Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months.

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Health care itineraries for women in situations of abortion: methodological aspects of a qualitative study for Birth in Brazil II survey. / Itinerários de cuidado à saúde de mulheres em situações de abortamento: aspectos metodológicos do estudo qualitativo da pesquisa Nascer no Brasil II.

In recent decades, several academic studies on abortion have been produced in Brazil, with different designs, objectives, and methodologies. However, due to the diversity of situations in which Brazilian women experience abortion, the complexity of this topic, and its modulations in different political and sociocultural contexts, it still challenges academicians and the fields of health and reproductive rights. In this article, we present methodological aspects of a qualitative study on health care itineraries of women in situations of abortion, a component of the Birth in Brazil II survey, whose objective is to discuss the effects of gender; race/ethnicity; social class; generational, regional, and territorial inequalities on care itineraries. We discuss the study design development, the construction of the theoretical framework and specific analytical axes, the development of interview instrument, definition of participant selection criteria, strategies to contact participants and conduct the interviews, management of field work and materials produced, analytical procedures, and ethical issues. In total, 120 narrative interviews were conducted in order to include a diversity of women and obtain detailed results from the quantitative analysis under Birth in Brazil II survey. The context of criminalization of abortion has an impact on the production of knowledge on this subject, creating challenges such as difficult access to women, women's anonymity, privacy and data confidentiality, creation of objective and subjective conditions so that they can narrate their experiences in depth. With this article, we seek to contribute to the debate about these challenges in abortion research in Brazil.

Nas últimas décadas, produziu-se um robusto corpus de pesquisas sobre aborto no Brasil, com diferentes desenhos, objetos e metodologias. Contudo, pela diversidade de situações em que as mulheres brasileiras vivenciam o abortamento, pela complexidade do tema e por suas modulações em contextos políticos e socioculturais distintos, o assunto não cessa de desafiar a academia, o campo da saúde e dos direitos reprodutivos. Neste artigo, apresentamos aspectos metodológicos de um estudo qualitativo sobre itinerários de cuidado à saúde de mulheres em situações de abortamento, componente da pesquisa Nascer no Brasil II, que objetiva discutir efeitos das desigualdades de gênero, de raça/etnia, de classe social, geracionais, regionais e territoriais nesses percursos. Discutimos o desenvolvimento do desenho do estudo; a construção do arcabouço teórico e recortes analíticos específicos; a elaboração do instrumento de entrevista; os critérios de seleção das mulheres; as estratégias de abordagem e condução das entrevistas; a gestão do fluxo do campo e dos materiais produzidos; os procedimentos analíticos; e os problemas éticos. Para incluir uma diversidade de mulheres e aprofundar resultados do componente quantitativo do Nascer no Brasil II, serão realizadas 120 entrevistas narrativas. O contexto de criminalização do aborto impacta a produção de conhecimento sobre o tema, impondo desafios como conseguir acesso às mulheres, assegurar o anonimato e sua privacidade, além do sigilo das informações, gerar condições objetivas e subjetivas para que possam narrar em profundidade as suas experiências. Com este artigo, procuramos contribuir para o debate sobre esses desafios das pesquisas sobre aborto no Brasil.

En las últimas décadas, se produjo un robusto corpus de investigaciones sobre el aborto en Brasil, con diferentes diseños, objetos y metodologías. Sin embargo, debido a la diversidad de situaciones en las que las mujeres brasileñas vivencian el abortamiento, la complejidad del tema y sus modulaciones en diferentes contextos políticos y socioculturales, el tema continúa desafiando a la academia, el campo de la salud y los derechos reproductivos. En este artículo, presentamos aspectos metodológicos de un estudio cualitativo sobre los itinerarios de cuidados de la salud de mujeres en situación de abortamiento, componente de la encuesta Nacer en Brasil II, que tiene como objetivo discutir los efectos de las desigualdades de género, raza/etnia, clase social, generacionales, regionales y territoriales en esos recorridos. Discutimos el desarrollo del diseño del estudio, la construcción del marco teórico y los recortes analíticos específicos, la elaboración del instrumento de entrevista, los criterios de selección de las mujeres, las estrategias de abordaje y realización de las entrevistas, el manejo del flujo del campo y de los materiales producidos, los procedimientos analíticos y los problemas éticos. Para abarcar una diversidad de mujeres y profundizar los resultados del componente cuantitativo de Nacer en Brasil II, se realizarán 120 entrevistas narrativas. El contexto de criminalización del aborto impacta la producción de conocimiento sobre el tema, imponiendo desafíos, tales como conseguir acceso a las mujeres, asegurar su anonimato y privacidad y la confidencialidad de la información, generar condiciones objetivas y subjetivas para que puedan narrar en profundidad sus experiencias. Con este artículo buscamos contribuir al debate sobre estos desafíos de las investigaciones sobre el aborto en Brasil.

Detection of Mtb and NTM: preclinical validation of a new asymmetric PCR-binary deoxyribozyme sensor assay.

Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.

Quantity and quality are increasing but there's room for improvement: A scoping review of physical activity intervention trials.

BACKGROUND: Observing trends in research publications helps to identify the quantity and quality of research produced, as well as reveal evidence gaps. No comprehensive review of the quality and quantity of physical activity intervention trials has been conducted. OBJECTIVE: We aimed to investigate i) the volume and quality (and changes in these over time) of randomized controlled trials evaluating physical activity interventions, and ii) the association between journal ranking and trial quality. METHODS: We searched the Physiotherapy Evidence Database (PEDro) for trials investigating physical activity interventions (no restrictions for population, comparison, or language). Descriptive statistics were used to describe the volume and quality of trials. The association between journal ranking (Journal Impact Factor) and trial quality (PEDro Scale) was examined using Spearman's rho correlation. RESULTS: We identified 1779 trials, of which 40% (n = 710) were published between 2016 and 2020. The mean (SD) total PEDro score was 5.3 (1.5) points out of 10, increasing over time from 2.5 (0.7) points in 1975-1980 to 5.6 (1.4) points in 2016-2020. Quality criteria that were least reported included blinding of intervention deliverers (therapists) (n = 3, 0.2%), participants (n = 21, 1.2%), or assessors (n = 541, 31%); concealed allocation to groups (n = 526, 30%); and intention to treat analysis (n = 764, 43%). There was a small correlation between trial quality and Journal Impact Factor (0.21, p < 0.001). CONCLUSION: A large volume of trials has investigated physical activity interventions. The quality of these trial reports is suboptimal but improving over time. Journal ranking should not be used for selecting high quality trials.

Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Legacy Mercury Re-emission and Subsurface Migration at Contaminated Sites Constrained by Hg Isotopes and Chemical Speciation.

The re-emission and subsurface migration of legacy mercury (Hg) are not well understood due to limited knowledge of the driving processes. To investigate these processes at a decommissioned chlor-alkali plant, we used mercury stable isotopes and chemical speciation analysis. The isotopic composition of volatilized Hg(0) was lighter compared to the bulk total Hg (THg) pool in salt-sludge and adjacent surface soil with mean ε202HgHg(0)-THg values of -3.29 and -2.35‰, respectively. Hg(0) exhibited dichotomous directions (E199HgHg(0)-THg = 0.17 and -0.16‰) of mass-independent fractionation (MIF) depending on the substrate from which it was emitted. We suggest that the positive MIF enrichment during Hg(0) re-emission from salt-sludge was overall controlled by the photoreduction of Hg(II) primarily ligated by Cl- and/or the evaporation of liquid Hg(0). In contrast, O-bonded Hg(II) species were more important in the adjacent surface soils. The migration of Hg from salt-sludge to subsurface soil associated with selective Hg(II) partitioning and speciation transformation resulted in deep soils depleted in heavy isotopes (δ202Hg = -2.5‰) and slightly enriched in odd isotopes (Δ199Hg = 0.1‰). When tracing sources using Hg isotopes, it is important to exercise caution, particularly when dealing with mobilized Hg, as this fraction represents only a small portion of the sources.

Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications?

Oxysterol sulfates are emerging as key players in lipid homeostasis, inflammation and immunity. Despite this, knowledge on their basal levels in fluids, cells and tissues and any changes associated with age, gender and diet in health and disease; as well as their spatio-temporal distribution in cell membranes and organelles have been greatly hampered by the lack of commercially available pure synthetic standards. Expansion of the panel of pure oxysterol sulfates standards is pivotal to improve our understanding on the impact of oxysterol sulfates at the membrane level and their role in cellular events. While the clinical significance, biophysical implications and biological relevance of oxysterol sulfates in fluids, cells and tissues remains largely unknown, knowledge already gathered on the precursors of oxysterol sulfates (e.g. oxysterols and cholesterol sulfate) can be used to guide researchers on the most relevant aspects to search for when screening for oxysterol sulfates bioavailability in (patho)physiological conditions which are crucial in the design of biophysical and of cell-based assays. Herein, we provide a review on the brief knowledge involving oxysterol sulfate and an overview on the biophysical implications and biological relevance of oxysterols and cholesterol sulfate useful to redirect further investigations on the role of oxysterol sulfates in health and disease.

Systematic SARS-CoV-2 S-gene sequencing in wastewater samples enables early lineage detection and uncovers rare mutations in Portugal.

As the COVID-19 pandemic reached its peak, many countries implemented genomic surveillance systems to track the evolution and transmission of SARS-CoV-2. Transition from the pandemic to the endemic phase prioritized alternative testing strategies to maintain effective epidemic surveillance at the population level, with less intensive sequencing efforts. One such promising approach was Wastewater-Based Surveillance (WBS), which offers non-invasive, cost-effective means for analysing virus trends at the sewershed level. From 2020 onwards, wastewater has been recognized as an instrumental source of information for public health, with national and international authorities exploring options to implement national wastewater surveillance systems and increasingly relying on WBS as early warning of potential pathogen outbreaks. In Portugal, several pioneer projects joined the academia, water utilities and Public Administration around WBS. To validate WBS as an effective genomic surveillance strategy, it is crucial to collect long term performance data. In this work, we present one year of systematic SARS-CoV-2 wastewater surveillance in Portugal, representing 35 % of the mainland population. We employed two complementary methods for lineage determination - allelic discrimination by RT-PCR and S-gene sequencing. This combination allowed us to monitor variant evolution in near-real-time and identify low-frequency mutations. Over the course of this year-long study, spanning from May 2022 to April 2023, we successfully tracked the dominant Omicron sub-lineages, their progression and evolution, which aligned with concurrent clinical surveillance data. Our results underscore the effectiveness of WBS as a tracking system for virus variants, with the ability to unveil mutations undetected via massive sequencing of clinical samples from Portugal, demonstrating the ability of WBS to uncover new mutations and detect rare genetic variants. Our findings emphasize that knowledge of the genetic diversity of SARS-CoV-2 at the population level can be extended far beyond via the combination of routine clinical genomic surveillance with wastewater sequencing and genotyping.

Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats?

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.

A low dose of benzo(a)pyrene during prepuberty in male rats generated immediate oxidative stress in the testes and compromised steroidogenic enzymes/proteins.

The prepubertal period is crucial for sexual development and any alterations can interfere with the reproductive system in adulthood. The aim of this study was to evaluate how Benzo(a)pyrene (BaP) can affect the testes during the prepubertal period. Juvenile male Wistar rats were divided into a control (corn oil + DMSO) and a BaP-group (0.1 µg/kg/day), exposed to BaP for 31 days (gavage), and all parameters were evaluated on postnatal day (PND) 54. Leukocyte counts were decreased. Histological analyses of the testes revealed that height and seminiferous tubules diameters (STDs) were reduced, tubular dynamics were altered, and Leydig cell atrophy was evident in the BaP-group. The testosterone concentration was decreased while FSH levels increased within the BaP-exposed group. Steroidogenic enzymes in the testes were decreased, but steroidogenic acute regulatory protein was not altered. The expression of gstp1 and ckit enzymes was decreased. Reduced glutathione (GSH) and superoxide dismutase (SOD) were increased, whereas malondialdehyde (MDA) was decreased in the testes. In conclusion, BaP or its metabolites causes low systemic toxicity; however, it adversely influences testicular function by disrupting the hormonal axis, unbalancing testicular antioxidative, and blocking the action of the steroidogenic mechanisms.

Dietary (poly)phenols as modulators of the biophysical properties in endothelial cell membranes: its impact on nitric oxide bioavailability in hypertension.

Hypertension is a major contributor to premature death, owing to the associated increased risk of damage to the heart, brain and kidneys. Although hypertension is manageable by medication and lifestyle changes, the risk increases with age. In an increasingly aged society, the incidence of hypertension is escalating, and is expected to increase the prevalence of (cerebro)vascular events and their associated mortality. Adherence to plant-based diets improves blood pressure and vascular markers in individuals with hypertension. Food flavonoids have an inhibitory effect towards angiotensin-converting enzyme (ACE1) and although this effect is greatly diminished upon metabolization, their microbial metabolites have been found to improve endothelial nitric oxide synthase (eNOS) activity. Considering the transmembrane location of ACE1 and eNOS, the ability of (poly)phenols to interact with membrane lipids modulate the cell membrane's biophysical properties and impact on nitric oxide (· NO) synthesis and bioavailability, remain poorly studied. Herein, we provide an overview of the current knowledge on the lipid remodeling of endothelial membranes with age, its impact on the cell membrane's biophysical properties and · NO permeability across the endothelial barrier. We also discuss the potential of (poly)phenols and other plant-based compounds as key players in hypertension management, and address the caveats and challenges in adopted methodologies.

Emergency department contribution to HCV elimination in the Iberian Peninsula.

BACKGROUND: Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas. METHODS: An opportunistic automated HCV screening program was implemented in the EDs of 4 public hospitals in Spain and Portugal at different periods between 2018 and 2023. HCV prevalence was prospectively evaluated, and single-step or reflex testing was used for confirmation in the same sample. RESULTS: More than 90% of the population eligible for testing were screened in the participating centers. We found HCV antibody seroprevalence rates ranging from 0.6 to 3.9%, with between 19 and 53% of viremic individuals. CONCLUSIONS: Opportunistic HCV screening in EDs is feasible, does not disrupt ED activities, is highly effective in increasing diagnosis, and contributes to WHO's HCV elimination goals.

A mixture of glyphosate and 2,4-D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice.

The consumption of Western diet (WD) - enriched in fats and sugars - is associated with overweight, obesity and male reproductive disorders. In addition to WD intake, crops and dairy products display residues of herbicides, including glyphosate and 2,4-D that are widely applied worldwide. The concomitant exposure to WD and herbicides - mimicking contemporary scenarios - is not fully investigated. Thus, we evaluated the effects of glyphosate and 2,4-D, alone or in mixture, on WD-induced alterations in the male genital system. Male C57BL6J mice were submitted to WD (chow containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 months. Concomitantly to WD, the animals received glyphosate (0.05, 5, or 50 mg/kg/day), 2,4-D (0.02, 2 or 20 mg/kg/day) or their mixture (0, 05 + 0.02, 5 + 2, or 50 + 20 mg/kg/day) by intragastrical administration (5×/week). Doses were based on Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) values. Herbicide exposure did not alter the WD-induced obesity, hypercholesterolemia and hyperglycemia. WD induced sperm cell abnormalities, reduced the number, volume and area of Leydig cells, enhanced the frequency of epididymal abnormalities, decreased the proliferation in both germinal and epididymal epithelia, and reduced the number of androgen receptor (AR) positive epididymal cells. Remarkably, the herbicide mixtures promoted such WD-induced effects: increased the frequency of sperm cell and epididymal abnormalities (absence of sperm, cytoplasmic vacuoles, and clear cell hypertrophy) (5 + 2 and 50 + 20 doses); decreased Leydig cell nuclei volume and area (5 + 2 and 50 + 20 doses), reduced epididymal cell proliferation (all mixtures), and AR expression (50 + 20 dose). In addition, herbicide mixtures reduced serum testosterone levels (5 + 2 and 50 + 20 doses). Our findings indicate that the mixture of glyphosate and 2,4-D herbicides, mimicking environmentally relevant scenarios, promotes WD-induced changes in the male genital system.

Effects of L-Dopa, SKF-38393, and quinpirole on exploratory, anxiety- and depressive-like behaviors in pubertal female and male mice.

Adolescence is a phase of substantial changes in the brain, characterized by maturational remodeling of many systems. This remodeling allows functional plasticity to adapt to a changing environment. The dopaminergic system is under morphological and physiological changes during this phase. In the present study, we investigated if changes in the dopaminergic tone alter mice behavior in a receptor and sex-specific manner, specifically at the beginning of the puberty period. We administered L-Dopa, SKF-38393 (D1 dopamine receptor agonist), and Quinpirole (D2 dopamine receptor agonist) and tested male and female mice's motor, anxiety- and depressive-like behavior. While females displayed an impaired exploratory drive, males presented an intense depressive-like response. Our results provide insights into the function of dopaminergic development in adolescent behavior and highlight the importance of studies in this time window with male and female subjects.

Aporte espiritual/religioso pela enfermagem no tratamento do câncer de mama: revisão integrativa / Spiritual/religious support for nursing in the treatment of breast cancer: integrative review / Apoyo espiritual/religioso de la enfermería en el tratamiento del cáncer de mama: revisión integrativa

Objetivo: analisar na literatura científica a importância da abordagem espiritual/religiosa pela equipe de enfermagem no tratamento do câncer de mama. Método: revisão integrativa, realizada na BDENF, LILACS e SCOPUS. Resultados: foram selecionados seis estudos, evidenciou-se que a abordagem espiritual/religiosa pelos profissionais de enfermagem auxilia para o enfrentamento positivo do câncer de mama. Assim, emergiu a categoria.: Abordagem espiritual/religiosa na assistência de enfermagem e suas repercussões positivas para o enfrentamento do câncer de mama. Conclusão: a categoria da enfermagem integra a rede de apoio social para o alívio do sofrimento, por meio do aporte espiritual/religioso, auxiliando para a minimização de sentimentos negativos associados ao diagnóstico e aos eventos adversos dos tratamentos, sendo importante incluir discussões acerca desta temática na formação de nível técnico e graduação em enfermagem.

Objective: to analyze in the scientific literature the importance of the spiritual/religious approach by the nursing team in the treatment of breast cancer. Method: integrative review, carried out in BDENF, LILACS and SCOPUS. Results: six studies were selected, showing that the spiritual/religious approach by nursing professionals helps to cope positively with breast cancer. Thus, the following category emerged: Spiritual/religious approach in nursing care and its positive repercussions for coping with breast cancer. Conclusion: the nursing category is part of the social support network for relieving suffering, through spiritual/religious support, helping to minimize negative feelings associated with the diagnosis and adverse treatment events, and it is important to include discussions on this topic in technical and undergraduate nursing training.

Objetivos:analizar la importancia del abordaje espiritual/religioso por el equipo de enfermería en el tratamiento del cáncer de mama en la literatura científica. Método: revisión integradora, realizada en BDENF, LILACS y SCOPUS. Resultados: fueron seleccionados seis estudios que demuestran que el abordaje espiritual/religioso por profesionales de enfermería ayuda a enfrentar positivamente el cáncer de mama. Surgió la siguiente categoría: Enfoque espiritual/religioso en los cuidados de enfermería y sus repercusiones positivas para el afrontamiento del cáncer de mama. Conclusión: la categoría de enfermería forma parte de la red de apoyo social para aliviar el sufrimiento, a través del apoyo espiritual/religioso, ayudando a minimizar los sentimientos negativos asociados al diagnóstico y a los eventos adversos de los tratamientos, siendo importante incluir discusiones sobre este tema en la formación técnica y de pregrado de enfermería.

2,3,5-triphenyl tetrazolium chloride as colorimetric indicator for drug susceptibility testing against nontuberculous mycobacteria.

This study aimed to propose and evaluate a drug susceptibility testing (DST) using the 2,3,5-triphenyl tetrazolium chloride (TTC) as a colorimetric indicator against Mycobacterium abscessus complex (MABC), M. avium complex (MAC), and M. kansasii strains, main nontuberculous mycobacteria (NTM) of clinical relevance. Our results demonstrated that the assay using TTC and the broth microdilution method recommended by the Clinical and Laboratory Standards Institute had essential agreement above 91%, 92%, and 100%, for drugs tested against MABC, MAC, and M. kansasii strains, respectively. Categorical agreement above 91% was obtained for most drugs tested against MABC, except to cefoxitin (76.5%). For drugs tested against MAC and M. kansasii, categorical agreement above 92% and 100% was observed, respectively. TTC showed to be a promising colorimetric indicator of growth to be used in DST for NTM, allowing an easier reading of results.

Individual differences in rhythm perception modulate music-related motor learning: a neurobehavioral training study with children.

Rhythm and motor function are intrinsically linked to each other and to music, but the rhythm-motor interplay during music training, and the corresponding brain mechanisms, are underexplored. In a longitudinal training study with children, we examined the role of rhythm predisposition in the fine motor improvements arising from music training, and which brain regions would be implicated. Fifty-seven 8-year-olds were assigned to either a 6-month music training (n = 21), sports training (n = 18), or a control group (n = 18). They performed rhythm and motor tasks, and structural brain scans before and after training were collected. Better ability to perceive rhythm before training was related to less gray matter volume in regions of the cerebellum, fusiform gyrus, supramarginal gyrus, ventral diencephalon, amygdala, and inferior/middle temporal gyri. Music training improved motor performance, and greater improvements correlated with better pre-training rhythm discrimination. Music training also induced a loss of gray matter volume in the left cerebellum and fusiform gyrus, and volume loss correlated with higher motor gains. No such effects were found in the sports and control groups. In summary, children with finer-tuned rhythm perception abilities were prone to finer motor improvements through music training, and this rhythm-motor link was to some extent subserved by the left cerebellum and fusiform gyrus. These findings have implications for models on music-related plasticity and rhythm cognition, and for programs targeting motor function.

End-to-End Solution for Analog Gauge Monitoring Using Computer Vision in an IoT Platform.

The emergence of Industry 4.0 and 5.0 technologies has enabled the digital transformation of various processes and the integration of sensors with the internet. Despite these strides, many industrial sectors still rely on visual inspection of physical processes, especially those employing analog gauges. This method of monitoring introduces the risk of human errors and inefficiencies. Automating these processes has the potential, not only to boost productivity for companies, but also potentially reduce risks for workers. Therefore, this paper proposes an end-to-end solution to digitize analog gauges and monitor them using computer vision through integrating them into an IoT architecture, to tackle these problems. Our prototype device has been designed to capture images of gauges and transmit them to a remote server, where computer vision algorithms analyze the images and obtain gauge readings. These algorithms achieved adequate robustness and accuracy for industrial environments, with an average relative error of 0.95%. In addition, the gauge data were seamlessly integrated into an IoT platform leveraging computer vision and cloud computing technologies. This integration empowers users to create custom dashboards for real-time gauge monitoring, while also enabling them to set thresholds, alarms, and warnings, as needed. The proposed solution was tested and validated in a real-world industrial scenario, demonstrating the solution's potential to be implemented in a large-scale setting to serve workers, reduce costs, and increase productivity.