Assessment of oxidative stress biomarkers in the threatened annual killifish Austrolebias charrua exposed to Roundup.

This study aimed to analyze the toxic effects of Roundup Transorb® on the endangered Neotropical annual killifish Austrolebias charrua through the assessment of molecular and biochemical biomarkers. The fish were collected in temporary ponds and exposed to environmentally realistic concentrations of the herbicide (5 mg.L-1 for 96 h). The production of ROS, lipid peroxidation, DNA damage, and membrane fluidity were evaluated in the blood cells by flow cytometry. The mRNA expression of the antioxidant-related genes sod2, cat, gstα, atp1a1, gclc, and ucp1 across the brain, liver, and gills was quantified. The acute exposure of annual killifish to Roundup significantly increased ROS production, lipid peroxidation, and DNA damage in their erythrocytes. Likewise, Roundup Transorb® decreased membrane fluidity in the blood cells of the exposed fish. Gene expression analysis revealed that Roundup exposure alters the relative expression of genes associated with oxidative stress and antioxidant defense. Our results give rise to new insights into adaptive mechanisms of A. charrua in response to Roundup. Since Brazilian annual killifishes strongly risk extinction, this study paves the way for developing novel biotechnologies applied to environmental monitoring and aquatic toxicology assessment.

Resultados além do gerenciamento da infecção em um serviço de Gerenciamento da Terapia Medicamentos para pessoas vivendo com HIV

Avaliar os resultados clínicos de serviços de gerenciamento da terapia medicamentosa (GTM) oferecidos a pessoas vivendo com HIV (PVHIV) em uma unidade de dispensação de medicamentos brasileira. O estudo foi dividido em uma etapa transversal (etapa I), que avaliou o fator associado à identificação de dois ou mais problemas relacionados ao uso de medicamentos (PRM) na avaliação inicial; e uma etapa quasi- experimental (etapa II), realizada com um único grupo de pacientes para avaliar desfechos clínicosForam acompanhadas 52 PVHIV. A média de idade foi de 60±11,3 anos (min. = 29; máx. =78). A presença de dislipidemia (OR=5,38; IC 95%=1,61-17,97; p=0,006) e o uso de sete ou mais medicamentos (OR=4,28; IC 95%=1,32-13,88; p=0,015) foram fatores associados a identificação de dois ou mais PRM. Foi demonstrada uma diferença significativa entre os valores iniciais e finais de pressão arterial sistólica, carga viral do HIV, contagem de células T CD4+ e triglicerídeos (p<0,05). O serviço de GTM favoreceu os desfechos clínicos positivos.

To assess the clinical outcomes of comprehensive medication management (CMM) services offered to people living with HIV (PLHIV) at a Brazilian Antiretroviral Medication Dispensing Unit. The study was divided into a cross-sectional stage (stage I), to evaluate associated factor with the identification of two or more drug therapy problems (DTP) in the initial assessment; and a quasi-experimental stage (stage II), conducted with a single group of PLHIV to evaluate clinical outcomes. A total of 52 PLHIV, with 60±11.3 years of age were followed up. In stage I, the presence of dyslipidemia (OR=5.38; 95%CI=1.61-17.97) and the use of seven or more medications (OR=4.28; 95% CI=1.32-13.88) were factors associated with the identification of DTP. In stage II, a significant difference was demonstrated between the initial and final values of systolic blood pressure, triglycerides, HIV viral load and CD4+T-cells count (p<0,05). The CMM service favored positive clinical outcomes.

Potential Therapeutic Targets of Quercetin in the Cutaneous Melanoma Model and Its Cellular Regulation Pathways: A Systematic Review.

Melanoma is a skin cancer with a high mortality rate due to its invasive characteristics. Currently, immunotherapy and targeted therapy increase patient survival but are ineffective in the advanced stages of the tumor. Quercetin (Que) is a natural compound that has demonstrated chemopreventive effects against different types of tumors. This review provides evidence for the therapeutic potential of Que in melanoma and identifies its main targets. The Scopus, Web of Science, and PubMed databases were searched, and studies that used free or encapsulated Que in melanoma models were included, excluding associations, analogs, and extracts. As a result, 73 articles were retrieved and their data extracted. Que has multiple cellular targets in melanoma models, and the main regulated pathways are cell death, redox metabolism, metastasis, and melanization. Que was also able to regulate important targets of signaling pathways, such as PKC, RIG-I, STAT, and P53. In murine models, treatment with Que reduced tumor growth and weight, and decreased metastatic nodules and angiogenic vasculature. Several studies have incorporated Que into carriers, demonstrating improved efficacy and delivery to tumors. Thus, Que is a promising therapeutic agent for the treatment of melanoma; however, further studies are needed to evaluate its effectiveness in clinical trials.

The Correlation between Anthropometric Variables and Muscular Strength in Patients Coinfected with Leprosy and HIV.

Background: Peripheral nerve disease may lead to physical disability because of decreased muscle strength and/or loss of sensitivity in the dermatomes of affected peripheral nerves. Both human immunodeficiency virus (HIV)- and leprosy-affected patients can develop neurological damage; therefore, the coinfection of these diseases presents new challenges to the health care of these patients. Aims and Objective: This study aimed to investigate the motor alterations of patients coinfected with HIV and leprosy and their relationship with clinical and anthropometric characteristics, compared with individuals with isolated diseases. Materials and Methods: In this cross-sectional study, 90 individuals were divided equally into three groups: HIV/acquired immunodeficiency syndrome (AIDS) group, leprosy group and HIV/leprosy group. All individuals underwent an evaluation of muscle strength and upper limb endurance adjusted for the Brazilian standards, a palm print pressure test using a digital dynamometer and anthropometric measurements (weight, height and skin folds). Results: The HIV/leprosy group had the highest mean body mass index, followed by the leprosy group and the HIV/AIDS group. Skinfolds were similar between the groups. Multiple linear regression, adjusted for sex and age, revealed the coinfection of HIV and leprosy as possible contributor to a worse prognosis of muscle function, highlighting the bilateral reduction in the levels of palm print compression strengths compared with isolated diseases (HIV and leprosy). High CD4 count and shorter antiretroviral therapy duration were associated with worse indices of muscle strength, such as gripping and resistance, in coinfected patients. Conclusion: Patients coinfected with HIV and leprosy exhibited greater motor damage than those with isolated diseases. Thus, motor damage may be related to the sum of the neurological manifestations of the two morbidities.

A non-transmissible live attenuated SARS-CoV-2 vaccine.

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.

Genome sequencing of Cladophialophora exuberans, a novel candidate for bioremediation of hydrocarbon and heavy metal polluted habitats.

Cladophialophora exuberans is a filamentous fungus related to black yeasts in the order Chaetothyriales. These melanized fungi are known for their 'dual ecology', often occurring in toxic environments and also being frequently involved in human infection. Particularly Cladophialophora exuberans, C. immunda, C. psammophila, and Exophiala mesophila have been described with a pronounced ability to degrade aromatic compounds and xenobiotic volatiles, such as benzene, toluene, ethyl-benzene, and xylene, and are candidates for bioremediation applications. The objective of the present study is the sequencing, assembly, and description of the whole genome of C. exuberans focusing on genes and pathways related to carbon and toxin management, assessing the tolerance and bioremediation of lead and copper, and verifying the presence of genes for metal homeostasis. Genomic evaluations were carried out through a comparison with sibling species including clinical and environmental strains. Tolerance of metals was evaluated via a microdilution method establishing minimum inhibitory (MIC) and fungicidal concentrations (MFC), and agar diffusion assays. Heavy metal bioremediation was evaluated via graphite furnace atomic absorption spectroscopy (GFAAS). The final assembly of C. exuberans comprised 661 contigs, with genome size of 38.10 Mb, coverage of 89.9X and a GC content of 50.8%. In addition, inhibition of growth was shown at concentrations of 1250 ppm for copper and at 625 ppm for lead, using the MIC method. In the agar tests, the strain grew at 2500 ppm of copper and lead. In GFAAS tests, uptake capacities were observed of 89.2% and 95.7% for copper and lead, respectively, after 21 experimental days. This study enabled the annotation of genes involved in heavy metal homeostasis and also contributed to a better understanding of the mechanisms used in tolerance of and adaptation to extreme conditions.

Diet supplemented with Saccharomyces cerevisiae from different fermentation media modulates the faecal microbiota and the intestinal fermentative products in dogs.

This study aimed at evaluating the coefficients of total tract apparent digestibility (CTTAD) of nutrients, metabolisable energy (ME), diet palatability, faecal fermentative products and microbiota of dogs fed yeasts from different fermentation media and its fractions. Four diets were evaluated: control, without yeast (CO); diet with 10 g/kg brewer's yeast (BY); diet with 10 g/kg brewer's yeast + corn yeast (BCY); and diet with 10 g/kg BCY + cell wall fractions (BCYF). Twelve adult dogs were distributed in a randomized block design (periods). Each of the four diets was fed to a group of three dogs per period of 20 days, totalling two periods and six repetitions per treatment. Sixteen adult dogs were used for the palatability test, which compared the CO diet versus each one of the yeast diets. Data with normal distribution were subjected to analysis of variance (p < 0.05). Means were compared by orthogonal contrasts (p < 0.05): (A) CO diet versus BY, BCY and BCYF diets; (B) BY diet versus BCY and BCYF diets; (C) BCY diet versus BCYF diet. There was no difference in the CTTAD and ME of the diets (p > 0.05). Yeast diets reduced faecal odour and indole peak area (p < 0.05). Faecal short-chain fatty acids concentration was greater in dogs fed yeast diets compared to those fed the CO (p < 0.05). Yeast diets showed a higher intake ratio compared to the CO (p < 0.05). The BCY and BCYF diets resulted in a greater abundance of Bacteroides, Faecalibacterium, Coprococcus, and Phascolarctobacterium in relation to the CO (p < 0.05). Our results suggest that dietary yeast supplementation results in beneficial changes in intestinal functionality indicators, mainly with the combination of yeasts from brewers and corn fermentation media. In addition, yeast supplementation improves diet palatability without compromising nutrient digestibility.

Development and content validation of the medication literacy test for older adults (TELUMI).

OBJECTIVES: Medication literacy comprises the skills needed to access, understand, and act on medication information. Low medication literacy is frequent among older adults, making them more susceptible to negative health outcomes. The aim of this study was to develop and evaluate the content validity of an instrument to measure medication literacy in this population. METHOD: Multistage methodological study. Items were generated according to a conceptual model and a literature review. The instrument was submitted to a panel of experts to assess item's relevance, clarity, and theoretical classification. Subsequently, the instrument was applied to the target population to assess its comprehensibility. RESULTS: Content Validity Index results indicated excellent agreement among experts on the instrument's relevance (0.98) and clarity (0.91). Overall agreement between experts regarding the theoretical subdimensions was moderate [Fleiss' kappa=0.57 (p = 0.00)]. Items were reported to be fully understood by most representatives of the target population. The final version of the instrument had 33 items divided into eight scenarios of medication use. CONCLUSION: The instrument seems to have adequate content validity and good suitability for the target population. Therefore, it can help health professionals to identify older adults with low medication literacy, aiming to improve their medication use skills.

Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake.

BACKGROUND: Dietary sodium is a well-known risk factor for cardiovascular and renal disease; however, direct evidence of the longitudinal changes that occur with aging, and the influence of dietary sodium on the age-associated alterations are scarce. METHODS: C57BL/6 mice were maintained for 13 months on a low (LS, 0.02 % Na+), normal (NS, 0.3 % Na+) or high (HS, 1.6 % Na+) salt diet. We assessed 1) the longitudinal trajectories for two markers of cardiovascular and renal dysfunction (blood pressure (BP) and albuminuria), as well as hormonal changes, and 2) end-of-study cardiac and renal parameters. RESULTS: The effect of aging on BP and kidney damage did not reach significance levels in the LS group; however, relative to baseline, there were significant increases in these parameters for animals maintained on NS and HS diets, starting as early as month 7 and month 5, respectively. Furthermore, changes in albuminuria preceded the changes in BP relative to baseline, irrespective of the diet. Circulating aldosterone and plasma renin activity displayed the expected decreasing trends with age and dietary sodium loading. As compared to LS - higher dietary sodium consumption associated with increasing trends in left ventricular mass and volume indices, consistent with an eccentric dilated phenotype. Functional and molecular markers of kidney dysfunction displayed similar trends with increasing long-term sodium levels: higher renovascular resistance, increased glomerular volumes, as well as higher levels of renal angiotensin II type 1 and mineralocorticoid receptors, and lower renal Klotho levels. CONCLUSION: Our study provides a timeline for the development of cardiorenal dysfunction with aging, and documents that increasing dietary salt accelerates the age-induced phenotypes. In addition, we propose albuminuria as a prognostic biomarker for the future development of hypertension. Last, we identified functional and molecular markers of renal dysfunction that associate with long-term dietary salt loading.

Pet Rats as the Likely Reservoir for Human Seoul Orthohantavirus Infection.

Seoul orthohantavirus (SEOV) is a rat-associated zoonotic pathogen with an almost worldwide distribution. In 2019, the first autochthonous human case of SEOV-induced hemorrhagic fever with renal syndrome was reported in Germany, and a pet rat was identified as the source of the zoonotic infection. To further investigate the SEOV reservoir, additional rats from the patient and another owner, all of which were purchased from the same vendor, were tested. SEOV RNA and anti-SEOV antibodies were found in both of the patient's rats and in two of the three rats belonging to the other owner. The complete coding sequences of the small (S), medium (M), and large (L) segments obtained from one rat per owner exhibited a high sequence similarity to SEOV strains of breeder rat or human origin from the Netherlands, France, the USA, and Great Britain. Serological screening of 490 rats from breeding facilities and 563 wild rats from Germany (2007-2020) as well as 594 wild rats from the Netherlands (2013-2021) revealed 1 and 6 seropositive individuals, respectively. However, SEOV RNA was not detected in any of these animals. Increased surveillance of pet, breeder, and wild rats is needed to identify the origin of the SEOV strain in Europe and to develop measures to prevent transmission to the human population.

Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats.

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3ß (GSK3ß) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3ß, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3ß protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3ß and possibly associated with a decrease in muscle injury.

Suicidal Phenotype of Proofreading-Deficient Herpes Simplex Virus 1 Polymerase Mutants.

Herpes simplex virus 1 (HSV-1) encodes a family B DNA polymerase (Pol) capable of exonucleolytic proofreading whose functions have been extensively studied in the past. Early studies on the in vitro activity of purified Pol protein found that the enzymatic functions of the holoenzyme are largely separate. Consequently, exonuclease activity can be reduced or abolished by certain point mutations within catalytically important regions, with no or only minor effects on polymerase activity. Despite unimpaired polymerase activity, the recovery of HSV-1 mutants with a catalytically inactive exonuclease has been so far unsuccessful. Hence, mutations such as D368A, which abolish exonuclease activity, are believed to be lethal. Here, we show that HSV-1 can be recovered in the absence of Pol intrinsic exonuclease activity and demonstrate that a lack of proofreading causes the rapid accumulation of likely detrimental mutations. Although mutations that abolish exonuclease activity do not appear to be lethal, the lack of proofreading yields viruses with a suicidal phenotype that cease to replicate within few passages following reconstitution. Hence, we conclude that high replication fidelity conferred by proofreading is essential to maintain HSV-1 genome integrity and that a lack of exonuclease activity produces an initially viable but rapidly suicidal phenotype. However, stably replicating viruses with reduced exonuclease activity and therefore elevated mutation rates can be generated by mutating a catalytically less important site located within a conserved exonuclease domain. IMPORTANCE Recovery of fully exonuclease-deficient herpes simplex virus 1 (HSV-1) DNA polymerase mutants has been so far unsuccessful. However, exonuclease activity is not known to be directly essential for virus replication, and the lethal phenotype of certain HSV-1 polymerase mutants is thus attributed to factors other than exonuclease activity. Here, we showed that the recovery of a variety of exonuclease-deficient HSV-1 polymerase mutants is possible and that these mutants are initially replication competent. We, however, observed a progressive loss of mutant viability upon cell culture passaging, which coincided with the rapid accumulation of mutations in exonuclease-deficient viruses. We thus concluded that a lack of DNA proofreading in exonuclease-deficient viruses causes an initially viable but rapidly suicidal hypermutator phenotype and, consequently, the extinction of mutant viruses within few generations following recovery. This would make the absence of exonuclease activity the primary reason for the long-reported difficulties in culturing exonuclease-deficient HSV-1 mutants.

Telemonitoramento de idosos usuários de anticoagulante durante a pandemia da COVID-19 / Telemonitoring of older anticoagulant users during the COVID-19 pandemic

A pandemia da COVID-19 trouxe desafios para o monitoramento de usuários de anticoagulantes, sobretudo idosos, sendo o telemonitoramento uma alternativa para dar continuidade aos cuidados para esses pacientes. O presente estudo teve como objetivo descrever a experiência do telemonitoramento de idosos usuários de anticoagulantes na pandemia da COVID-19. Trata-se de estudo referente ao serviço farmacêutico de telemonitoramento de idosos (≥60 anos) em uso de anticoagulantes orais em ambulatório de geriatria privado (Belo Horizonte). Idosos tiveram parâmetros de efetividade e segurança dos anticoagulantes monitorados mensalmente por telefone (abr-dez/2021). Problemas identificados geraram intervenções ao paciente ou equipe multiprofissional. Ao total 425 idosos foram incluídos no serviço. A maioria usava apixabana (189;41,9%), rivaroxabana (146;34,4%) e varfarina (47;11,1%). Observou-se média de idade de 82,1 anos, maioria feminina (65,2%), maioria com alto risco de vulnerabilidade (69%), e incidência de 9,9% de COVID-19. Realizou-se 219 intervenções relativas à varfarina (média de 4,6 intervenções/paciente); referiram-se à solicitação de exame de RNI (57,5%), orientações em saúde (19,6%), alteração da dose (redução - 10,5%; aumento - 5,9%; suspensão - 0,6%), ou encaminhamento (5,9%). Usuários de outros anticoagulantes não apresentaram alterações nos parâmetros acompanhados. Onze idosos sofreram quedas e 10 demandaram internação por eventos tromboembólicos ou hemorrágicos. Não houve diferença estatisticamente significativa nas proporções de internação entre usuários de varfarina ou outros anticoagulantes (p=0,314). Acompanhar idosos usuários de anticoagulantes é importante, sobretudo considerando-se o alto nível de fragilidade identificado e os riscos tromboembólicos e não-tromboembólicos que a COVID-19 traz. O telemonitoramento foi importante, permitindo realização de múltiplas intervenções.

The COVID-19 pandemic brought challenges to the monitoring of anticoagulant users, especially older adults, making telemonitoring an alternative to provide continuity of care for these patients. The present study aimed to describe the experience of telemonitoring of older anticoagulant users during the COVID-19 pandemic. This is a descriptive study concerning the telemonitoring pharmaceutical service for older adults (≥60 years old) using oral anticoagulants in a private geriatric outpatient clinic (Belo Horizonte). Older people had parameters of effectiveness and safety of anticoagulants monitored monthly by telephone (Apr-Dec/2021). Identified problems generated interventions for the patient or the multidisciplinary team. A total of 425 older adults were included in the service. Most used apixaban (189;41.9%), rivaroxaban (146;34.4%) and warfarin (47;11.1%). There was a mean age of 82.1 years, mostly female (65.2%), most at high risk of vulnerability (69%), and an incidence of 9.9% of COVID-19. There were 219 interventions related to warfarin (average of 4.6 interventions/patient); including requests for an INR test (57.5%), health guidelines (19.6%), dosage change (reduction - 10.5%; increase - 5.9%; suspension - 0.6%), or referral (5.9%). Users of other anticoagulants did not show alterations in the monitored parameters. Eleven older adults suffered falls and 10 required hospitalizations due to thromboembolic or hemorrhagic events. There was no statistically significant difference in hospitalization rates between users of warfarin or other anticoagulants (p=0.314). Monitoring older anticoagulant users is important, especially considering the high level of frailty identified and the thromboembolic and non-thromboembolic risks that COVID-19 brings. Telemonitoring was important, allowing for multiple interventions to be performed.

As múltiplas violências vivenciadas por farmacêuticas no ambiente laboral / The multiple violences experienced by pharmacist women in the workplace / Las múltiples violencias experimentadas por las farmacéuticas en el entorno laboral

Resumo A divisão sexual do trabalho ocasiona iniquidade entre gêneros, bem como situações de violência direcionadas às mulheres no ambiente laboral. Na área farmacêutica, a maioria feminina e a inserção em múltiplos cenários, que envolvem contato com público e parcerias profissionais diferenciadas, potencializam a exposição à violência. Assim, o objetivo deste estudo foi analisar situações de violência vivenciadas por farmacêuticas no ambiente laboral. Para tal, utilizou-se método qualitativo, com análise de conteúdo, realizada no software NVivo®, de uma survey on line, respondida por farmacêuticas (n=381) registradas no Conselho Regional de Farmácia de Minas Gerais, Brasil. Como resultado, identificou-se quatro categorias: 'Convivendo com o desrespeito, ameaças e vulnerabilidade', 'O sexismo e o machismo estrutural que cala, diminui e atordoa', 'A discriminação contra a mulher como obstáculo à equidade' e 'Assédio sexual e objetificação da mulher'. Emergiram diversas expressões de violências no ambiente laboral provenientes de múltiplos agressores. Farmacêuticas reconheceram prejuízo profissional e pouco reconhecimento pela capacidade técnica. Conclui-se que os relatos expuseram a falta de proteção da integridade farmacêutica no ambiente de trabalho. Espera-se que esses resultados tragam à luz a desigualdade de gênero no trabalho farmacêutico, com destaque para situações de violência, ampliando a discussão e proporcionando evolução dessa profissão majoritariamente feminina.

Abstract The sexual division of labor causes inequality between genders, as well as situations of violence directed to women in the workplace. In the pharmaceutical area, the majority of women and insertion in multiple scenarios, involving contact with public and differentiated professional partnerships, enhance exposure to violence. Thus, the objective of this study was to analyze situations of violence experienced by pharmacists in the workplace. For this, a qualitative method was used, with content analysis, performed in the NVivo® software, of an online survey, answered by pharmacists (n=381) registered in the Regional Pharmacy Council of Minas Gerais, Brazil. As a result, four categories were identified: 'Living with disrespect, threats and vulnerability,' 'Sexism and structural chauvinism that shuts down, diminishes and torments,' 'Discrimination against women as an obstacle to equity' and 'Sexual harassment and objectification of women.' Several expressions of violence in the labor environment emerged from multiple aggressors. Pharmacists recognized professional impairment and little recognition for technical capacity. We concluded that the reports exposed the lack of protection of pharmaceutical integrity in the workplace. It is expected that these results bring to light the gender inequality in pharmaceutical work, with emphasis on situations of violence, expanding the discussion and providing evolution of this mostly female profession.

Resumen La división sexual del trabajo ocasiona iniquidad entre los géneros, así como situaciones de violencia dirigidas a las mujeres en el entorno laboral. En el ámbito farmacéutico, la mayoría de las mujeres y la inserción en múltiples escenarios, que implican contacto con el público y asociaciones profesionales diferenciadas, potencian la exposición a la violencia. Por lo tanto, el objetivo de este estudio fue analizar las situaciones de violencia experimentadas por las farmacéuticas en el entorno laboral. Para esto, se utilizó un método cualitativo, con análisis de contenido, realizado en el software NVivo®, de una encuesta en línea, respondida por farmacéuticas (n=381) registradas en el Consejo Regional de Farmacia de Minas Gerais, Brasil. A consecuencia, se identificaron cuatro categorías: 'Conviviendo con falta de respeto, amenazas y vulnerabilidad', 'el sexismo y el machismo estructural que cala, disminuye y atormentó', 'la discriminación contra la mujer como obstáculo a la equidad' y 'el acoso sexual y la objeción de la mujer'. Han surgido varias expresiones de violencia en el entorno laboral procedentes de múltiples agresores. Los productos farmacéuticos han reconocido el daño profesional y el escaso reconocimiento de la capacidad técnica. Se concluye que los informes haciendo hincapié de manifiesto la falta de protección de la integridad farmacéutica en el entorno laboral. Se espera que estos resultados traigan a la luz la desigualdad de género en el trabajo farmacéutico, haciendo hincapié en las situaciones de violencia, ampliando el debate y dando lugar a la evolución de esa profesión principalmente femenina.

Sedative use and incidence of falls and hip fractures among older adults in an outpatient geriatric clinic / Perfil de uso de sedativos e ocorrência de quedas e fratura de fêmur entre idosos em um ambulatório de geriatria

OBJECTIVE: To investigate the use of sedatives by older adults attending a private outpatient geriatric clinic in Belo Horizonte (MG), Brazil, and its association with falls and hip fractures. METHODS: Using a longitudinal design, the prevalence of benzodiazepine and nonbenzodiazepine ("z-drugs") intake by older adults was described and their association with the incidence of falls and fractures (30 days after the initial visit) was evaluated through logistic regression. RESULTS: A total of 7821 older adults were included in the study, most of them women (72.50%), with a mean age of 77.5 years and a mean Clinical-Functional Vulnerability Index (IVCF-20) score of 16.5. The overall prevalence of sedative use (any sedative) was 6.19%, with 4.48% benzodiazepines and 1.98% z-drugs. The most widely used sedatives were clonazepam (29.04%), zolpidem (28.65%), and alprazolam (23.44%). Falls were reported for 182 patients (2.33%), with a higher incidence among users of any sedatives (4.34; p = 0.002; OR = 1.94, adjusted for sex, age, and IVCF-20) and benzodiazepines (5.14%; p < 0.001; OR = 2.28) than among non-users (2.19%). Hip fractures occurred in 33 patients (0.42%), and again were more frequent among users of sedatives (1.03%; p = 0.032; OR = 2.57) and benzodiazepines (1.43%; p = 0.003; OR = 3.45) than among non-users (0.38%). CONCLUSIONS: The use of sedatives, especially benzodiazepines, is associated with an increased incidence of falls and hip fractures in older adults

OBJETIVO: Investigar a utilização de sedativos entre idosos atendidos em ambulatório privado de geriatria em Belo Horizonte (MG), bem como sua associação com quedas e fraturas de fêmur. METODOLOGIA: Trata-se de estudo longitudinal, no qual foi descrita a prevalência de uso de benzodiazepínicos e drogas Z entre idosos (60 anos ou mais) e avaliada sua associação com a incidência de queda e fratura (30 dias após consulta inicial) por meio de regressão logística. RESULTADOS: Foram incluídos no estudo 7821 idosos, com maioria feminina (72,50%), idade média de 77,5 anos e Índice de Vulnerabilidade Clínico Funcional (IVCF-20) médio de 16,5 pontos. A prevalência de uso de sedativos em geral foi de 6,19%, sendo 4,48% de benzodiazepínicos e 1,98% de drogas Z. Os medicamentos sedativos mais utilizados foram clonazepam (29,04%), zolpidem (28,65%) e alprazolam (23,44%). Relatou-se queda para 182 idosos (2,33%), com incidência maior entre usuários de sedativos (4,34; p = 0,002; OR = 1,94 ajustada por sexo, idade e IVCF-20) e de benzodiazepínicos (5,14%; p < 0,001; OR = 2,28) do que entre não usuários (2,19%). Identificou-se fratura de fêmur em 33 idosos (0,42%), sendo mais frequente entre usuários de sedativos (1,03%; p = 0,032; OR = 2,57) e de benzodiazepínicos (1,43%; p = 0,003; OR = 3,45) do que entre não usuários (0,38%). CONCLUSÃO: Concluiu-se que a incidência de quedas e fraturas de fêmur em idosos possui associação com o uso de medicamentos sedativos, em especial os benzodiazepínicos

The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury.

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor ß and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.

Key brain cell interactions and contributions to the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, with the two major hallmarks being the deposition of extracellular ß-amyloid (Aß) plaques and of intracellular neurofibrillary tangles (NFTs). Additionally, early pathological events such as cerebrovascular alterations, a compromised blood-brain barrier (BBB) integrity, neuroinflammation and synaptic dysfunction, culminate in neuron loss and cognitive deficits. AD symptoms reflect a loss of neuronal circuit integrity in the brain; however, neurons do not operate in isolation. An exclusively neurocentric approach is insufficient to understand this disease, and the contribution of other brain cells including astrocytes, microglia, and vascular cells must be integrated in the context. The delicate balance of interactions between these cells, required for healthy brain function, is disrupted during disease. To design successful therapies, it is critical to understand the complex brain cellular connections in AD and the temporal sequence of their disturbance. In this review, we discuss the interactions between different brain cells, from physiological conditions to their pathological reactions in AD, and how this basic knowledge can be crucial for developing new therapeutic strategies.

Instruments to Measure Patient Satisfaction with Comprehensive Medication Management Services: A Scoping Review Protocol.

Comprehensive medication management (CMM) is the service offered within the clinical practice of pharmaceutical care, which has the objective to optimize pharmacotherapeutic outcomes. Patient satisfaction is a multidimensional construct that points to the quality of the health services offered and the degree to which the patients' expectations and needs are met. The evaluation of the level of patient satisfaction is a key indicator to support decisions and to improve the quality of the service provided. This study aims to describe the protocol for a scoping review to map the instruments to measure patient satisfaction with CMM services and compare them according to their development characteristics and the applicability of patient-reported outcome measures. The literature search will be conducted using the scoping review methodology, proposed by the Joanna Briggs Institute and the PRISMA Extension for Scoping Reviews (PRISMA-ScR) method. The results will be presented in two sessions: (1) description of the search strategy; and (2) the characteristics of the satisfaction instruments, number of items and questions related to the conceptual model, content validity, construct validity, reliability, score/interpretation, and respondent burden. This review will shed light on the available satisfaction measurement instruments, allowing existing gaps to be identified for future research.

Use of psychotropic drugs by population in an area affected by the tailings dam rupture: Brumadinho Health Project.

OBJECTIVE: To describe the consumption of psychotropic drugs in the adult population residing in Brumadinho, Minas Gerais, after the Vale dam collapse, which occurred in 2019. METHODS: This is a cross-sectional study, part of the Brumadinho Health Project, developed in 2021, with a representative population-based sample of adults (18 years and over) residing in Brumadinho. A total of 2,805 adults with information on self-reported use of psychotropic drugs (antidepressants and anxiolytics-hypnotics/sedatives) in the last 15 days were included in the analysis. The prevalence of psychotropic drug use was estimated, and the most used psychotropic drugs were identified. Pearson's chi-square test (with Rao-Scott correction) was used to test associations between exposures and use of psychotropic drugs, considering a significance level of p<0.05. RESULTS: The use of antidepressants (14.2%) was more common than the use of anxiolytics or hypnotics/sedatives (5.2%), with sertraline and fluoxetine being the most used antidepressants. The use of anxiolytics and hypnotics/sedatives was higher among residents who lived in the area directly affected by the dam's mud, and the use of any psychotropic drug was higher among those who lost a relative/friend in the disaster and assessed that their health worsened after the disaster, and among women. CONCLUSION: The results of the study corroborate what was observed in other populations exposed to similar tragedies, regarding the pattern of associations and the of use of psychotropic drugs.