Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials.

INTRODUCTION: Empagliflozin is a sodium-glucose co-transporter-2 inhibitor used to treat type 2 diabetes (T2D) to improve glycemic control, reduce risk of cardiovascular death in patients with T2D, and treat patients with symptomatic chronic heart failure (HF) and chronic kidney disease (CKD). The safety profile of empagliflozin is well documented, although adverse events (AEs) remain of interest to clinicians. This study provides an up-to-date safety evaluation of empagliflozin. METHODS: Data were pooled from four long-term trials which included: patients with T2D and established cardiovascular disease (EMPA-REG OUTCOME), patients with HF, with/without diabetes (EMPEROR-Reduced and EMPEROR-Preserved), and patients with CKD, with/without diabetes (EMPA-KIDNEY). Since three of the four trials evaluated empagliflozin 10 mg, the meta-analysis was restricted to this dose. RESULTS: Total trial medication exposure was 19,727 patient-years for patients who received empagliflozin (n = 10,472) and 19,447 patient-years for placebo (n = 10,461). The percentages of patients with serious AEs, fatal AEs, and AEs leading to discontinuation were similar for both groups. The incidences of serious urinary tract infection and serious pyelonephritis or urosepsis were similar for both groups but higher for women taking empagliflozin versus placebo. Serious genital infections were not increased with empagliflozin versus placebo. There was a slight increase in ketoacidosis and serious volume depletion in patients who received empagliflozin versus placebo. The occurrence of serious acute kidney injury was lower with empagliflozin versus placebo. Empagliflozin was not associated with an increased incidence of severe hypoglycemia, bone fractures, or lower limb amputations. Empagliflozin is therefore considered safe in people without diabetes, the elderly, patients with very low estimated glomerular filtration rate, low body mass index, and HF. Safety is unaltered by blood pressure, concomitant medication for hypertension, HF, and immunosuppression. CONCLUSION: This meta-analysis of long-term safety data extends current knowledge and confirms the safety and tolerability of empagliflozin.

Empagliflozin is used in adults with type 2 diabetes mellitus (T2D) to improve blood glucose control and in people with T2D and established cardiovascular disease to reduce the risk of death from cardiovascular disease. Also, it is used to treat people with chronic heart failure or chronic kidney disease. Although many clinical trials have shown the effectiveness and safety of empagliflozin, the evaluation of adverse events (AEs) remains of interest. This study further examined the safety of empagliflozin by analyzing four large, long-term clinical trials. These trials included over 20,900 patients with T2D and established cardiovascular disease, patients with heart failure, and patients with chronic kidney disease. Adverse events of interest were pooled and analyzed. Results show the risk of the investigated AEs was similar whether patients had received empagliflozin or placebo. The risk of urinary tract infections, including those that spread to the kidneys, was higher for women taking empagliflozin versus placebo. Ketoacidosis was rare but more frequent in patients taking empagliflozin. A reduction in blood volume was slightly more frequent in people taking empagliflozin versus placebo. The risk of kidney injury was reduced in patients taking empagliflozin versus placebo. The risk of genital infections, hypoglycemia, bone fractures, or lower limb amputations was not increased with empagliflozin. No new safety concerns were raised, including in people who were elderly, had kidney disease, low body weight, T2D, or heart failure. This analysis is consistent with current knowledge of empagliflozin safety in a broad range of patients.

Complex multimorbidity in hemodialysis patients: Study in a metropolitan region in Brazil.

The objective of this article was to analyze the factors associated with complex multimorbidity (CMM) among hemodialysis patients in a metropolitan region in southeastern Brazil. To this end, a cross-sectional epidemiological survey was carried out with 1,024 individuals in the year 2019. CMM data were collected through the application of a questionnaire to hemodialysis patients. The binary logistic regression model was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) between independent variables and CMM. The prevalence of CMM was 81% and the results indicated that: living in cities with a low rate of general mortality (OR = 0.395, 95%CI = 0.179-0.870), being aged between 18 and 29 (OR = 0.402, 95%CI = 0.196-0.825), having an elementary education (OR = 0.536, 95%CI = 0.290-0.966) and assessing health as good/very good (OR = 0.446, 95%CI = 0.301-0.661) are factors that reduced the chances of having CMM, whereas a longer period of hemodialysis (OR = 1.779 and 95%CI = 1.057-2.997) increased the chances of CMM. The findings show that characteristics of the social and individual context are associated with CMM in hemodialysis patients, signaling the need for public health policies that include monitoring the complex multimorbidity condition among individuals undergoing hemodialysis treatment.

A brief description of the epidemiology of dengue in Dili, Timor-Leste, 2018-2022.

Abstract: Dengue virus (DENV) infection causes 390 million infections per year and 40,000 deaths globally. It is endemic in many countries in Asia, Africa, the Americas, the Caribbean, and Oceania. Dengue is endemic in Timor-Leste year-round, but peak transmission occurs during the rainy season. We briefly describe the epidemiology of DENV in the Municipality of Dili between 2018 and 2022. There were 6,234 cases notified, with a mean annual incidence rate of 330 cases per 100,000 population. There were 55 deaths (case fatality rate 0.9%). The peak annual incidence (3,904 cases) occurred in 2022 after an outbreak was declared in January of that year; this outbreak included 760 cases of dengue haemorrhagic fever and 35 deaths. The number of outbreak cases requiring hospital treatment exceeded the usual capacity, but facilities established for coronavirus disease 2019 (COVID-19) isolation and treatment were repurposed to meet this demand. Existing strategies of vector control, minimising breeding sites and promoting early presentation for treatment should continue, as should the utilisation of surveillance systems and treatment facilities established during the COVID-19 pandemic. However, dengue incidence remains high, and other dengue control strategies-including the deployment of Wolbachia-infected mosquitoes-should be considered in Timor-Leste.

The first confirmed outbreak of chikungunya reported in Timor-Leste, 2024.

Abstract: Timor-Leste is a mountainous, half-island nation with a population of 1.3 million, which shares a land border with Indonesia and is 550 km from Darwin, Australia. Since independence in 2002, Timor-Leste has achieved significant development; however, high levels of poverty remain. Chikungunya virus (CHIKV) is endemic in over 100 countries in Africa, Asia, Europe and in the Americas. It is transmitted by the bite of infected Aedes aegypti or Ae. albopictus mosquitoes, which are present in Timor-Leste and which contribute to annual rainy-season dengue virus (DENV) outbreaks. Symptomatic people typically suffer from acute onset of fever, usually accompanied by severe arthritis or arthralgia. Joint pain can be debilitating for several days, and may sometimes last for weeks, months or years. Unlike DENV infection which has significant mortality, most people recover completely. Between 2002 and 2023, there were 26 cases of CHIKV notified in Australia who acquired their infection in Timor-Leste; however, laboratory testing capability for CHIKV in Timor-Leste only became available in 2021 using polymerase chain reaction (PCR). The first locally diagnosed case was notified in November 2023. In January 2024, an outbreak of CHIKV was recognised in Timor-Leste for the first time, with 195 outbreak cases reported during 1-31 January 2024; all were PCR positive. There were no cases hospitalised, and no deaths. The median age of cases was 17 years (range 1-76 years); 51% were males. Cases were reported across the country; most (88/195) were from Dili, although the highest incidence was seen in the neighbouring municipality of Ermera (monthly incidence rate of 58.8 cases per 100,000 population). This first reported outbreak of CHIKV in Timor-Leste highlights the need for improved mosquito-borne illness control and response strategies, including minimising breeding sites and promoting early presentation for treatment and differential diagnosis from DENV, and consideration of the deployment of Wolbachia-infected mosquitoes, particularly as they have shown to reduce the transmission of CHIKV, DENV and Zika virus, all of which pose threats in Timor-Leste.

Dynamics of the Trypanosoma cruzi infection in adipose tissue: Assessing gene expression of PNPLA2, FASN, and ACAT1 under Benzonidazole treatment and indirect mononuclear immune cells interaction.

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.

Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study.

BACKGROUND: Lower socioeconomic position (SEP) associates with adverse pregnancy and perinatal outcomes and with less favourable metabolic profile in nonpregnant adults. Socioeconomic differences in pregnancy metabolic profile are unknown. We investigated association between a composite measure of SEP and pregnancy metabolic profile in White European (WE) and South Asian (SA) women. METHODS: We included 3,905 WE and 4,404 SA pregnant women from a population-based UK cohort. Latent class analysis was applied to nineteen individual, household, and area-based SEP indicators (collected by questionnaires or linkage to residential address) to derive a composite SEP latent variable. Targeted nuclear magnetic resonance spectroscopy was used to determine 148 metabolic traits from mid-pregnancy serum samples. Associations between SEP and metabolic traits were examined using linear regressions adjusted for gestational age and weighted by latent class probabilities. RESULTS: Five SEP sub-groups were identified and labelled 'Highest SEP' (48% WE and 52% SA), 'High-Medium SEP' (77% and 23%), 'Medium SEP' (56% and 44%) 'Low-Medium SEP' (21% and 79%), and 'Lowest SEP' (52% and 48%). Lower SEP was associated with more adverse levels of 113 metabolic traits, including lower high-density lipoprotein (HDL) and higher triglycerides and very low-density lipoprotein (VLDL) traits. For example, mean standardized difference (95%CI) in concentration of small VLDL particles (vs. Highest SEP) was 0.12 standard deviation (SD) units (0.05 to 0.20) for 'Medium SEP' and 0.25SD (0.18 to 0.32) for 'Lowest SEP'. There was statistical evidence of ethnic differences in associations of SEP with 31 traits, primarily characterised by stronger associations in WE women e.g., mean difference in HDL cholesterol in WE and SA women respectively (vs. Highest-SEP) was -0.30SD (-0.41 to -0.20) and -0.16SD (-0.27 to -0.05) for 'Medium SEP', and -0.62SD (-0.72 to -0.52) and -0.29SD (-0.40 to -0.20) for 'Lowest SEP'. CONCLUSIONS: We found widespread socioeconomic differences in metabolic traits in pregnant WE and SA women residing in the UK. Further research is needed to understand whether the socioeconomic differences we observe here reflect pre-conception differences or differences in the metabolic pregnancy response. If replicated, it would be important to explore if these differences contribute to socioeconomic differences in pregnancy outcomes.

Biomedical and Biotechnological Potential of Animal Venoms: Bothrops Snake Venoms and their Antimicrobial Applications.

The pursuit of novel treatment alternatives to address the accumulated resistance to antimicrobials over the years has prompted the scientific community to explore biodiversity, particularly animal venom, as a potential source of new antimicrobial drugs. Snake venoms, with their complex mixtures of components, are particularly promising targets for investigation in this regard. The search for novel molecules exhibiting antimicrobial activity against multidrug-resistant strains is of paramount importance for public health and numerous research groups worldwide. High expectations within the healthcare field are supported by the scientific literature, which highlights the potential development of innovative drugs through in vivo and in vitro application, depending on dose titration. Snake venoms and their molecules and peptides offer exponential possibilities for biotechnological applications as antimicrobial agents. However, many uncertainties and unexplored avenues remain, presenting opportunities for discoveries and research.

Association between Urinary Sodium Excretion and Body Fat in School-Aged Children: Insights from the ARIA Study.

Childhood obesity has been associated with increased sodium intake. Nonetheless, evidence linking sodium intake to Body Mass Index (BMI) and Body Fat Mass Percentage (%BF) remains limited, especially in the pediatric age group. Therefore, this study aims to investigate whether there is an association between 24 h urinary sodium excretion with BMI and %BF in a sample group of children from the ARIA study. This cross-sectional analysis included 303 children aged 7 to 12 from across 20 public schools in Porto, Portugal. Weight and %BF were assessed using the Tanita™ BC-418 Segmental Body Analyzer. Children's Total Energy Intake (TEI) was estimated through a single 24 h Recall Questionnaire, and urinary sodium and potassium excretion was estimated by a 24 h urine collection. The association of %BF and BMI with 24 h sodium excretion was estimated by a binary logistic regression adjusted for sex, age, physical activity, total energy intake, parental education, and 24 h urinary excreted potassium. There was a significant positive association between higher levels of urinary sodium excretion and higher %BF values, even after adjusting for confounders. However, the same was not observed for BMI. Our findings suggest that higher sodium intake is associated with higher values of %BF among children, regardless of TEI and potassium intake.

[Trauma Injuries Associated with Rope Bullfights in the Azores: A Cross-Sectional Study]. / Trauma Associado às Touradas à Corda nos Açores: Um Estudo Transversal.

INTRODUCTION: The aim of the study was to describe trauma injuries associated with rope bullfights in the Azores, Portugal, regarding the cause of the incident, trauma mechanism, most affected anatomical areas, and injury severity. METHODS: Two-year cross-sectional study in the local hospital with prospective data collection. Patients who were consecutively admitted to the local hospital's emergency department with trauma injuries from the bull's direct impact or from falls either during the bull's escape or when handling the rope, were included. Data on general demographics, lesion characteristics, treatments, need for hospitalization and mortality were collected. RESULTS: Fifty-six incidents and 80 trauma injuries were identified. The main cause of trauma was the bull's direct impact (37; 66.07%) and the mechanism of injury was blunt trauma in all patients (100%; 56). Head and neck injuries (27; 33.75%) were the most common. The median Injury Severity Score at the emergency department admission was 4. Major trauma was noted in five patients (8.92%). Ten patients (17.85%) needed hospitalization with a median hospital stay of seven days. Three of the 10 hospitalized patients (30%) were previously admitted to the intensive care unit. Surgery was performed in six patients (10.71%). CONCLUSION: The main cause of trauma was the bull's direct impact, and the mechanism of injury was blunt trauma. The most affected anatomical areas were the head and neck. These findings are a wake-up call to the impact of these events regarding the economic costs they entail, the costs for the health of the local population, the safety measures currently implemented and the availability of the necessary means to treat these patients.

Introdução: O objetivo deste estudo foi caracterizar as lesões traumáticas tauromáquicas ocorridas nas touradas à corda nos Açores no que diz respeito à causa do incidente, mecanismo de trauma, área anatómica mais afetada e gravidade das lesões. Métodos: Estudo unicêntrico, transversal, com a colheita prospetiva de dados realizada durante dois anos. Foram incluídos os doentes que consecutivamente recorreram ao serviço de urgência do hospital local por lesões traumáticas ocorridas por trauma direto com o animal ou quedas aquando da fuga ou manuseio da corda. Foram colhidos dados demográficos gerais, características da lesão, tratamentos efetuados, necessidade de internamento hospitalar e mortalidade. Foi realizada uma análise estatística descritiva com recurso ao software estatístico SPSS. Resultados: Registaram-se 56 admissões hospitalares e 80 lesões traumáticas. A principal causa de traumatismo foi o trauma direto com o animal (37; 66,07%) e o mecanismo de lesão foi o trauma fechado (56; 100%). As áreas anatómicas mais afetadas foram a cabeça e pescoço (27; 33,75%). A mediana de Injury Severity Score foi de 4 à admissão hospitalar. Cinco doentes (8,92%) apresentaram trauma major. Dez doentes (17,85%) necessitaram de internamento hospitalar com uma mediana de dias de internamento de sete (IIQ 4,5 dias). Três (30%) dos doentes internados necessitaram de internamento em unidade de cuidados intensivos. Seis doentes (10,71%) foram submetidos a cirurgia. Conclusão: A principal causa de traumatismo foi o trauma direto com o animal e o mecanismo de lesão foi o trauma fechado. As áreas anatómicas mais afetadas foram a cabeça e pescoço. Estes dados constituem um alerta para o impacto destes eventos no que diz respeito aos custos económicos que acarretam, aos custos para a saúde da população local, às medidas de segurança atualmente implementadas e à disponibilidade dos meios necessários para tratar estes doentes.

Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

Rare Combination of Chyloperitoneum Secondary to Primary Small-Bowel Volvulus.

Chylous ascites is the exudation from lymphatic content to the peritoneum and is a rare situation that mostly occurs following medical causes like neoplasms or cirrhosis. However, trauma to the lymphatic system due to compression by masses or altered anatomy can be a trigger too. We describe a rare combination of a primary small bowel volvulus in a young healthy adult causing chylous ascites. Obstruction caused by a primary small bowell volvulus can re-arrange the lymphatics anatomy increasing their flow pressure which can lead to rupture and leak. This is an emergent scenario that needs to be addressed quickly because of bowel ischaemia. CT scan is the gold standard to expedite diagnosis and go to surgical treatment. Although it can be an impactful finding, treatment of the cause behind chylous ascites results in complete resolution without any bowel resection.

O uso do laser de alta e baixa intensidade para o tratamento de hipersensibilidade dentinária: uma revisão integrativa

Objetivo: Determinar as evidências científicas sobre a influência do uso de lasers de baixa e alta intensidade no tratamento da hipersensibilidade da dentina. Revisão de literatura: Foram realizadas buscas na Biblioteca Virtual em Saúde (BVS), incluindo as bases de dados: Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS); Bibliografia Brasileira de Odontologia (BBO); e National Library of Medicine (MEDLINE). A maioria dos estudos destacam a eficácia dos lasers na redução da HD, com o laser Nd:YAG mostrando-se eficaz na obliteração dos túbulos dentinários e proporcionando alívio a longo prazo. Apesar dos benefícios, alguns estudos alertam para possíveis danos à polpa dentária, especialmente com lasers de alta potência. Considerações finais: Embora os lasers tenham se mostrado eficazes na redução da HD, a escolha do laser deve ser personalizada para cada paciente, destacando a necessidade de aprimorar os protocolos clínicos e adquirir experiência relevante por parte dos profissionais especialistas.

Objective: To determine the scientific evidence on the influence of the use of low and high intensity lasers in the treatment of dentin hypersensitivity. Literature review: Searches were carried out in the Virtual Health Library (VHL), including the databases: Latin American and Caribbean Literature in Health Sciences (LILACS); Brazilian Bibliography of Dentistry (BBO); and National Library of Medicine (MEDLINE). Most studies highlight the effectiveness of lasers in reducing HD, with the Nd:YAG laser proving effective in obliterating dentinal tubules and providing long-term relief. Despite the benefits, some studies warn of possible damage to the dental pulp, especially with high-power lasers. Final considerations: Although lasers have been shown to be effective in reducing HD, the choice of laser must be personalized for each patient, highlighting the need to improve clinical protocols and acquire relevant experience on the part of specialist professionals.

Electromyographic activity of pelvic floor muscles in different positions during the use an innovative vaginal educator: Cross-sectional study.

The pelvic floor requires an integrated anatomical structure owing to its multiple functions. Therefore, it is necessary to study methods for improving muscle recruitment during training. This study aimed to analyze the effect of using an innovative vaginal trainer on the bioelectrical activity of the pelvic floor muscles. Pelvic positioning and interference factors, such as age, childbirth, sexual activity, urinary incontinence, and menopause, were also analyzed. A cross-sectional study assessed 30 women using an evaluation form, International Consultation on Incontinence Questionnaire-Short Form, and surface electromyography. The root mean square of a 5-second contraction period, peak root mean square values, area values, % maximal voluntary contraction (root mean square normalized by peak signal), and median frequency were collected. These findings with and without the use of a vaginal educator were compared in the anteversion, neutral, and retroversion pelvic positions. The use of a vaginal educator was found to increase the electromyographic activity of the pelvic floor muscles in the neutral position. In this position, older women showed an increased peak contraction when using the educator. Multiparas also benefited from increased bioelectric activity (root mean square and area). Sexually active women increased their bioelectric activity in a neutral position when using the trainer, exerting less effort in retroversion (%-maximal voluntary contraction). Incontinent and menopausal women exhibited slower body-building activation (decreased frequency) with the device, which requires further investigation. Our innovative biofeedback device induced greater recruitment of muscle fibers, is more effective in the neutral pelvic position, and may be effective in training the pelvic floor muscles, even in women with a greater tendency toward pelvic floor dysfunction.

Effect of the COVID-19 pandemic on cataract surgery by residents who had routine surgical simulator training during residency.

PURPOSE: To assess the effect of the Coronavirus disease 2019 (COVID-19) pandemic on cataract surgery by residents who had mandatory surgical simulator training during residency. METHODS: In this retrospective, observational analytical study, the total number of cataract surgeries and surgical complications by all senior residents of 2019 (2019 class; prepandemic) and 2020 (2020 class; affected by the reduced number of elective surgeries due to the COVID-19 pandemic) were collected and compared. All residents had routine mandatory cataract surgery training on a virtual surgical simulator during residency. The total score obtained by these residents on cataract challenges of the surgical simulator was also evaluated. RESULTS: The 2020 and 2019 classes performed 1275 and 2561 cataract surgeries, respectively. This revealed a reduction of 50.2% in the total number of procedures performed by the 2020 class because of the pandemic. The incidence of surgical complications was not statistically different between the two groups (4.2% in the 2019 class and 4.9% in the 2020 class; p=0.314). Both groups also did not differ in their mean scores on the simulator's cataract challenges (p<0.696). CONCLUSION: Despite the reduction of 50.2% in the total number of cataract surgeries performed by senior residents of 2020 during the COVID-19 pandemic, the incidence of surgical complications did not increase. This suggests that surgical simulator training during residency mitigated the negative effects of the reduced surgical volume during the pandemic.

The Caenorhabditis elegans neuroendocrine system and their modulators: An overview.

In this review we seek to systematically bring what has been published in the literature about the nervous system, endocrine system, neuroendocrine relationships, neuroendocrine modulations and endocrine disruptors in the alternative model Caenorhabditis elegans. The serotonergic, dopaminergic, GABAergic and glutamatergic neurotransmitters are related to the modulation of the neuroendocrine axis, leading to the activation or inhibition of several processes that occur in the worm through distinct and interconnected pathways. Furthermore, this review addresses the gut-neuronal axis as it has been revealed in recent years that gut microbiota impacts on neuronal functions. This review also approaches xenobiotics that can positively or negatively impact the neuroendocrine system in C. elegans as in mammals, which allows the application of this nematode to screen new drugs and to identify toxicants that are endocrine disruptors.

Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates.

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

Why are pregnant women physically inactive? A qualitative study on the beliefs and perceptions about physical activity during pregnancy.

This study aimed to describe the beliefs and perceptions of pregnant women and healthcare providers about physical activity during pregnancy. Using a qualitative approach, 30 pregnant women and the 14 healthcare providers caring for them were interviewed in the second trimester of pregnancy. We included women who maintained, decreased, or stopped physical activity since becoming pregnant. They were divided into low (≤ 8 years) and high schooling (> 8 years). Semi-structured, in-depth interviews were conducted and guided by three key questions: (1) When does physical activity during pregnancy start to be considered a wrong behavior?; (2) What are the main barriers (biological or others) to physical activity?; and (3) Do the actions of healthcare providers and people close to pregnant women reinforce barriers? Interviews were audio recorded, transcribed, and analyzed based on recurring themes. All women changed their physical activity behavior (decreased or stopped) when they discovered their pregnancy. Fear of miscarriage, contractions, bleeding, and of causing malformations in the baby were the most reported reasons for decreasing or stopping physical activity. Participants also lacked access to consistent information and healthcare providers' support on the benefits of physical activity. Despite the current international recommendations to regular physical activity during pregnancy, uncertainty regarding its benefits remains. Interventions to promote physical activity during this period should include the training of healthcare providers so they can advise and discard ideas contrary to mother-child health benefits.

Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes.

BACKGROUND: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear. METHODS: We explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women. RESULTS: All three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation. CONCLUSIONS: Our findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications. FUNDING: Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Effect of the COVID-19 pandemic on cataract surgery by residents who had routine surgical simulator training during residency

ABSTRACT Purpose: To assess the effect of the coronavirus disease 2019 (COVID-19) pandemic on cataract surgery by residents who had mandatory surgical simulator training during residency. Methods: In this retrospective, observational analytical study, the total number of cataract surgeries and surgical complications by all senior residents of 2019 (2019 class; prepandemic) and 2020 (2020 class; affected by the reduced number of elective surgeries due to the COVID-19 pandemic) were collected and compared. All residents had routine mandatory cataract surgery training on a virtual surgical simulator during residency. The total score obtained by these residents on cataract challenges of the surgical simulator was also evaluated. Results: The 2020 and 2019 classes performed 1275 and 2561 cataract surgeries, respectively. This revealed a reduction of 50.2% in the total number of procedures performed by the 2020 class because of the pandemic. The incidence of surgical complications was not statistically different between the two groups (4.2% in the 2019 class and 4.9% in the 2020 class; p=0.314). Both groups also did not differ in their mean scores on the simulator's cataract challenges (p<0.696). Conclusion: Despite the reduction of 50.2% in the total number of cataract surgeries performed by senior residents of 2020 during the COVID-19 pandemic, the incidence of surgical complications did not increase. This suggests that surgical simulator training during residency mitigated the negative effects of the reduced surgical volume during the pandemic.