Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

Promoting knowledge translation: An ecosystem approach to evidence in health.

The dissemination and implementation of evidence in health contexts have been a concern of several international organizations responsible for recommending actions to health policymakers. World Health Organization has been advocating for an ecosystem of evidence to improve clinical practice and health professional education. Thus, in this article, we address the challenges to developing the evidence ecosystem from the point of view of health professional education, considering the contexts of practice and teaching, focused on knowledge translation. There are three pivotal challenges: producing qualified knowledge; adequate communication of the synthesized evidence; and institutional policy to sustain the implemented evidence in continuous and updated flow. The evidence ecosystem helps to understand these flows between the production and implementation of knowledge, based on the capacity and resources of different health systems. It needs to be developed in the field of health professional education, feedback in the contexts of practice and teaching, to contribute to third-generation knowledge being used by different users of health services.

Drug-induced osteoporosis and mechanisms of bone tissue regeneration through trace elements.

Osteoporosis is associated with an imbalance in bone formation, with certain drugs used in disease treatment being implicated in its development. Supplementation with trace elements may contribute to bone regeneration, offering an alternative approach by enhancing bone mineral density (BMD) and thereby thwarting the onset of osteoporosis. This review aims to assess the mechanisms through which trace elements such as copper (Cu), iron (Fe), selenium (Se), manganese (Mn), and zinc (Zn) are linked to increased bone mass, thus mitigating the effects of pharmaceuticals. Our findings underscore that the use of drugs such as aromatase inhibitors (AIs), proton pump inhibitors (PPIs), antiretrovirals, glucocorticoids, opioids, or anticonvulsants can result in decreased BMD, a primary contributor to osteoporosis. Research indicates that essential elements like Cu, Fe, Se, Mn, and Zn, through various mechanisms, can bolster BMD and forestall the onset of the disease, owing to their protective effects. Consequently, our study recommends a minimum daily intake of these essential minerals for patients undergoing treatment with the aforementioned drugs, as the diverse mechanisms governing the effects of trace elements Cu, Fe, Mn, Se, and Zn facilitate bone remodeling.

Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease?

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.

Therapeutic textiles: A promising approach for human skin dysbiosis?

The close interaction between skin and clothing has become an attractive cornerstone for the development of therapeutic textiles able to alleviate skin disorders, namely those correlated to microbiota dysregulation. Skin microbiota imbalance is known in several skin diseases, including atopic dermatitis (AD), psoriasis, seborrheic dermatitis, rosacea, acne and hidradenitis suppurative (HS). Such microbiota dysregulation is usually correlated with inflammation, discomfort and pruritus. Although conventional treatments, that is, the administration of steroids and antibiotics, have shown some efficacy in treating and alleviating these symptoms, there are still disadvantages that need to be overcome. These include their long-term usage with side effects negatively impacting resident microbiota members, antibiotic resistance and the elevated rate of recurrence. Remarkably, therapeutic textiles as a non-pharmacological measure have emerged as a promising strategy to treat, alleviate the symptoms and control the severity of many skin diseases. This systematic review showcases for the first time the effects of therapeutic textiles on patients with skin dysbiosis, focusing on efficacy, safety, adverse effects and antimicrobial, antioxidant and anti-inflammatory properties. The main inclusion criteria were clinical trials performed in patients with skin dysbiosis who received treatment involving the use of therapeutic textiles. Although there are promising outcomes regarding clinical parameters, safety and adverse effects, there is still a lack of information about the impact of therapeutic textiles on the skin microbiota of such patients. Intensive investigation and corroboration with clinical trials are needed to strengthen, define and drive the real benefit and the ideal biomedical application of therapeutic textiles.

Who are the sexual and gender minorities who frequently interact with children and their association with healthcare. / Quem são as minorias sexuais e de gênero que convivem frequentemente com filhos(as) e sua associação a cuidados em saúde.

This study aimed to examine the sociodemographic profile of sexual and gender minorities who regularly interact with children and investigate whether such frequent interactions are associated with healthcare factors. This cross-sectional study utilized data from the LGBT+ Health Survey in Brazil, conducted online and anonymously from August to November 2020 with 958 participants. Regular interaction with children was defined as living with children or engaging in bi-weekly face-to-face meetings with children residing in different households. Healthcare factors encompass having a professional or reference service, feeling comfortable in discussing personal issues, and receiving worse quality medical or hospital care. The statistical analysis used the Poisson regression with robust variance. The prevalence of interaction with children was 5.3%. We observed a statistically higher prevalence among cisgender women (13.4%) and Black/brown and other non-white people (7.9%) after adjusting for age. The results showed a positive association only between regular interaction with children and worse-quality medical or hospital care received (PR=6.00; 95%CI 1.22-29.67). These findings highlight a persistent stigma and prejudice within healthcare services.

Objetivou-se analisar as características sociodemográficas das minorias sexuais e de gênero que convivem frequentemente com filhos(as) e verificar se existe associação entre convívio frequente com filhos(as) e os cuidados em saúde. Trata-se de um estudo transversal com dados do inquérito de saúde LGBT+, realizado no Brasil em 2020 (agosto-novembro) de forma on-line e anônima, totalizado 958 participantes. O convívio frequente com filhos(as) foi avaliado pela moradia com filhos(as) ou encontros presenciais quinzenais com filhos(as) que moram em outro domicílio. Os cuidados em saúde incluíram ter um profissional ou serviço de referência, sentir-se à vontade para contar seus problemas e receber tratamento médico ou hospitalar de pior qualidade. A regressão de Poisson com variância robusta foi usada na análise estatística. A prevalência de convívio com filhos(as) foi de 5,3%. Após o ajuste por idade, verificou-se uma prevalência estatisticamente maior em mulheres cisgênero (13,4%) e entre pretos/pardos e outras raças/cores não brancas (7,9%). Observou-se que o convívio frequente com filhos(as) foi positivamente associado apenas a receber tratamento médico ou hospitalar de pior qualidade (RP=6,00; IC95% 1,22-29,67). Esses achados destacam que ainda há estigma/preconceito nos serviços de saúde.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Bioenergetic modelling of a marine top predator's responses to changes in prey structure.

Determining how animals allocate energy, and how external factors influence this allocation, is crucial to understand species' life history requirements and response to disturbance. This response is driven in part by individuals' energy balance, prey characteristics, foraging behaviour and energy required for essential functions. We developed a bioenergetic model to estimate minimum foraging success rate (FSR), that is, the lowest possible prey capture rate for individuals to obtain the minimum energy intake needed to meet daily metabolic requirements, for female sperm whale (Physeter macrocephalus). The model was based on whales' theoretical energetic requirements using foraging and prey characteristics from animal-borne tags and stomach contents, respectively. We used this model to simulate two prey structure change scenarios: (1) decrease in mean prey size, thus lower prey energy content and (2) decrease in prey size variability, reducing the variability in prey energy content. We estimate the whales need minimum of ~14% FSR to meet their energetic requirements, and energy intake is more sensitive to energy content changes than a decrease in energy variability. To estimate vulnerability to prey structure changes, we evaluated the compensation level required to meet bioenergetic demands. Considering a minimum 14% FSR, whales would need to increase energy intake by 21% (5-35%) and 49% (27-67%) to compensate for a 15% and 30% decrease in energy content, respectively. For a 30% and 50% decrease in energy variability, whales would need to increase energy intake by 13% (0-23%) and 24% (10-35%) to meet energetic demands, respectively. Our model demonstrates how foraging and prey characteristics can be used to estimate impact of changing prey structure in top predator energetics, which can help inform bottom-up effects on marine ecosystems. We showed the importance of considering different FSR in bioenergetics models, as it can have decisive implications on estimates of energy acquired and affect the conclusions about top predator's vulnerability to possible environmental fluctuations.

Integrated Strategies for Aedes aegypti Control Applied to Individual Houses: An Approach to Mitigate Vectorial Arbovirus Transmission.

Aedes aegypti and Culex quinquefasciatus mosquitoes are vectors of different arboviruses that cause a large burden of disease in humans worldwide. A key step towards reducing the impact of arboviruses on humans can be achieved through integrated mosquito surveillance and control approaches. We carried out an integrated approach of mosquito surveillance and control actions to reduce populations of these insects along with a viral surveillance in a neighborhood of Recife (Northeastern Brazil) with high mosquito densities and arbovirus transmission. The actions were carried out in 40 different houses in the Nova Descoberta neighborhood. The area was divided into two groups, the control group using tools to monitor the mosquito density (1 OVT; 1 Double BR-ovt; monthly capture of alates) and the experimental group with control actions using surveillance tools in an intensified way (2 OVTs; 2 Double BR-ovts; fortnightly capture of alates; toxic baits). We evaluated the study's impact on the mosquito density via the Egg Density (ED) and Adult Density (AD) over a period of 12 cycles of 28 days each. The collected adult mosquitoes were processed via RT-qPCR for DENV, CHIKV and ZIKV and, subsequently, the Minimum Infection Rate (MIR) was calculated. After 12 cycles, we observed a 91% and 99% reduction in Aedes ED and AD in the monitored properties, as well as a 76% reduction in the AD of Cx. quinquefasciatus in the same properties. Moreover, we detected circulating arboviruses (DENV and ZIKV) in 19.52% of captured adult mosquitoes. We show that enhancing entomological surveillance tools can aid in the early detection of possible risk areas based on vector mosquito population numbers. Additionally, the detection of important arboviruses such as ZIKV and DENV raises awareness and allows for a better selection of risk areas and silent virus spread. It offers supplementary information for guiding emergency mosquito control measures in the target area. The goal is to minimize human-vector interactions and, subsequently, to lower the risk of transmitting circulating arboviruses.

Genomic characterisation and dissection of the onset of resistance to acetyl CoA carboxylase-inhibiting herbicides in a large collection of Digitaria insularis from Brazil.

An in-depth genotypic characterisation of a diverse collection of Digitaria insularis was undertaken to explore the neutral genetic variation across the natural expansion range of this weed species in Brazil. With the exception of Minas Gerais, populations from all other states showed high estimates of expected heterozygosity (HE > 0.60) and genetic diversity. There was a lack of population structure based on geographic origin and a low population differentiation between populations across the landscape as evidenced by average Fst value of 0.02. On combining haloxyfop [acetyl CoA carboxylase (ACCase)-inhibiting herbicide] efficacy data with neutral genetic variation, we found evidence of presence of two scenarios of resistance evolution in this weed species. Whilst populations originating from north-eastern region demonstrated an active role of gene flow, populations from the mid-western region displayed multiple, independent resistance evolution as the major evolutionary mechanism. A target-site mutation (Trp2027Cys) in the ACCase gene, observed in less than 1% of resistant populations, could not explain the reduced sensitivity of 15% of the populations to haloxyfop. The genetic architecture of resistance to ACCase-inhibiting herbicides was dissected using a genome wide association study (GWAS) approach. GWAS revealed association of three SNPs with reduced sensitivity to haloxyfop and clethodim. In silico analysis of these SNPs revealed important non-target site genes belonging to families involved in herbicide detoxification, including UDPGT91C1 and GT2, and genes involved in vacuolar sequestration-based degradation pathway. Exploration of five genomic prediction models revealed that the highest prediction power (≥0.80) was achieved with the models Bayes A and RKHS, incorporating SNPs with additive effects and epistatic interactions, respectively.

Investigation of the cytotoxicity, genotoxicity and antioxidant prospects of JM-20 on human blood cells: A multi-target compound with potential therapeutic applications.

JM-20 is a 1,5-benzodiazepine compound fused to a dihydropyridine fraction with different pharmacological properties. However, its potential toxic effects on blood cells have not yet been reported. Thus, the present study aimed to investigate, for the first time, the possible cytotoxicity of JM-20 through cell viability, cell cycle, morphology changes, reactive species (RS) to DCFH-DA, and lipid peroxidation in human leukocytes, its hemolytic effect on human erythrocytes, and its potential DNA genotoxicity using plasmid DNA in vitro. Furthermore, the compound's ability to reduce the DPPH radical was also measured. Human blood was obtained from healthy volunteers (30 ± 10 years old), and the leukocytes or erythrocytes were immediately isolated and treated with different concentrations of JM-20. A cytoprotective effect was exhibited by 10 µM JM-20 against 1 mM tert-butyl hydroperoxide (t-but-OOH) in the leukocytes. However, the highest tested concentrations of the compound (20 and 50 µM) changed the morphology and caused a significant decrease in the cell viability of leukocytes (p < 0.05, in comparison with Control). All tested concentrations of JM-20 also resulted in a significant increase in intracellular RS as measured by DCFH-DA in these cells (p < 0.05, in comparison with Control). On the other hand, the results point out a potent antioxidant effect of JM-20, which was similar to the classical antioxidant α-tocopherol. The IC50 value of JM-20 against the lipid peroxidation induced by (FeII) was 1.051 µM ± 0.21, while the IC50 value of α-tocopherol in this parameter was 1.065 µM ± 0.34. Additionally, 50 and 100 µM JM-20 reduced the DPPH radical in a statistically similar way to the 100 µM α-tocopherol (p < 0.05, in comparison with the control). No significant hemolysis in erythrocytes, no cell cycle changes in leukocytes, and no genotoxic effects in plasmid DNA were induced by JM-20 at any tested concentration. The in silico pharmacokinetic and toxicological properties of JM-20, derivatives, and nifedipine were also studied. Here, our findings demonstrate that JM-20 and its putative metabolites exhibit similar characteristics to nifedipine, and the in vitro and in silico data support the low toxicity of JM-20 to mammals.

Comparative In Vitro Study of the Cytotoxic Effects of Doxorubicin's Main Metabolites on Cardiac AC16 Cells Versus the Parent Drug.

Doxorubicin (DOX; also known as adriamycin) serves as a crucial antineoplastic agent in cancer treatment; however, its clinical utility is hampered by its' intrinsic cardiotoxicity. Although most DOX biotransformation occurs in the liver, a comprehensive understanding of the impact of DOX biotransformation and its' metabolites on its induced cardiotoxicity remains to be fully elucidated. This study aimed to explore the role of biotransformation and DOX's main metabolites in its induced cardiotoxicity in human differentiated cardiac AC16 cells. A key discovery from our study is that modulating metabolism had minimal effects on DOX-induced cytotoxicity: even so, metyrapone (a non-specific inhibitor of cytochrome P450) increased DOX-induced cytotoxicity at 2 µM, while diallyl sulphide (a CYP2E1 inhibitor) decreased the 1 µM DOX-triggered cytotoxicity. Then, the toxicity of the main DOX metabolites, doxorubicinol [(DOXol, 0.5 to 10 µM), doxorubicinone (DOXone, 1 to 10 µM), and 7-deoxydoxorubicinone (7-DeoxyDOX, 1 to 10 µM)] was compared to DOX (0.5 to 10 µM) following a 48-h exposure. All metabolites evaluated, DOXol, DOXone, and 7-DeoxyDOX caused mitochondrial dysfunction in differentiated AC16 cells, but only at 2 µM. In contrast, DOX elicited comparable cytotoxicity, but at half the concentration. Similarly, all metabolites, except 7-DeoxyDOX impacted on lysosomal ability to uptake neutral red. Therefore, the present study showed that the modulation of DOX metabolism demonstrated minimal impact on its cytotoxicity, with the main metabolites exhibiting lower toxicity to AC16 cardiac cells compared to DOX. In conclusion, our findings suggest that metabolism may not be a pivotal factor in mediating DOX's cardiotoxic effects.

Endoscopic Study of Ethmoidal Canals in Cadavers, Including a Histological Analysis of Their Contents.

Introduction The advent of the endoscope has enabled the use of the endonasal approach for a variety of diseases. Studying the ethmoidal canals is important for surgeries of the paranasal sinuses and the anterior base of the skull. Objective To investigate the ethmoidal canals and evaluate their structure, the presence of vessels and nerves, their location, and to perform an anatomopathological study of their contents. Methods We evaluated 20 cadavers (20 left and 20 right nasal cavities) through endoscopic dissection of the anterior base of the skull and exposure of the medial periorbita and dura mater; then, the ethmoidal canals were located and measured in relation to the anterior wall of the sphenoid sinus and between the ethmoidal canals, followed by removal of their content for histological analysis. Results Vessels were present in 75% of the left anterior ethmoidal canals, 70% of the left posterior ethmoidal canals, 75% of the left middle ethmoidal canals, 85% of the right anterior ethmoid canals, and 64.5% of the right posterior ethmoid canals; 50% of the right middle ethmoidal canals contained one vessel. Conclusion The ethmoidal canal does not necessarily contain an ethmoidal artery. Studies with a larger sample should be performed to quantify the correct proportion of arteries and ethmoidal canals.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease.

BACKGROUND: Prevalence of hepatocellular carcinoma (HCC) is increasing, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: To investigate rifaximin (RIF) effects on epigenetic/autophagy markers in animals. METHODS: Adult Sprague-Dawley rats were randomly assigned (n = 8, each) and treated from 5-16 wk: Control [standard diet, water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD), diethylnitrosamine (DEN) in drinking water and Veh gavage], and RIF [HFCD, DEN and RIF (50 mg/kg/d) gavage]. Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained. RESULTS: All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis, and cirrhosis, but three RIF-group did not develop HCC. Comparing animals who developed HCC with those who did not, miR-122, miR-34a, tubulin alpha-1c (Tuba-1c), metalloproteinases-2 (Mmp2), and metalloproteinases-9 (Mmp9) were significantly higher in the HCC-group. The opposite occurred with Becn1, coactivator associated arginine methyltransferase-1 (Carm1), enhancer of zeste homolog-2 (Ezh2), autophagy-related factor LC3A/B (Map1 Lc3b), and p62/sequestosome-1 (p62/SQSTM1)-protein. Comparing with controls, Map1 Lc3b, Becn1 and Ezh2 were lower in HCC and RIF-groups (P < 0.05). Carm1 was lower in HCC compared to RIF (P < 0.05). Hepatic expression of Mmp9 was higher in HCC in relation to the control; the opposite was observed for p62/Sqstm1 (P < 0.05). Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control (P = 0.024). There was no difference among groups for Tuba-1c, Aldolase-B, alpha-fetoprotein, and Mmp2 (P > 0.05). miR-122 was higher in HCC, and miR-34a in RIF compared to controls (P < 0.05). miR-26b was lower in HCC compared to RIF, and the inverse was observed for miR-224 (P < 0.05). There was no difference among groups regarding miR-33a, miR-143, miR-155, miR-375 and miR-21 (P > 0.05). CONCLUSION: RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

High red meat consumption among PNPLA3 polymorphism carriers is associated with NAFLD in a multi-center cross-sectional study.

BACKGROUND & AIM: Patatin-like phospholipase domain-containing 3 gene (PNPLA3) polymorphism has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD), with evidence for potential interaction with nutrition. However, the combination of meat consumption with genetic polymorphism has not been tested. Therefore, this study aims to test the association between the joint presence of PNPLA3 rs738409 G-allele with high meat consumption and NAFLD in populations with diverse meat consumption. METHODS: A cross-sectional study among Israeli screening and Brazilian primary healthcare populations. Food consumption was assessed by a food-frequency questionnaire. PNPLA3 polymorphism was defined as homozygous (GG) or heterozygous (GC). Inconclusive/probable NAFLD was defined as a fatty liver index (FLI) ≥ 30 and probable NAFLD as FLI ≥ 60. RESULTS: The sample included 511 subjects from the screening and primary healthcare populations (n = 213 and n = 298, respectively). Genetic polymorphism (homozygous GG or heterozygous GC) combined with high consumption of total meat, red and/or processed meat, unprocessed red meat, and processed meat was associated with the highest odds for inconclusive/probable NAFLD (OR = 2.75, 95%CI 1.27-5.97, p = 0.011; OR = 3.24, 1.43-7.34, p = 0.005; OR = 2.92, 1.32-6.47, p = 0.008; OR = 3.16, 1.46-6.83, p = 0.003, respectively), adjusting for age, gender, BMI, alcohol consumption, carbohydrate, and saturated fat intake. In addition, genetic polymorphism combined with high processed meat consumption was associated with the highest odds for probable NAFLD (OR = 2.40, 95%CI 1.04-5.56, p = 0.040). CONCLUSIONS: High red meat intake may confer a greater risk for NAFLD among PNPLA3 polymorphism carriers. Prospective studies are needed to confirm these findings and consider minimizing red and processed meat consumption among PNPLA3 polymorphism carriers.

Low back pain, pelvic pain, and associated factors in type 1 diabetic pregnant women.

INTRODUCTION: Pregnancy and diabetes mellitus promote several musculoskeletal changes predisposing this population to complaints of Lower Back (LB) and Pelvic Pain (PP). OBJECTIVE: To assess the frequency of LB and PP and associated factors in type 1 Diabetic (DM1) pregnant women. METHOD: An observational analytical cross-sectional study. Thirty-six pregnant women with DM1 were evaluated through a postural assessment with a focus on pelvic positioning and what patients reported. The associated factors were assessed using the State-Trait Anxiety Inventory (STAI), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Female Sexual Function Index (FSFI). RESULTS: The frequency of LB and PP was 55.6 % and 30.6 %, respectively. The presence of anxiety was not associated with a higher prevalence of pain. The incidence of sexual dysfunctions was higher in the GD. DM1 duration had a mean of 14.9 years (± 8.2 SD) in the GD and 9.0 years (± 6.9 SD) in the GSD, which was statistically significant (p ≤ 0.050). In the multiple binary regression analysis for the occurrence of pain, the independent factor was DM1 duration ≥ 17 years (OR = 11.2; 95 % CI = 1.02‒124.75). The association between DM1 duration ≥ 17 years and being overweight showed a probability of 95 % for the studied population in the analysis of the probabilities of occurrence of the pain event. CONCLUSION: There was a high frequency of LB and PP related to pregnancy in DM1 pregnant women in the second trimester of pregnancy. The incidence of sexual dysfunction and DM1 duration ≥ 17 years increases the chance that DM1 pregnant women will experience pain. There was no association between anxiety. urinary incontinence and pain in DM1 pregnant women.

A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

Impact of frailty and sex-related differences on postural control and gait in older adults with Parkinson's Disease.

BACKGROUND: Parkinson's Disease (PD), a neurodegenerative condition, affects normal aging and leads to reduced motor abilities. In addition, frailty syndrome can increase vulnerability and risks of undesirable effects such as disease progression, falls, disability, and premature death among individuals with PD. AIMS: To assess the impact of frailty on balance and gait parameters in older with PD and to determine if sex mediates these measures. METHODS: Twenty-seven (27) participants (n = 18 men; n = 10 frail) performed 4 balance tasks on a force platform (eyes opened/closed in bipodal/semi-tandem position) while linear center of pressure (COP) parameters were calculated. Participants also performed two different speed walks on a gait analysis system to assess gait parameters. RESULTS: Significant differences between the frail and non-frail group were observed on postural control (mainly for area of COP p = 0.013/d = 0.47/70 %; sway velocity p = 0.048/d = 0.41/23 %) where frail reported poor balance. No significant sex differences were reported for postural control. Gait analysis was comparable between frail and non-frail, while significant differences between men and women were observed for step length (p = 0.002, d = 0.71), step width (p = 0.001, d = 0.75) and base of support (p = 0.012, d = 0.64) variables. CONCLUSION: Frail Parkinson's individuals present poorer postural control than non-frail individuals, but comparable gait parameters. Men and women are comparable on postural control but show different gait parameters. These results may have implications in clinical decision-making in rehabilitation for frailty in older adults, men and women with Parkinson's disease when balance and gait are of concern.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.