Parenting practices as a buffer in the relationship between exposure to community violence and bullying in Mexican adolescents.

Multiple studies have shown that adolescents exposed to community violence are likely to engage in bullying behaviors. However, we still need to understand which variables can help reduce the influence of community violence exposure (CVE) on bullying. To investigate this question, a study was conducted with a sample of 568 Mexican adolescents, comprising 276 (48.6%) males and 292 (51.4%) females aged 12 to 16 years old (M age = 13.7 years, SD = 0.82). The study examined how parental support (PS) and parental induction to justice sensitivity (JS) can moderate the relationship between CVE and bullying. The study used structural equation modeling with latent variables. The results showed that CVE was positively associated with bullying, whereas PS and the induction to perpetrator JS were negatively associated. The moderation analysis suggests that the relationship between CVE and bullying was weaker among adolescents who received high PS. On the other hand, low and high parental induction to JS had the same moderating effect. Based on the findings, parental practices are critical when developing preventive programs to reduce the harmful effects of CVE on bullying behavior.

Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial.

The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = -34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

CHALLENGES IN PSORIASIS RESEARCH: A SYSTEMATIC REVIEW OF PRECLINICAL MODELS.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells.The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two- and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

Measurement properties of the Foot Function Index (FFI) questionnaire: A systematic review.

OBJECTIVE: Large numbers of people are subject to alterations and pathologies in the foot. To quantify how these problems of foot function affect the quality of life, clinicians and researchers have developed measures such as the Foot Function Index (FFI). Our aim is to determine the methodological quality of the FFI including adaptations to other languages. DATA SOURCES: The studies considered in this review were extracted from the PubMed, Embase and CINAHL databases. The inclusion criteria were followed: (1) studies of patients with no previous foot or ankle pathology and aged over 18 years; (2) based on English-language patient-reported outcome measures that assess foot function; (3) the patient-reported outcome measures should present measurement properties based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria. REVIEW METHODS: The systematic review was conducted following the COSMIN criteria to establish the methodological quality of the original FFI, together with its variants and adaptations. The last search was carried out in May 2024. RESULTS: Of the 1994 studies obtained in the preliminary search, 20 were eligible for inclusion in the final analysis. These results are the validations and cross-cultural adaptations to the following languages: the original FFI has cross-cultural adaptation in 13 languages and the FFI-Revised Short Form has been adapted and validated for use in 2 languages. CONCLUSION: In terms of methodological quality, the FFI-Revised Short Form questionnaire is a valuable instrument for evaluating ankle and foot function and could usefully be expanded to be available in more languages.

A Systematic Review of the Relationship between Social Isolation and Physical Health in Adults.

Background: According to the World Health Organization, social isolation, particularly of older adults, is a public health issue endangering the well-being of individuals, families, and communities. Social isolation affects health through biological, behavioral, and psychological pathways and is associated with physical and psychological/emotional well-being, increases morbidity and mortality rates, and lowers quality of life. Purpose: This systematic review examined the relationship between social isolation and physical health, including subjective and objective dimensions, and factors that influence this relationship in adults. Methods: This systematic review examined six electronic databases covering the field of health and human services and included results from 1 January 2017 to 10 March 2023 with key terms including adult social connection or social isolation coupled with health, physical, psychological, emotional, mental, or behavioral. The initial search yielded 925 research articles across all databases and was narrowed to 710 when the decision was made to focus on social isolation and physical health. Covidence was used throughout the retrieval and appraisal process, as provided in a PRISMA flow diagram. Twenty-four studies that scored 90 or above in the appraisal process were included in the systematic review. Results: The studies represented included seven studies conducted in the United States and seventeen studies conducted internationally. Regarding study design, twenty-three studies were quantitative, one was qualitative, and one was mixed methods. The majority of quantitative studies were correlational in design with nine being longitudinal. The majority of studies were based on large national data sets representing in total 298,653 participants aged 50 and older. The results indicate that social isolation is related to increases in inflammatory biomarkers associated with diseases, all-cause mortality, lower expectations of longevity, and frailty. In addition, social isolation was associated with cognitive decline and disruptions in sleep. Poor oral health increased social isolation. The results further indicated that decreased physical performance/function and a decline in physical activity were associated with social isolation, as well as decreased overall physical health, poor health behaviors, and self-care, and decreased health-related quality of life. Further research is warranted to examine the possible bidirectionality of these relationships and possible mediating, moderating, or confounding variables. Implications: Future research is needed to explore the biological and behavioral pathways in which social isolation negatively impacts physical health. Going forward, studies are needed that move beyond descriptive, exploratory methods and integrate data from qualitative and mixed-method designs that will inform the development and testing of a conceptual framework related to social isolation and health. By advancing the science behind social isolation, comprehensive interventions can be identified and tested with implications at the individual, family, community, and societal levels to reduce social isolation, particularly among adults, and improve health and quality of life.

Alleviating Heat Stress in Fattening Pigs: Low-Intensity Showers in Critical Hours Alter Body External Temperature, Feeding Pattern, Carcass Composition, and Meat Quality Characteristics.

Heat stress is a significant environmental problem that has a detrimental impact on animal welfare and production efficiency in swine farms. The current study was conducted to assess the effect of low-intensity showers, provided during critical high-temperature hours daily, on body external temperature, feeding pattern, and carcass and meat quality characteristics in fattening pigs. A total of 400 animals (200 barrows and 200 gilts) were randomly allotted in 40 pens. A shower nozzle was installed over 20 pens (half barrows and half gilts) where pigs received a low-intensity shower for 2 min in 30 min intervals from 12 to 19 h (SHO group). Another group without showers was also considered (CON). Feeder occupancy measurement, thermographic measures, and carcass and meat quality parameters were studied. In the periods with higher environmental temperatures, SHO animals showed an increase in the feeder occupancy rate compared to the CON group. A decrease in temperature was observed after the shower, regardless of the anatomical location (p < 0.005). The treatment with showers led to higher values than in the CON group of 4.72%, 3.87%, 11.8%, and 15.1% for hot carcass weight, lean meat yield, and fat thickness in Longissimus Dorsi (LD) and Gluteus Medius muscles, respectively (p < 0.01). Pork from CON showed a 14.9% higher value of drip loss, and 18.9% higher malondialdehyde concentration than SHO (p < 0.01); meanwhile, intramuscular fat content was 22.8% higher in SHO than in CON (p < 0.01). On the other hand, the CON group exhibited higher L* (2.13%) and lower a* and b* values (15.8% and 8.97%) compared to the SHO group. However, the pH20h of the CON group was significantly lower than that of the SHO group (p < 0.001), indicating a softer pH decrease. Related to fatty acids in subcutaneous outer and inner layers and intramuscular fat, the CON group showed higher ΣSFA and lower ΣMUFA and Δ9-desaturase indexes than SHO (p < 0.05). In conclusion, the amelioration of heat stress through showers at critical times should be considered an interesting tool that improves both carcass and meat quality, as well as animal welfare.

Eating disorder symptoms and weight pressure in female rowers: associations between self-concept, psychological well-being and body composition.

BACKGROUND: Female rowers may be at risk of eating disorders and high weight pressure. AIM: The purpose of the study was to investigate the prevalence of disordered eating symptoms and weight-related pressure and the associations with self-concept, psychological well-being, socio-demographic data, experience, performance level and body composition in female fixed-bench rowers. METHODS: Female rowers (n = 208; age ranged mean ± SD 23.6 ± 6.5 years) completed the SCOFF scale, Weight-Pressures in Sport-Females (WPS-F), Physical Self-Concept Questionnaire and the Ryff scales of psychological well-being and provided information on their experience and level of competition. In a subgroup of 115 athletes, body composition was assessed using bioimpedance. RESULTS: It was found that 42.3% of the athletes scored ≥ 2 on SCOFF and mean ± SD value of WPS-F score was 3.65 ± 0.82. Stepwise regression analysis revealed that self-concept of strength and pressure from teammates and the uniform were associated with higher ED symptoms, whereas better psychological well-being in terms of autonomy, self-concept of attractiveness, and age were protective factors for ED symptoms. BMI, athletes' physical condition, strength, and experience were associated with more weight-related pressure and better self-concept of attractiveness and physical well-being of autonomy were significantly associated with less pressure. In body composition analysis, higher extra cellular water, self-acceptance, and physical condition were associated with more weight-related pressure in female rowers, being attractiveness and the environmental mastery protective elements. CONCLUSIONS: The prevalence of ED symptomatology and weight-related pressure are high in female fixed bench rowing. The psychological factors of well-being and self-concept, team environment, body image concerns and body composition analysis should be considered to promote healthy eating behaviours in female rowers.

Athletes may be at increased risk of developing disordered eating behaviours that, if persistent, may lead to a diagnosis of an eating disorder. This can affect their health in the short and long term. The risk factors are many, and perceived weight-related pressures and psychological attitudes towards body image, appearance and concerns are less well understood. Female rowers are at high risk for eating disorder symptoms, and athletes' self-concept of strength and pressure from teammates and the uniform were associated as negative factors for eating disorder symptoms. On the other hand, better psychological well-being in terms of autonomy, self-concept of attractiveness and age were protective factors for eating disorder symptoms. Weight pressure was associated with higher body mass index, water retention, physical condition, strength and experience, whereas better self-concept of attractiveness and physical well-being were significantly associated with less pressure. Weight pressure and psychological attitudes towards body image have the role of protective/facilitating factors against the development of eating disorders. They should be taken into account when designing prevention and intervention programmes for athletes, coaches, parents and technical staff.

Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study.

Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.

Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project. Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m2; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease. Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) (P = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P < 0.05). These vascular changes were independent of differences in age. Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health.

Is family meal frequency associated with obesity in children and adolescents? A cross-sectional study including 155 451 participants from 43 countries.

OBJECTIVE: This study tried to examine the association between the frequency of family meals and excess weight using large and representative samples of children and adolescents from 43 countries. METHODS: This cross-sectional study used data from the Health Behaviour in School-aged Children (HBSC), which included nationally representative samples of children and adolescents aged 10-17 years, involving a total of 155 451 participants (mean age = 13.6 years; standard deviation [SD] = 1.6; 51.4% girls). Family meal frequency was gauged through the following question: 'How frequently do you and your family typically share meals?' The possible responses were: 'never', 'less often', 'approximately once a week', 'most days' and 'every day'. The body weight and height of the participants were self-reported and utilized to calculate body mass index (BMI). Subsequently, BMI z-scores were computed based on the International Obesity Task Force criteria, and the prevalence of excess weight was defined as +1.31 SD for boys and + 1.24 SD for girls, with obesity defined as +2.29 SD for boys and + 2.19 SD for girls. Generalized linear mixed models were conducted to examine the associations between the frequency of family meals and excess weight or obesity. RESULTS: The lowest predicted probabilities of having excess weight and obesity were observed for those participants who had family meals every day (excess weight: 34.4%, 95% confidence interval [CI] 31.4%-37.5%; obesity: 10.8%, 95% CI 9.0%-13.0%). CONCLUSIONS: A higher frequency of family meals is associated with lower odds of having excess weight and obesity in children and adolescents.

Aetiology, epidemiology and treatment of musculoskeletal injuries in badminton players: a systematic review and meta-analysis.

The present study has two main goals: to conduct a systematic review of musculoskeletal injuries experienced by badminton players, and to examine the management of such injuries. Searches were conducted of the PROSPERO, PubMed, Scopus, and SPORTDiscus databases, from their inception until March 2023. The papers analysed were all based on a study population consisting of individuals aged 18 years or more, diagnosed with badminton-related injuries. The methodological quality assessments was using the Newcastle-Ottawa Scale and REVMAN. A total of 28 studies were included in the systematic review. In total, the analysis included 2435 participants. Of these athletes, 35.6% (1012) were female and 64.4% (1503) were male. By type of injury, sprains were the most commonly studied and the most prevalent, accounting for 36.06% of the sample. These were followed by muscle injuries, representing 23.86% of the total. Injuries to the joints were the least prevalent, accounting for 4.97% of the sample. Lower limb injuries accounted for 52.15% of the total. Of these, ankle injuries were the most common. Despite the generally low quality of the studies considered, the evidence suggests that musculoskeletal injuries, especially to the lower limb, most commonly affect badminton players of all levels.

Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.

Introduction: The pathogenesis of Post-Transplant Diabetes Mellitus (PTDM) is complex and multifactorial and it resembles that of Type-2 Diabetes Mellitus (T2DM). One risk factor specific to PTDM differentiates both entities: the use of immunosuppressive therapy. Specifically, Tacrolimus interacts with obesity and insulin resistance (IR) in accelerating the onset of PTDM. In a genotypic model of IR, the obese Zucker rats, Tacrolimus is highly diabetogenic by promoting the same changes in beta-cell already modified by IR. Nevertheless, genotypic animal models have their limitations and may not resemble the real pathophysiology of diabetes. In this study, we have evaluated the interaction between beta-cell damage and Tacrolimus in a non-genotypic animal model of obesity and metabolic syndrome. Methods: Sprague Dawley rats were fed a high-fat enriched diet during 45 days to induce obesity and metabolic dysregulation. On top of this established obesity, the administration of Tacrolimus (1mg/kg/day) during 15 days induced severe hyperglycaemia and changes in morphological and structural characteristics of the pancreas. Results: Obese animals administered with Tacrolimus showed increased size of islets of Langerhans and reduced beta-cell proliferation without changes in apoptosis. There were also changes in beta-cell nuclear factors such as a decrease in nuclear expression of MafA and a nuclear overexpression of FoxO1A, PDX-1 and NeuroD1. These animals also showed increased levels of pancreatic insulin and glucagon. Discussion: This model could be evidence of the relationship between the T2DM and PTDM physiopathology and, eventually, the model may be instrumental to study the pathogenesis of T2DM.

Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. METHODS: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. RESULTS: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024). CONCLUSIONS: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease. TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en . CLINICALTRIALS: gov number, NCT00924937.

Plants from Arid and Semi-Arid Zones of Mexico Used to Treat Respiratory Diseases: A Review.

Medicinal plants have been a traditional remedy for numerous ailments for centuries. However, their usage is limited due to a lack of evidence-based studies elucidating their mechanisms of action. In some countries, they are still considered the first treatment due to their low cost, accessibility, and minor adverse effects. Mexico is in second place, after China, in inventoried plants for medicinal use. It has around 4000 species of medicinal plants; however, pharmacological studies have only been carried out in 5% of its entirety. The species of the Mexican arid zones, particularly in semi-desert areas, exhibit outstanding characteristics, as their adverse growing conditions (e.g., low rainfall and high temperatures) prompt these plants to produce interesting metabolites with diverse biological activities. This review explores medicinal plants belonging to the arid and semi-arid zones of Mexico, focusing on those that have stood out for their bioactive potential, such as Jatropha dioica, Turnera diffusa, Larrea tridentata, Opuntia ficus-indica, Flourensia cernua, Fouquieria splendes, and Prosopis glandulosa. Their extraction conditions, bioactive compounds, mechanisms of action, and biological efficacy are presented, with emphasis on their role in the treatment of respiratory diseases. Additionally, current research, novel applications, and perspectives concerning medicinal plants from these zones are also discussed.

Antimicrobial Activity of Bacillus amyloliquefaciens BS4 against Gram-Negative Pathogenic Bacteria.

Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.

Fish skin grafts versus standard of care on wound healing of chronic diabetic foot ulcers: A systematic review and meta-analysis.

INTRODUCTION: This study will explore the effectiveness of fish skin grafts (FSG) in ulcer healing in diabetic foot disease compared to standard of care (SOC). METHODS: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. RESULTS: Five randomised controlled trials (RCTs) with a total of 411 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving fish skin grafts (OR = 3.34, 95% CI 2.14-5.20, p < 0.01, I2 = 0%) compared to control groups. CONCLUSION: Fish skin grafts have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in diabetic foot disease.

Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase.

Chagas disease is one of the world's neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, d-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based high-throughput screening (HTS) campaign of 13,040 compounds. The selection criteria were based on first determining which compounds strongly inhibited TcGlcK in a primary screen, followed by establishing on-target confirmed hits from a confirmatory assay. Compounds that exhibited notable in vitro trypanocidal activity over the T. cruzi infective form (trypomastigotes and intracellular amastigotes) co-cultured in NIH-3T3 mammalian host cells, as well as having revealed low NIH-3T3 cytotoxicity, were further considered. Compounds GLK2-003 and GLK2-004 were determined to inhibit TcGlcK quite well with IC50 values of 6.1 µM and 4.8 µM, respectively. Illuminated by these findings, we herein screened a small compound library consisting of thirteen commercially available 3-nitro-2-phenyl-2H-chromene analogues, two of which were GLK2-003 and GLK2-004 (compounds 1 and 9, respectively). Twelve of these compounds had a one-point change from the chemical structure of GLK2-003. The analogues were run through a similar primary screening and confirmatory assay protocol to our previous HTS campaign. Subsequently, three in vitro biological assays were performed where compounds were screened against (a) T. cruzi (Tulahuen strain) infective form co-cultured within NIH-3T3 cells, (b) T. brucei brucei (427 strain) bloodstream form, and (c) NIH-3T3 host cells alone. We report on the TcGlcK inhibitor constant determinations, mode of enzyme inhibition, in vitro antitrypanosomal IC50 determinations, and an assessment of structure-activity relationships. Our results reveal that the 3-nitro-2-phenyl-2H-chromene scaffold holds promise and can be further optimized for both Chagas disease and human African trypanosomiasis early-stage drug discovery research.

Targeting strategies with lipid vectors for nucleic acid supplementation therapy in Fabry disease: a systematic review.

Fabry disease (FD) results from a lack of activity of the lysosomal enzyme α-Galactosidase A (α-Gal A), leading to the accumulation of glycosphingolipids in several different cell types. Protein supplementation by pDNA or mRNA delivery presents a promising strategy to tackle the underlying genetic defect in FD. Protein-coding nucleic acids in FD can be either delivered to the most affected sites by the disease, including heart, kidney and brain, or to specialized organs that can act as a production factory of the enzyme, such as the liver. Lipid-based systems are currently at the top of the ranking of non-viral nucleic acid delivery systems, and their versatility allows the linking to the surface of a wide range of molecules to control their biodistribution after intravenous administration. This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines and provides an overview and discussion of the targeting ligands that have been employed so far to actively vectorize intravenously administered non-viral vectors based on lipid carriers to clinically relevant organs in the treatment of FD, for protein-coding nucleic acid (pDNA and mRNA) supplementation. Among the thirty-two studies included, the majority focus on targeting the liver and brain. The targeting of the heart has been reported to a lesser degree, whereas no articles addressing kidney-targeting have been recorded. Although a great effort has been made to develop organ-specific nucleic acid delivery systems, the design of active-targeted carriers with high quality, good clinical translation, and large-scale manufacturing capacity is still challenging.