. A chi-square test and non-parametric test were utilized to verify the differences between groups. Correlation coefficients were used to analyze the correlation and variability among quantitative measurements by different computer tools. A receiver operating characteristic (ROC) analysis was performed. Results: The correlation coefficients showed great variability among the quantitative measurements by different tools when calculated on baseline CT scans and considering all patients. Instead, a good correlation (≥0.6) was obtained for the quantitative GGO, as well as the consolidation volumes obtained by two tools when calculated on baseline CT scans, considering the control group. An excellent correlation (≥0.75) was obtained for the quantitative residual healthy lung parenchyma volume, GGO, consolidation volumes obtained by two tools when calculated on follow-up CT scans, and for residual healthy lung parenchyma and GGO quantification when the percentage change of these volumes were calculated between a baseline and follow-up scan. The highest value of accuracy to identify patients with RT-PCR positive compared to the control group was obtained by a GGO total volume quantification by thoracic VCAR (accuracy = 0.75). Conclusions: Computer aided quantification could be an easy and feasible way to assess chest CT sequelae due to COVID-19 pneumonia; however, a great variability among measurements provided by different tools should be considered.

Description: We determined the association between T. gondii seropositivity and a history of sexual promiscuity. The study included 3933 people (mean age: 41.81 ± 14.31 years) who attended public health facilities. Face-to-face interviews were used to collect data. Enzyme immunoassays were used to determine anti-T. gondii IgG and IgM antibodies. Anti-T. gondii IgG antibodies were found in 57 (18.1%) of 315 individuals with sexual promiscuity and in 374 (10.3%) of 3618 individuals without this practice (OR: 1.91; 95% CI: 1.41–2.60; p 〈 0.0001). High (〉150 IU/mL) levels of anti-T. gondii IgG antibodies were found in 29 (9.2%) of the 315 participants with sexual promiscuity and in 167 (4.6%) of the 3618 participants without this history (OR: 2.09; 95% CI: 1.38–3.16; p = 0.0003). The association of sexual promiscuity with T. gondii seropositivity and serointensity was observed in men but not in women. Sexual promiscuity was associated with T. gondii seropositivity in all age groups studied (≤30 years, 31–50 years, and 〉50 years) and with T. gondii serointensity in two age groups (≤30 years, and 〉50 years). No difference in the frequencies of anti-T. gondii IgM antibodies among the groups was found. Our findings indicate that T. gondii seropositivity and serointensity are associated with sexual promiscuity.

Description: An ubiquinone derivative, pseudoalteromone A (1), has been isolated from two marine-derived Pseudoalteromonas spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.

Description: Targeting the redox balance of malignant cells via the delivery of high oxidative stress unlocks a potential therapeutic strategy against glioblastoma (GBM). We investigated a novel reactive oxygen species (ROS)-inducing combination treatment strategy, by increasing exogenous ROS via cold atmospheric plasma and inhibiting the endogenous protective antioxidant system via auranofin (AF), a thioredoxin reductase 1 (TrxR) inhibitor. The sequential combination treatment of AF and cold atmospheric plasma-treated PBS (pPBS), or AF and direct plasma application, resulted in a synergistic response in 2D and 3D GBM cell cultures, respectively. Differences in the baseline protein levels related to the antioxidant systems explained the cell-line-dependent sensitivity towards the combination treatment. The highest decrease of TrxR activity and GSH levels was observed after combination treatment of AF and pPBS when compared to AF and pPBS monotherapies. This combination also led to the highest accumulation of intracellular ROS. We confirmed a ROS-mediated response to the combination of AF and pPBS, which was able to induce distinct cell death mechanisms. On the one hand, an increase in caspase-3/7 activity, with an increase in the proportion of annexin V positive cells, indicates the induction of apoptosis in the GBM cells. On the other hand, lipid peroxidation and inhibition of cell death through an iron chelator suggest the involvement of ferroptosis in the GBM cell lines. Both cell death mechanisms induced by the combination of AF and pPBS resulted in a significant increase in danger signals (ecto-calreticulin, ATP and HMGB1) and dendritic cell maturation, indicating a potential increase in immunogenicity, although the phagocytotic capacity of dendritic cells was inhibited by AF. In vivo, sequential combination treatment of AF and cold atmospheric plasma both reduced tumor growth kinetics and prolonged survival in GBM-bearing mice. Thus, our study provides a novel therapeutic strategy for GBM to enhance the efficacy of oxidative stress-inducing therapy through a combination of AF and cold atmospheric plasma.

Description: Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

Description: Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.

Description: Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, high abundance and high m/z sphingolipid, and low abundance glycerophospholipid metabolic phenotype across the NSCLC samples. At the class level, high abundances of sterol esters and cardiolipins were observed suggesting altered stearoyl-CoA desaturase 1 (SCD1) or acetyl-CoA acetyltransferase (ACAT1) activity and altered human cardiolipin synthase 1 or lysocardiolipin acyltransferase activity respectively, the latter of which is known to confer apoptotic resistance. The presence of a shared metabolic phenotype across a variety of genetically distinct NSCLC subtypes suggests that this phenotype is necessary for NSCLC development and may result from multiple distinct genetic lesions. Thus, targeting the shared affected pathways may be beneficial for a variety of genetically distinct NSCLC subtypes.

Description: Streptococcus pyogenes is a significant pathogen that causes skin and upper respiratory tract infections and non-suppurative complications, such as acute rheumatic fever and post-strep glomerulonephritis. Multidrug resistance has emerged in S. pyogenes strains, making them more dangerous and pathogenic. Hence, it is necessary to identify and develop therapeutic methods that would present novel approaches to S. pyogenes infections. In the current study, a subtractive proteomics approach was employed to core proteomes of four strains of S. pyogenes using several bioinformatic software tools and servers. The core proteome consists of 1324 proteins, and 302 essential proteins were predicted from them. These essential proteins were analyzed using BLASTp against human proteome, and the number of potential targets was reduced to 145. Based on subcellular localization prediction, 46 proteins with cytoplasmic localization were chosen for metabolic pathway analysis. Only two cytoplasmic proteins, i.e., chromosomal replication initiator protein DnaA and two-component response regulator (TCR), were discovered to have the potential to be novel drug target candidates. Three-dimensional (3D) structure prediction of target proteins was carried out via the Swiss Model server. Molecular docking approach was employed to screen the library of 1000 phytochemicals against the interacting residues of the target proteins through the MOE software. Further, the docking studies were validated by running molecular dynamics simulation and highly popular binding free energy approaches of MM-GBSA and MM-PBSA. The findings revealed a promising candidate as a novel target against S. pyogenes infections.

Description: The impact of plum pox virus (PPV) on sour cherry (Prunus cerasus L.) productivity has been studied by comparing the yield of PPV-infected and PPV-free fruit-bearing trees. A total of 152 16- to 17-year-old trees of nine cultivars and hybrids were surveyed in the production orchards (cultivar collection and hybrid testing plots) in the Republic of Tatarstan, Russia. Sixty trees tested positive for PPV using ELISA and RT-PCR. Among them, 58 PPV isolates belonged to the strain C and the other 2 isolates to the strain CV. For the cultivars Sevastyanovskaya, Shakirovskaya, hybrids 88-2 and 80-8, the average (2012 to 2019) productivity of infected trees was 38% to 45% lower than for PPV-free trees of the same cultivar or hybrid. No ilarviruses (prunus necrotic ringspot virus, prune dwarf virus, apple mosaic virus, American plum line pattern virus) were detected in PPV-infected trees, suggesting that reduced cherry productivity was attributed to the PPV infection. Thus, it was shown for the first time that PPV can reduce the productivity of at least some sour cherry cultivars and hybrids, and strain C isolates are responsible for crop losses.

Description: Trajectory tracking is a key technology for precisely controlling autonomous vehicles. In this paper, we propose a trajectory-tracking method based on model predictive control. Instead of using the forward Euler integration method, the backward Euler integration method is used to establish the predictive model. To meet the real-time requirement, a constraint is imposed on the control law and the warm-start technique is employed. The MPC-based controller is proved to be stable. The simulation results demonstrate that, at the cost of no or a little increase in computational time, the tracking performance of the controller is much better than that of controllers using the forward Euler method. The maximum lateral errors are reduced by 69.09%, 47.89% and 78.66%. The real-time performance of the MPC controller is good. The calculation time is below 0.0203 s, which is shorter than the control period.

Description: Motto: All truth passes through three stages [...]

Description: To determine the relationships between limiting factors and neuromuscular activity during a self-paced 20-km cycling time trial and evaluate the effect of environmental conditions on fatigue indices. Methods: Ten endurance-trained and heat-acclimated athletes performed in three conditions (ambient temperature, relative humidity): HUMID (30 °C, 90%), DRY (35 °C, 46%) and NEUTRAL (22 °C, 55%). Voluntary muscular contractions and electromagnetic stimulations were recorded before and after the time trials to assess fatigue. The data on performance, temperature, heat storage, electromyogram, heart rate and rating of perceived exertion data were analyzed. Results: Performance was impaired in DRY and HUMID compared with NEUTRAL environment (p 〈 0.05). The force developed by the vastus lateral muscle during stimulation of the femoral nerve remained unchanged across conditions. The percentage of integrated electromyogram activity, normalized by the value attained during the pre-trial maximal voluntary contraction, decreased significantly throughout the trial only in HUMID condition (p 〈 0.01). Neuromuscular activity in peripheral skeletal muscle started to fall from the 11th km in HUMID and the 15th km in DRY condition, although core temperature did not reach critical values. Conclusions: These alterations suggest that afferences from core/skin temperature regulate the central neural motor drive, reducing the active muscle recruited during prolonged exercise in the heat in order to prevent the system from hyperthermia.

Description: Stochastic gradient sg-based algorithms for Markov chain Monte Carlo sampling (sgmcmc) tackle large-scale Bayesian modeling problems by operating on mini-batches and injecting noise on sgsteps. The sampling properties of these algorithms are determined by user choices, such as the covariance of the injected noise and the learning rate, and by problem-specific factors, such as assumptions on the loss landscape and the covariance of sg noise. However, current sgmcmc algorithms applied to popular complex models such as Deep Nets cannot simultaneously satisfy the assumptions on loss landscapes and on the behavior of the covariance of the sg noise, while operating with the practical requirement of non-vanishing learning rates. In this work we propose a novel practical method, which makes the sg noise isotropic, using a fixed learning rate that we determine analytically. Extensive experimental validations indicate that our proposal is competitive with the state of the art on sgmcmc.

Description: Parkinson’s disease (PD) is characterized by four pathognomonic hallmarks: (1) motor and non-motor deficits; (2) neuroinflammation and oxidative stress; (3) pathological aggregates of the α-synuclein (α-syn) protein; (4) neurodegeneration of the nigrostriatal system. Recent evidence sustains that the aggregation of pathological α-syn occurs in the early stages of the disease, becoming the first trigger of neuroinflammation and subsequent neurodegeneration. Thus, a therapeutic line aims at striking back α-synucleinopathy and neuroinflammation to impede neurodegeneration. Another therapeutic line is restoring the compromised dopaminergic system using neurotrophic factors, particularly the glial cell-derived neurotrophic factor (GDNF). Preclinical studies with GDNF have provided encouraging results but often lack evaluation of anti-α-syn and anti-inflammatory effects. In contrast, clinical trials have yielded imprecise results and have reported the emergence of severe side effects. Here, we analyze the discrepancy between preclinical and clinical outcomes, review the mechanisms of the aggregation of pathological α-syn, including neuroinflammation, and evaluate the neurorestorative properties of GDNF, emphasizing its anti-α-syn and anti-inflammatory effects in preclinical and clinical trials.

Description: (1) Background: The present study aimed to analyze medication adherence and its effect on blood pressure (BP) control and assess the prevalence of treatment-resistant hypertension (TRH) among newly treated hypertensive patients in the United Arab Emirates (UAE); (2) Methods: A retrospective chart review was conducted to evaluate 5308 naïve hypertensive adults registered for the treatment across Abu Dhabi Health Services (SEHA) clinics in Abu Dhabi in 2017. After collecting data regarding basic details and BP measurements, patients were followed up for six months. Patients who did not reach BP targets despite taking three or more antihypertensive medications were defined as TRH; (3) Results: The overall adherence to antihypertensive treatment was 42%. At 6-month, a significant reduction in BP was observed in patients adherent to medications (systolic: −4.5 mm Hg and diastolic: −5.9 mm Hg) than those who were nonadherent to antihypertensive therapy (1.15 mm Hg and 3.59 mm Hg). Among 189 patients using three or more antihypertensive medications for six months, only 34% (n = 64) were adherent to the treatment, and only 13.7% (n = 26) reached the BP target. The prevalence of TRH was 20.1%; (4) Conclusions: Medication adherence and BP control among the participants were suboptimal. The study shows a high prevalence of TRH among newly treated hypertensives in the UAE. More extraordinary efforts toward improving adherence to antihypertensive therapy and more focus toward BP control and TRH are urgently needed.

Description: Potassium (K) is a crucial element of plant nutrition, involved in many physiological and molecular processes. K+ membrane transporters are playing a pivotal role in K+ transport and tissue distribution as well as in various plant stress responses and developmental processes. Two-pore K+-channels (TPKs) are essential to maintain plant K+ homeostasis and are mainly involved in potassium transport from the vacuoles to the cytosol. Besides vacuolar specialization, some TPK members display different membrane localization including plasma membrane, protein storage vacuole membrane, and probably the organelles. In this manuscript, we elucidate the evolution of the voltage-independent TPK (two-pore K+-channels) family, which could be represented in some species by one pore, K+-inward rectifier (Kir)-like channels. A comprehensive investigation of existing databases and application of modern bioinformatic tools allowed us to make a detailed phylogenetic inventory of TPK/KCO3 (KCO: potassium channel, outward rectifying) channels through many taxa and gain insight into the evolutionary origin of TPK family proteins. Our results reveal the fundamental evolutional difference between the first and second pores, traced throughout multiple taxa variations in the ion selection filter motif, presence of thansposon, and methylation site in the proximity of some KCO members and suggest virus-mediated horizontal transfer of a KCO3-like ancestor by viruses. Additionally, we suggest several interconnected hypotheses to explain the obtained results and provide a theoretical background for future experimental validation.

Description: In the original article [...]

Description: In the last two decades, abnormal Ras (rat sarcoma protein)–ERK (extracellular signal-regulated kinase) signalling in the brain has been involved in a variety of neuropsychiatric disorders, including drug addiction, certain forms of intellectual disability, and autism spectrum disorder. Modulation of membrane-receptor-mediated Ras activation has been proposed as a potential target mechanism to attenuate ERK signalling in the brain. Previously, we showed that a cell penetrating peptide, RB3, was able to inhibit downstream signalling by preventing RasGRF1 (Ras guanine nucleotide-releasing factor 1), a neuronal specific GDP/GTP exchange factor, to bind Ras proteins, both in brain slices and in vivo, with an IC50 value in the micromolar range. The aim of this work was to mutate and improve this peptide through computer-aided techniques to increase its inhibitory activity against RasGRF1. The designed peptides were built based on the RB3 peptide structure corresponding to the α-helix of RasGRF1 responsible for Ras binding. For this purpose, the hydrogen-bond surrogate (HBS) approach was exploited to maintain the helical conformation of the designed peptides. Finally, residue scanning, MD simulations, and MM-GBSA calculations were used to identify 18 most promising α-helix-shaped peptides that will be assayed to check their potential activity against Ras-RasGRF1 and prevent downstream molecular events implicated in brain disorders.

Description: Hirschsprung-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). It has been proposed that gut microbiota, which have an essential role in gut-homeostasis, are associated with HAEC. Recent studies demonstrated an increase in alpha diversity of fecal microbiota over time in HSCR mice and a decrease in diversity after surgery. In addition, clinical studies have reported a reduction in bacterial richness in HSCR children after surgery. Some studies revealed a difference in microbiota between the proximal ganglionic and distal aganglionic intestine and found a difference in bacterial character between fecal and colonic specimens. HAEC studies found an increase in Proteobacteria, especially Escherichia and Enterobacteriaceae, with a decrease in Firmicutes and Bifidobacterium in HAEC patients. However, the direction of alpha diversity in HAEC patients is still controversial. The self-comparison of microbiota in treatment periods suggested that probiotics might improve gut dysbiosis and decrease the frequency of enterocolitis, but some reported contradictory findings. This review comprehensively summarizes and discusses key findings from animal and clinical data of the distinct microbiome associated with HCSR and the association of gut dysbiosis with the development of HAEC. This information should be useful in the establishment of novel interventions to improve gut dysbiosis and prevent enterocolitis in HSCR patients.

Description: Pozol is a Mexican beverage prepared from fermented nixtamalized maize dough. To contribute to understanding its complex microbial ecology, the effect of inoculating on MRS-starch pure and mixed cultures of amylolytic Sii-25124 and non-amylolytic W. confusa 17, isolated from pozol, were studied on their interactions and fermentation parameters. These were compared with L. plantarum A6, an amylolytic strain isolated from cassava. Microbial growth, kinetic parameters, amylolytic activity, lactic acid production, and hydrolysis products from starch fermentation were measured. The population dynamics were followed by qPCR. L. plantarum A6 showed higher enzymatic activity, lactic acid, biomass production, and kinetic parameters than pozol LAB in pure cultures. Mixed culture of each pozol LAB with L. plantarum A6 showed a significant decrease in amylolytic activity, lactic acid yield, specific growth rate, and specific rate of amylase production. The interaction between Sii-25124 and W. confusa 17 increased the global maximum specific growth rate (µ), the lactic acid yield from starch (Ylac/s), lactic acid yield from biomass (Ylac/x), and specific rate of lactic acid production (qlac) by 15, 30, 30, and 40%, respectively, compared with the pure culture of Sii-25124. Interactions between the two strains are essential for this fermentation.

Description: In nature, protists directly participate in litter decomposition and indirectly affect litter decomposition processes by means of their influence on litter microbial communities. To date, relevant studies on litter microbial communities have primarily focused on bacteria and fungi, while relatively little attention has been paid to the characteristics of protozoan communities within damaged ecosystems. Two dominant grass species (Bothriochloa ischaemum and Imperata cylindrica) were selected from China’s “Eighteenth” River tailings dam to explore protozoan community composition and diversity in a degraded mining area and to clarify the influence among key ecological factors and protozoan community characteristics in litter. High-throughput sequencing was used to analyze protozoan community composition and diversity, while correlation analysis was used to explore the relationships between protozoan communities and litter nutrient characteristics, including associative enzyme degradation. Although protozoan communities in litter shared a dominant group at an order level (Colpodida), they differed at a genus level (i.e., Hausmanniella and Tychosporium). Moreover, although the order Cryomonadida positively correlated to total nitrogen (TN) and sucrose, it exhibited an extreme negative correlation to total carbon (TC) and cellulase. Colpodida and Oomycota_X significantly and negatively correlated to litter urease activity. Nutrient characteristics of grass litter in copper tailing dams are important ecological factors that affect protozoan community characteristics. Notable differences were observed among protozoan communities of these two grass species, while litter enzyme activities were closely correlated to protozoan community diversity. The results suggested that Colpodida may play important roles in litter decomposition and nutrient cycling in mining areas.

Description: We recently reported that the inability of osteoarthritic (OA) chondrocytes to repair oxidative stress (OS) induced DNA damage is linked to Cav-1 overexpression/improper localization. We speculated that the senescent status of OA cells was responsible for this Cav-1 dysregulation. Here, to further investigate this hypothesis, we used Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) and investigated Cav-1 function as cells reached replicative senescence or upon stress induced senescence (SIPS). We showed that Cav-1 is upregulated, phosphorylated and translocated to the nucleus in young WJ-MSCs upon acute exogenous OS, and that it returns back to basal/nonphosphorylated levels and exports the nucleus in the recovery phase. However, as cells reach senescence, this regulation is lost. OS did not induce any Cav-1-mediated response, which is concomitant with the inability of older cells to restore DNA damage. Furthermore, downregulation of Cav-1 resulted in persistent OS-induced DNA damage and subsequent onset of senescence. We also report that the establishment of senescence is mediated by autophagy stimulation, since downregulation of autophagy key molecule Atg5, simultaneously with Cav-1 downregulation, was found to inhibit SIPS. Basically, we propose that Cav-1 involvement in DNA damage response can lead to senescence, either because the damage is extensive or because Cav-1 is absent/unable to perform its homeostatic role.

Description: Mitochondria associated membranes (MAMs), as the name suggests, are the membranes that physically and biochemically connect mitochondria with endoplasmic reticulum. MAMs not only structurally but also functionally connect these two important organelles within the cell which were previously thought to exist independently. There are multiple points of communication between ER–mitochondria and MAMs play an important role in both ER and mitochondria functions such as Ca2+ homeostasis, proteostasis, mitochondrial bioenergetics, movement, and mitophagy. The number of disease-related proteins and genes being associated with MAMs has been continually on the rise since its discovery. There is an overwhelming overlap between the biochemical functions of MAMs and processes affected in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Thus, MAMs have received well-deserving and much delayed attention as modulators for ER–mitochondria communication and function. This review briefly discusses the recent progress made in this now fast developing field full of promise for very exciting future therapeutic discoveries.

Description: Ischemic stroke is one of the leading causes of death among the aged population in the world. Experimental stroke models with rodents play a fundamental role in the investigation of the mechanism and impairment of cerebral ischemia. For its celerity and veracity, the 2,3,5-triphenyltetrazolium chloride (TTC) staining of rat brains has been extensively adopted to visualize the infarction, which is subsequently photographed for further processing. Two important tasks are to segment the brain regions and to compute the midline that separates the brain. This paper investigates automatic brain extraction and hemisphere segmentation algorithms in camera-based TTC-stained rat images. For rat brain extraction, a saliency region detection scheme on a superpixel image is exploited to extract the brain regions from the raw complicated image. Subsequently, the initial brain slices are refined using a parametric deformable model associated with color image transformation. For rat hemisphere segmentation, open curve evolution guided by the gradient vector flow in a medial subimage is developed to compute the midline. A wide variety of TTC-stained rat brain images captured by a smartphone were produced and utilized to evaluate the proposed segmentation frameworks. Experimental results on the segmentation of rat brains and cerebral hemispheres indicated that the developed schemes achieved high accuracy with average Dice scores of 92.33% and 97.15%, respectively. The established segmentation algorithms are believed to be potential and beneficial to facilitate experimental stroke study with TTC-stained rat brain images.

Description: Breastfeeding rates remain extremely low in Greece and women with gestational diabetes mellitus and hypothyroidism may experience additional difficulties. The aim of the study was to investigate the effect of a structured individualized lactation educational intervention by a midwife on increasing breastfeeding rates in women with endocrine disorders and low-risk women compared to women receiving standard care, 24 months after delivery. Two-hundred women made up the study population. Half of them were experiencing endocrine pregnancy disorders and 100 women constituted the low-risk pregnancy standard care control group. Women who were breastfeeding exclusively were significantly higher in the midwifery intervention group with endocrine disorders, namely breastfeeding continued at four months (breastfeeding: 20% vs. 12%, exclusive breastfeeding: 50% vs. 26%, p = 0.0228), and at six months after childbirth (breastfeeding: 54% vs. 28%, exclusive breastfeeding: 32% vs. 12%, p = 0.0011), compared to the standard care control group with endocrine disorder. The low-risk midwifery intervention group breastfed at four months (22% vs. 14%, p = 0.0428) and at six months (52% vs. 26%, p = 0.0018) at higher rates compared to the standard care control group. In addition, exclusive breastfeeding was significantly higher in the low-risk midwifery intervention group at four months (46% vs. 20%, p = 0.0102) and six months (38% vs. 4%, p 〈 0.0001) compared to the standard care control group. This study was the first attempt of a structured midwifery breastfeeding education in Greece and its major contribution reflects a significant positive impact on breastfeeding rates in terms of duration and exclusivity in women with gestational endocrine disorders as well as in low-risk women, and could possibly be applied and instituted in everyday clinical practice to increase the low breastfeeding rates in Greece.

Description: Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2%–10% of women experience this condition during reproductive age, 35%–50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis.

Description: The signal-to-noise ratios (SNR) of ultrasonic imaging and non-destructive evaluation (NDE) applications can be greatly improved by driving each piezoelectric transducer (single or in array) with tuned HV capacitive-discharge drivers. These can deliver spikes with kW pulsed power at PRF ≈ 5000 spikes/s, achieving levels higher even than in CW high-power ultrasound: up to 5 kWpp. These conclusions are reached here by applying a new strategy proposed for the accurate modeling of own-design re-configurable HV capacitive drivers. To obtain such rigorous spike modeling, the real effects of very high levels of pulsed intensities (3–10 A) and voltages (300–700 V) were computed. Unexpected phenomena were found: intense brief pulses of driving power and probe emitted force, as well as nonlinearities in semiconductors, though their catalog data include only linear ranges. Fortunately, our piezoelectric and circuital devices working in such an intense regime have not shown serious heating problems, since the finally consumed “average” power is rather small. Intensity, power, and voltage, driving wideband transducers from our capacitive drivers, are researched here in order to drastically improve (∆ 〉〉 40 dB) their ultrasonic “net dynamic range available” (NDRA), achieving emitted forces 〉 240 Newtonspp and receiving ultrasonic signals of up to 76–205 Vpp. These measurements of ultrasonic pulsed voltages, received in NDE and Imaging, are approximately 10,000 larger than those usual today. Thus, NDRA ranges were optimized for three laboratory capacitive drivers (with six commercial transducers), which were successfully applied in the aircraft industry for imaging landing flaps in Boeing wings, despite suffering acoustic losses 〉 120 dB.

Description: Corosolic acid (CA), a bioactive compound obtained from Actinidia chinensis, has potential anti-cancer activities. Glioblastoma (GBM) is a malignant brain tumor and whether CA exerts anti-cancer activity on GBM remains unclear. This study was aimed to explore the anticancer activity and its underlying mechanism of CA in GBM cells. Our findings showed that CA ≤ 20 μM did not affect cell viability and cell proliferative rate of normal astrocyte and four GBM cells. Notably, 10 or 20 μM CA significantly inhibited cell migration and invasion of three GBM cells, decreased the protein level of F-actin and disrupted F-actin polymerization in these GBM cells. Further investigation revealed that CA decreased AXL level by promoting ubiquitin-mediated proteasome degradation and upregulating the carboxyl terminus of Hsc70-interacting protein (CHIP), an inducer of AXL polyubiquitination. CHIP knock-down restored the CA-reduced AXL and invasiveness of GBM cells. Additionally, we observed that CA-reduced Growth arrest-specific protein 6 (GAS6) and inhibited JAK2/MEK/ERK activation, and GAS6 pre-treatment restored attenuated JAK2/MEK/ERK activation and invasiveness of GBM cells. Furthermore, molecular docking analysis revealed that CA might bind to GAS6 and AXL. These findings collectively indicate that CA attenuates the invasiveness of GBM cells, attributing to CHIP upregulation and binding to GAS6 and AXL and subsequently promoting AXL degradation and downregulating GAS6-mediated JAK2/MEK/ERK cascade. Conclusively, this suggests that CA has potential anti-metastatic activity on GBM cells by targeting the CHIP/GAS6/AXL axis.

Description: The aim of this study was to analyze the use of the diagnostic B-scan ultrasound. Should it be made accessible to all surgical centers in Sub-Saharan Africa in order to (i) avoid unnecessary cataract surgery and (ii) evaluate extraocular pathology? This study was conducted in Kinshasa from 2006 to 2019. Three hundred and twenty-three patients were included and separated into two groups. Group 1 included 262 patients with dense cataract. Group 2 consisted of 61 patients with pathologies of the ocular adnexa, and all were examined with a B-scan ultrasound. In group 1, there were 437 systematically screened eyes. Three hundred and ninety-eight eyes (91.08%) showed no abnormalities, 13 (2.97%) retinal detachments were identified, and 15 (3.43%) demonstrated a detached posterior hyaloid membrane. In the second group, 61 patients were examined (group 2). In 20 of them, surgery was performed for biopsy, tumor excision, mucoceles drainage, and palliative treatment. The need for routine B-scan examinations in dense cataract patients seems to be limited and can most likely be replaced by a thorough application of locally available examination techniques. B-scan application is recommended to manage orbital patients in the most cost-effective way.

Description: The objective of this pioneering study was to assess potentially neuroprotective properties of topiramate (TPM), a broad spectrum and newer-generation antiepileptic used against damage to synaptic endings of the temporal lobe neocortex in experimental hyperthermia-induced seizures (HS). TPM (80 mg/kg b.m.) was administered in young male Wistar rats with an intragastric tube before and immediately after HS. Specimens (1 mm3) collected from the neocortex, fixed via transcardial perfusion with paraformaldehyde and glutaraldehyde solution, were routinely processed for transmission-electron microscopic study, i.e., for descriptive and morphometric analysis. The ultrastructure of neocortical neuropil components affected by hyperthermic stress showed distinct swelling of pre and post-synaptic axodendritic and axospinal endings, including total disintegration. Mitochondria were markedly damaged in synaptic structures. Axoplasm of presynaptic boutons contained a decreased number of synaptic vesicles. Synaptic junctions showed active zone-shortening. Preventive administration of TPM before HS induction demonstrated neuroprotective effects against synaptic damage in approximately 1/4 of these structures. Interestingly, beneficial effects on synapsis morphology were more common in perivascular zones close to well-preserved capillaries. They were demonstrated by smaller swelling of both presynaptic and postsynaptic parts, well-preserved mitochondria, an increased number and regular distribution of synaptic vesicles within axoplasm, and a significantly increased synaptic active zones. However, topiramate used directly after HS was ineffective in the prevention of hyperthermia-evoked synaptic injury. Our findings support the hypothesis that topiramate applied before HS can protect some neocortical synapses via the vascular factor by enhancing blood–brain barrier components and improving the blood supply of gray matter in the temporal lobe, which may be significant in febrile seizure-prevention in children.

Description: How to use environmentally friendly technology to enhance rice field and grain quality is a challenge for the scientific community. Here, we showed that the application of molecular hydrogen in the form of hydrogen nanobubble water could increase the length, width, and thickness of brown/rough rice and white rice, as well as 1000-grain weight, compared to the irrigation with ditch water. The above results were well matched with the transcriptional profiles of representative genes related to high yield, including up-regulation of heterotrimeric G protein β-subunit gene (RGB1) for cellular proliferation, Grain size 5 (GS5) for grain width, Small grain 1 (SMG1) for grain length and width, Grain weight 8 (GW8) for grain width and weight, and down-regulation of negatively correlated gene Grain size 3 (GS3) for grain length. Meanwhile, although total starch content in white rice is not altered by HNW, the content of amylose was decreased by 31.6%, which was parallel to the changes in the transcripts of the amylose metabolism genes. In particular, cadmium accumulation in white rice was significantly reduced, reaching 52% of the control group. This phenomenon was correlated well with the differential expression of transporter genes responsible for Cd entering plants, including down-regulated Natural resistance-associated macrophage protein (Nramp5), Heavy metal transporting ATPase (HMA2 and HMA3), and Iron-regulated transporters (IRT1), and for decreasing Cd accumulation in grain, including down-regulated Low cadmium (LCD). This study clearly showed that the application of molecular hydrogen might be used as an effective approach to increase field and grain quality of rice.

Description: To diagnose chronic kidney disease (CKD) at an early stage, it is important to promote appropriate health guidance and consultation recommendations through regular medical examinations and implementation of continuous high-quality and appropriate treatment. From fiscal year (FY) 2018, Izumo City has initiated the “Izumo City CKD Exacerbation Countermeasures” program. In this study, we aimed to report on the methods undertaken and the effects of this program. Residents aged 40–74 years who underwent specific health checkups from the Izumo City National Health Insurance in FY2018 and FY2019 were included. The rates of CKD re-examination candidates, re-examinations implementation, nephrologist referrals, and health guidance referrals between FY2018 and FY2019 were compared. The rate of CKD re-examination candidates in both years remained unchanged at approximately 7%. The rate of re-examination implementation in FY2019 significantly increased relative to that in FY2018 (p 〈 0.001). Subsequent re-examination candidate trends showed that the rate of nephrologist referrals did not increase. However, the rate of city health guidance referrals significantly increased (p 〈 0.001). Increase in the re-examination and health guidance examination rates indicate improved awareness of CKD among the public and family doctors, and it is expected to prevent CKD exacerbation in the future.

Description: The current work emphasizes the modelling of the electroosmosis-modulated peristaltic flow of Jeffery liquid. Such flows emerge in understanding the movement of biological fluids in a microchannel, such as in targeted drug delivery and blood flow through micro arteries. The non-Newtonian fluid flows inside a non-uniform cross-section and an inclined microchannel. The effects of wall properties and variable fluid properties are considered. The long wavelength and small Re number approximations are assumed to simplify the governing equations. Debye-Hückel linearization is also utilized. The nonlinear governing equations are solved by utilizing the perturbation technique. MATLAB is used for the solution, velocity, temperature, skin friction, coefficient heat transport, concentration, shear wood number, and streamlines expressions. The obtained result in optimal electroosmotic velocity (or Helmholtz-Smoluchowski velocity) increases from −1 to 6; the axial circulation has substantial momentum. For larger optimal electroosmotic velocity, a subsequent boost in an axial electric field causes a significant deceleration. Further, the study helps biomedical engineers to create biomicrofluidics devices that may aid in carrying biological fluids.