Peripapillary Retinoschisis in Glaucoma: A Systematic Review.

PRCIS: Peripapillary retinoschisis may bias optical coherence tomography's monitoring of glaucoma progression. Its impact on glaucoma still remains uncertain. Only two out of the ten included studies illustrated a correlation between peripapillary retinoschisis and glaucoma progression. PURPOSE: The frequent use of optical coherence tomography increased the detection of peripapillary retinoschisis, which poses challenges in the follow-up of glaucoma patients. This systematic review aims to summarize the literature regarding peripapillary retinoschisis in glaucoma, exploring its prevalence, impact on disease, and clinical management implications. METHODS: We searched PubMed, Embase, Web of Science and Scopus with tailored search queries for each platform. All studies had to report peripapillary retinoschisis in glaucoma patients. Exclusion criteria included studies with less than 10 eyes, studies focusing on schisis outside the disc area, with concomitant retinal or optic nerve lesions, with animals, reviews, studies written in non-English language and congress abstracts. RESULTS: Ten studies were included, of which 7 were case-control, one was a cohort study and two were case series.Six studies showed that peripapillary retinoschisis often overlapped pre-existing retinal nerve fiber layer defects. One study reported that the de novo development of peripapillary retinoschisis was more frequent in eyes with glaucoma progression than in eyes without progression.Visual field findings were inconsistent, with just one study (out of six) showing that glaucoma patients with peripapillary retinoschisis experienced faster visual field deterioration than those without it. Overall, solely two studies (out of seven) associated peripapillary retinoschisis with faster glaucoma progression. CONCLUSIONS: Peripapillary retinoschisis biases optical coherence tomography analysis in glaucoma. Caution is needed against overestimation of retinal nerve fiber layer thickness when peripapillary retinoschisis develops, and misinterpretation of its resolution as rapid progression. Peripapillary retinoschisis' exact impact on glaucoma progression remains unclear.

A longer period of epididymal sperm interaction with extender components during cryopreservation improves sperm quality, decreases the size of sperm distal cytoplasmic droplets, and changes the number of nanoparticles in the extender.

While cryopreservation of cauda epididymal sperm (SpCau) allows the preservation of post-mortem bulls' gametes, the process triggers sperm damage. Although improving post-thaw sperm quality, using egg yolk extenders (EY) raises biosafety concerns which forces the use of EY-free extenders (EYFE). Since EYFE are less efficient in preserving post-thaw sperm quality, a strategy for ejaculated sperm (SpEj) frozen with EYFE is to add an Equilibrium Time (ET) step period to the cryopreservation process. However, the ET effect on the quality of SpCau cryopreserved in EYFE remains unknown. Distinct from SpEJ, SpCau physiologically displays cytoplasmic droplets (CDs) in the flagellum that may benefit cell exchange during ET. We hypothesized that using ET in SpCau cryopreserved with EYFE impacts sperm morphofunctional features, CD area, and in vitro fertility ability. Extender nanoparticles were also assessed. Following collection from the cauda epididymis of six Nellore bulls by retrograde flow, SpCau were cryopreserved in EYFE BoviFree® (Minitube, Germany) using three ET protocols: ET0 (no-ET); ET2.5 (2.5 hours-ET); and ET5 (5 hours-ET). SpCau from ET2.5 and ET5 showed a higher (P≤0.05) percentage of motility and integrity of plasma and acrosome membranes and a smaller (P≤0.05) distal CD area. There are no differences in sperm abnormalities, oxidative stress, capacitation-like events, and in vitro fertility ability. However, a better sperm recovery was found after Percoll® selection for ET2.5 and ET5. Interestingly, the number of nanoparticles in the extender decreased in post-thawed samples. In conclusion, an ET of 2.5 or 5 hours is required for an efficient SpCau cryopreservation using an EYFE.

Development of an antibody against EtpA from enterotoxigenic Escherichia coli and evaluation of its use for bacterial isolation using magnetic beads.

The enterotoxigenic Escherichia coli (ETEC) strain is one of the most frequent causative agents of childhood diarrhea and travelers' diarrhea in low-and middle-income countries. Among the virulence factors secreted by ETEC, the exoprotein EtpA has been described as an important. In the present study, a new detection tool for enterotoxigenic E. coli bacteria using the EtpA protein was developed. Initially, antigenic sequences of the EtpA protein were selected via in silico prediction. A chimeric recombinant protein, corresponding to the selected regions, was expressed in an E. coli host, purified and used for the immunization of mice. The specific recognition of anti-EtpA IgG antibodies generated was evaluated using flow cytometry. The tests demonstrated that the antibodiesdeveloped were able to recognize the native EtpA protein. By coupling these antibodies to magnetic beads for the capture and detection of ETEC isolates, cytometric analyses showed an increase in sensitivity, specificity and the effectiveness of the method of separation and detection of these pathogens. This is the first report of the use of this methodology for ETEC separation. Future trials may indicate their potential use for isolating these and other pathogens in clinical samples, thus accelerating the diagnosis and treatment of diseases.

Brazilian Guideline on Menopausal Cardiovascular Health ­ 2024 / Guía Brasileña de Salud Cardiovascular en el Climaterio y la Menopausia ­ 2024 / Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa ­ 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.

Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.

As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios "bioidênticos" "manipulados", e a 'modulação hormonal' não são recomendados pela falta de evidência científica de sua eficácia e segurança.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

Contact tracing management of a measles case in a paediatric hospital: experience of the local public health unit, Portugal, January 2024.

In January 2024, a child was diagnosed with measles in a paediatric hospital in Lisbon. Of 123 contacts, 39 (32%) were not fully immunised, presenting a risk for a potential outbreak. The public health unit initiated control measures and identified challenges during the response, such as the lack of interoperability between information systems and accessing vaccination records. The lessons learned prompted changes to national contact tracing procedures for measles, further strengthening Portugal's preparedness.

Development of a dry powder insufflation device with application in in vitro cell-based assays in the context of respiratory delivery.

Research on pharmaceutical dry powders has been increasing worldwide, along with increased therapeutic strategies for an application through the pulmonary or the nasal routes. In vitro methodologies and tests that mimic the respiratory environment and the process of inhalation itself are, thus, essential. The literature frequently reports cell-based in vitro assays that involve testing the dry powders in suspension. This experimental setting is not adequate, as both the lung and the nasal cavity are devoid of abundant liquid. However, devices that permit powder insufflation over cells in culture are either scarce or technically complex and expensive, which is not feasible in early stages of research. In this context, this work proposes the development of a device that allows the delivery of dry powders onto cell surfaces, thus simulating inhalation more appropriately. Subsequently, a quartz crystal microbalance (QCM) was used to establish a technique enabling the determination of dry powder deposition profiles. Additionally, the determination of the viability of respiratory cells (A549) after the insufflation of a dry powder using the developed device was performed. In all, a prototype for dry powder insufflation was designed and developed, using 3D printing methods for its production. It allowed the homogenous dispersion of the insufflated powders over a petri dish and a QCM crystal, and a more detailed study on how dry powders disperse over the supports. The device, already protected by a patent, still requires further improvement, especially regarding the method for powder weighing and the efficiency of the insufflation process, which is being addressed. The impact of insufflation of air and of locust bean gum (LBG)-based microparticles revealed absence of cytotoxic effect, as cell viability roughly above 70 % was always determined.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms. METHODS AND ANALYSIS: We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings. TRIAL REGISTRATION NUMBER: NCT05913700.

Single-cell Transcriptome Analysis Identifies Senescent Osteocytes as Contributors to Bone Destruction in Breast Cancer Metastasis.

Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression that disrupts the balance between osteoclasts and osteoblasts, leading to bone lesions. Whether such reprogramming affects matrix-embedded osteocytes remains poorly understood. Here, we demonstrate that osteocytes in breast cancer bone metastasis develop premature senescence and a distinctive senescence-associated secretory phenotype (SASP) that favors bone destruction. Single-cell RNA sequencing identified osteocytes from mice with breast cancer bone metastasis enriched in senescence and SASP markers and pro-osteoclastogenic genes. Using multiplex in situ hybridization and AI-assisted analysis, we detected osteocytes with senescence-associated distension of satellites, telomere dysfunction, and p16Ink4a expression in mice and patients with breast cancer bone metastasis. In vitro and ex vivo organ cultures showed that breast cancer cells promote osteocyte senescence and enhance their osteoclastogenic potential. Clearance of senescent cells with senolytics suppressed bone resorption and preserved bone mass in mice with breast cancer bone metastasis. These results demonstrate that osteocytes undergo pathological reprogramming by breast cancer cells and identify osteocyte senescence as an initiating event triggering bone destruction in breast cancer metastases.

Prevalência e fatores de riscos relacionados a comportamentos suicidas em profissionais do sexo / Prevalencia y factores de riesgo relacionados con la conducta suicidal en trabajadores sexuales / Prevalence and risk factors related to suicidal behavior in sex workers

Introdução: O trabalho sexual consentido é, historicamente, permeado por estigmas, proporcionando a marginalização social de profissionais do sexo e sua maior exposição a fatores de riscos que tendenciam a condutas suicidas. Objetivo: Identificar a prevalência e dos fatores de riscos relacionados a comportamentos suicidas em profissionais do sexo, tendo em vista a vulnerabilidade social desse grupo. Metodologia: Este estudo é uma revisão integrativa de literatura, determinada a partir da seguinte questão de pesquisa: "Qual a prevalência e os fatores de riscos relacionados a comportamentos suicidas entre profissionais do sexo?". Em seguida, aplicou os subsequentes Descritores em Ciências da Saúde: "Suicide" e "Sex workers", que foram combinados com o operador booleano "AND", nas plataformas National Library of Medicine, Science Direct, Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Literatura Latino-americana e do Caribe, Scientific Eletronic Library Online, BioMed Central, Business Source Completee WorldWideScience. Foram selecionados 19 artigos relacionados ao objeto de estudo. Resultados: A prevalência de suicídio em profissionais do sexo foi classificada em três subcategorias: tentativas de suicídio, com predominância de 31,57% (n=6), ideação suicida com 15,78% (n=3) e o risco de suicídio com 5,26% (n=1). Os riscos de comportamentos suicidas foram associados a diversos fatores, sobretudo a violência (47,36%; n=9), depressão (26,31%; n=5) e a pobreza (15,78%; n=3). Conclusões: Há uma alta prevalência de comportamentos suicidas em profissionais do sexo que está associada a diversos fatores de riscos, verificando a carência de abordagens comunitárias direcionadas à vulnerabilidade social desse grupo (AU).

Introduction: Consensual sex work has historically been permeated by stigma, leading to the social marginalization of sex workers and their increased exposure to risk factors that tend to correlate with suicidal behaviors. Objective:To explore the prevalence and risk factors related to suicidal behavior in sex workers, considering the social vulnerability of this group. Methodology: This study is an integrative literature review, guided by the research question: "What is the prevalence and risk factors related to suicidal behaviors among sex workers?" The following Health Science Descriptors were applied: "Suicide" and "Sex workers," combined with the boolean operator "AND," on platforms such as the National Library of Medicine, Science Direct, Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Literatura Latino-americana e do Caribe, Scientific Eletronic Library Online, BioMed Central, Business Source Complete, and WorldWideScience. Nineteen articles related to the study's objectivewere selected. Results:The prevalence of suicide among sex workers were classified into three subcategories: suicide attempts, with a predominance of 31.57% (n=6), suicidal ideation with 15.78% (n=3) and the risk of suicide with a prevalence of 5.26% (n=1). The risks of suicidal behavior were associated with several factors, especially violence (47,36%; n=9), depression (26.31%; n=5) and poverty (15.78% /n=3). Conclusions: There is a high prevalence of suicidal behaviors among sex workers, associated with various risk factors, highlighting the need for community-based approaches addressing the social vulnerability of this group (AU).

Introducción: El trabajo sexual consensuado ha estado históricamente impregnado de estigmas, llevando a la marginación social de los profesionales del sexo y a una mayor exposición a factores de riesgo que tienden a asociarse con conductas suicidas. Objetivo: Identificar la prevalencia y los factores de riesgo relacionados con comportamientos suicidas en profesionales del sexo, considerando la vulnerabilidad social de este grupo. Metodología: Este estudio es una revisión integradora de la literatura, derivada de la siguiente pregunta de investigación: "¿Cuál es laprevalencia y los factores de riesgo relacionados con comportamientos suicidas entre los profesionales del sexo?". Posteriormente, se aplicaron los siguientes Descriptores en Ciencias de la Salud: "Suicide" y "Sex workers", combinados con el operador booleano "AND", en plataformas como la Biblioteca Nacional de Medicina, Science Direct, Portal de Periódicos de la Coordinación de Perfeccionamiento de Personal de Nivel Superior, Literatura Latinoamericana y del Caribe, Scientific Electronic Library Online, BioMed Central, Business Source Complete y WorldWideScience. Se seleccionaron 19 artículos relacionados con el objeto de estudio. Resultados: La prevalencia de suicidio en profesionales del sexo se clasificó en tres subcategorías: intentos de suicidio, con una predominancia del 31,57% (n=6), ideación suicida con el 15,78% (n=3) y el riesgo de suicidio con el 5,26% (n=1). Los riesgos de comportamientos suicidas se asociaron con varios factores, especialmente la violencia (47,36%; n=9), la depresión (26,31%; n=5) y la pobreza (15,78%; n=3). Conclusiones: Existe una alta prevalencia de comportamientos suicidas en profesionales del sexo asociada con diversos factores de riesgo, destacando la necesidad de enfoques comunitarios dirigidos a la vulnerabilidad social de este grupo (AU).

Oestradiol and osteoclast differentiation: Effects on p53 and mitochondrial metabolism.

BACKGROUND: Oestrogen deficiency increases bone resorption, contributing to osteoporosis development. Yet, the mechanisms mediating the effects of oestrogen on osteoclasts remain unclear. This study aimed to elucidate the early metabolic alteration induced by RANKL, the essential cytokine in osteoclastogenesis and 17-beta-oestradiol (E2) on osteoclast progenitor cells, using RAW 264.7 macrophage cell line and primary bone marrow-derived macrophages as biological models. RESULTS: This research demonstrated that, in osteoclast precursors, RANKL stimulates complex I activity, oxidative phosphorylation (OXPHOS) and mitochondria-derived ATP production as early as 3 h of exposure. This effect on mitochondrial bioenergetics is associated with an increased capacity to oxidize TCA cycle substrates, fatty acids and amino acids. E2 inhibited all effects of RANKL on mitochondria metabolism. In the presence of RANKL, E2 also decreased cell number and stimulated the mitochondrial-mediated apoptotic pathway, detected as early as 3 h. Further, the pro-apoptotic effects of E2 during osteoclast differentiation were associated with an accumulation of p392S-p53 in mitochondria. CONCLUSIONS: These findings elucidate the early effects of RANKL on osteoclast progenitor metabolism and suggest novel p53-mediated mechanisms that contribute to postmenopausal osteoporosis.

Refining the identity of mesenchymal cell types associated with murine periosteal and endosteal bone.

Single-cell RNA-seq has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single-cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types associated with murine bone. We created an atlas of murine bone-associated cells by harmonizing published datasets with in-house data from cells targeted by Osx1-Cre and Dmp1-Cre driver strains. Cells from periosteal bone were analyzed separately from those isolated from the endosteum and trabecular bone. Over 100,000 mesenchymal cells were mapped to reveal 11 major clusters designated fibro-1, fibro-2, chondrocytes, articular chondrocytes, tenocytes, adipo-Cxcl12 abundant reticular (CAR), osteo-CAR, preosteoblasts, osteoblasts, osteocytes, and osteo-X, the latter defined in part by periostin expression. Osteo-X, osteo-CAR, and preosteoblasts were closely associated with osteoblasts at the trabecular bone surface. Wnt16 was expressed in multiple cell types from the periosteum but not in cells from endocortical or cancellous bone. Fibro-2 cells, which express markers of stem cells, localized to the periosteum but not trabecular bone in adult mice. Suppressing bone remodeling eliminated osteoblasts and altered gene expression in preosteoblasts but did not change the abundance or location of osteo-X or osteo-CAR cells. These results provide a framework for identifying bone cell types in murine single-cell RNA-seq datasets and suggest that osteoblast progenitors reside near the surface of remodeling bone.

A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.

BACKGROUND: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. METHODS: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. RESULTS: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. CONCLUSIONS: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

SQSTM1 Pro392Leu presenting as a corticobasal syndrome with progressive nonfluent aphasia.

Corticobasal syndrome is generally considered to be a sporadic condition. There are familial and isolated genetic cases, associated with GRN, MAPT, c9orf72 or PNRP variants. Some reports implicate other genes: LRRK2, CHMP2B, GBA, CYP27A1, PSEN1, APP, TARDBP and TBK1. Here, we report a case of a patient carrying a SQSTM1 Pro392Leu variant. We report a 57-year-old right-handed-woman with a history of progressive speech impairment, marked right side rigidity and bradykinesia, with rest tremor and stimulus sensitive myoclonus. She had predominantly right-sided apraxia. She had right side agraphestesia and astereognosis. MRI showed asymmetrical left frontotemporoparietal atrophy. DaTSCAN showed predominantly left involvement, PiB-PET was negative. CSF NfL was of 9356.5pg/mL. She carried a heterozygous variant P392L in SQSTM1. This case report expands the spectrum of phenotypes associated with SQSTM1 pathogenic variants. It also expands the list of genes associated with corticobasal syndrome, supporting the involvement of the ubiquitin-proteasome system in this condition.

Towards a practical threat assessment methodology for crop landraces.

Crop landraces (LR), the traditional varieties of crops that have been maintained for millennia by repeated cycles of planting, harvesting, and selection, are genetically diverse compared to more modern varieties and provide one of the key components for crop improvement due to the ease of trait transfer within the crop species. However, LR diversity is increasingly threatened with genetic erosion and extinction by replacement with improved cultivars, lack of incentives for farmers to maintain traditional agricultural systems, and rising threats from climate change. Their active conservation is necessary to maintain this critical resource. However, as there are hundreds of thousands of LR and millions of LR populations for crops globally, active conservation is complex and resource-intensive. To assist in implementation, it is useful to be able to prioritise LR for conservation action and an obvious means of prioritisation is based on relative threat assessment. There have been several attempts to propose LR threat assessment methods, but none thus far has been widely accepted or applied. The aim of this paper is to present a novel, practical, standardised, and objective methodology for LR threat assessment derived from the widely applied IUCN Red Listing for wild species, involving the collation of time series information for LR population range, LR population trend, market, and farmer characteristics and LR context information. The collated information is compared to a set of threat criteria and an appropriate threat category is assigned to the LR when a threshold level is reached. The proposed methodology can be applied at national, regional, or global levels and any crop group.

Late-onset neonatal sepsis was not associated with impaired neurodevelopmental outcome: Results from the EPICE/SHIPS-PT cohort.

AIM: To assess the impact of late-onset neonatal sepsis (LONS) on the cognitive and motor development of five-year-old children who were born very preterm (VPT). METHODS: This study included 327 VPT children from the Portuguese EPICE/SHIPS cohort who attended the neurodevelopment assessment. Neuropsychological tests such as WPPSI-R, MABC-2 and NEPSY-II (language domain) were used to assess the children's cognitive and motor development. Statistical analysis was performed to compare the socio-demographic, clinical and neurodevelopment outcomes of VPT children with and without LONS. Regression analysis adjusted for confounding variables was performed when applicable. RESULTS: Underperformance in intelligence quotient and language development was similar regardless of a neonatal diagnosis of LONS. In contrast, VPT children with LONS had a higher risk of movement difficulties than those without LONS (p = 0.02). However, the association was lost after adjusting for confounders (ß = -0.25; p > 0.05). CONCLUSION: LONS per se was not associated with the risk for poor long-term cognitive or motor outcomes in VPT children. Social-demographic and clinical characteristics assessed during the neonatal period and at the time of neurodevelopment assessment were similar between groups suggesting that social-related factors such as parents' educational level could have mitigated the LONS impact.

Current Understanding of Human Polymorphism in Selenoprotein Genes: A Review of Its Significance as a Risk Biomarker.

Selenium has been proven to influence several biological functions, showing to be an essential micronutrient. The functional studies demonstrated the benefits of a balanced selenium diet and how its deficiency is associated with diverse diseases, especially cancer and viral diseases. Selenium is an antioxidant, protecting the cells from damage, enhancing the immune system response, preventing cardiovascular diseases, and decreasing inflammation. Selenium can be found in its inorganic and organic forms, and its main form in the cells is the selenocysteine incorporated into selenoproteins. Twenty-five selenoproteins are currently known in the human genome: glutathione peroxidases, iodothyronine deiodinases, thioredoxin reductases, selenophosphate synthetase, and other selenoproteins. These proteins lead to the transport of selenium in the tissues, protect against oxidative damage, contribute to the stress of the endoplasmic reticulum, and control inflammation. Due to these functions, there has been growing interest in the influence of polymorphisms in selenoproteins in the last two decades. Selenoproteins' gene polymorphisms may influence protein structure and selenium concentration in plasma and its absorption and even impact the development and progression of certain diseases. This review aims to elucidate the role of selenoproteins and understand how their gene polymorphisms can influence the balance of physiological conditions. In this polymorphism review, we focused on the PubMed database, with only articles published in English between 2003 and 2023. The keywords used were "selenoprotein" and "polymorphism". Articles that did not approach the theme subject were excluded. Selenium and selenoproteins still have a long way to go in molecular studies, and several works demonstrated the importance of their polymorphisms as a risk biomarker for some diseases, especially cardiovascular and thyroid diseases, diabetes, and cancer.

[Body image perception, socioeconomic characteristics, and lifestyle in women participating in ELSA-Brasil in Bahia, Brazil]. / Percepção de imagem corporal, características socioeconômicas e estilo de vida em mulheres participantes do ELSA-Brasil na Bahia, Brasil.

Body image distortion is an alteration in the perception of the body that can have repercussions on health. This study aims to estimate the prevalence of body image accuracy and distortion among women participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) living in Bahia State, Brazil, and to investigate associations with socioeconomic characteristics, lifestyle, and gynecological care seeking. A total of 609 women aged 50 to 69 years participated in the study, who answered face-to-face questionnaires from 2012 to 2014. The Stunkard silhouette scale was used to investigate accurate or distorted perception for more or less weight. The relative risk ratio (RR) was calculated by multinomial logistic regression using Stata 13. Most participants have an accurate perception of their own bodies (53.7%). Among those with distorted perception, there is a tendency to distort towards less weight (38.1%). In the multinomial regression analysis, the variables race/skin color and education remained associated with the distortion towards underweight. The race/skin color variable was positively associated with the distortion towards underweight among Mixed-race women (RR = 1.89; 95%CI: 1.13-3.16) and black (RR = 2.10; 95%CI: 1.25-3.55), while the education variable among those with up to high school education (RR = 1.65; 95%CI: 1.18-2.33). There were no associations with the other variables or with distortion for more weight. The results contribute to explaining the relationships between body image perception and socioeconomic factors, revealing that women of different races/skin colors and varying educational levels are influenced in different ways by social discourses, impacting the perception of their body image.

Distorção da imagem corporal é uma alteração da percepção do corpo que pode repercutir na saúde. Este estudo visa estimar, entre mulheres participantes do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) residentes na Bahia, Brasil, a prevalência de acurácia e distorção da imagem corporal e investigar associações com características socioeconômicas, estilo de vida e procura de cuidados ginecológicos. Participaram 609 mulheres de 50-69 anos de idade que responderam, entre 2012-2014, questionários aplicados face a face. Foi utilizada a escala de silhuetas de Stunkard para investigar a percepção acurada ou distorcida para mais ou menos peso. A razão de risco relativo (RR) foi calculada por meio de regressão logística multinomial por meio do Stata 13. A maioria das participantes tem perspectiva acurada do próprio corpo (53,7%). Entre aquelas com percepção distorcida, há uma tendência à distorção para menos peso (38,1%). Na análise de regressão multinomial, permaneceram associadas à distorção para menos peso as variáveis raça/cor e escolaridade, sendo que a primeira foi positivamente associada à distorção para menos peso entre as pardas (RR = 1,89; IC95%: 1,13-3,16) e pretas (RR = 2,10; IC95%: 1,25-3,55), enquanto a segunda entre aquelas com escolaridade até o Ensino Médio (RR = 1,65; IC95%: 1,18-2,33). Não houve associações quanto às demais variáveis, nem com distorção para mais peso. Os resultados contribuem para a explicação das relações entre percepção da imagem corporal e fatores socioeconômicos, revelando que mulheres de raça/cor diferentes e variados níveis de escolaridade são influenciadas de formas distintas pelos discursos sociais, o que impacta a percepção da sua imagem corporal.

La distorsión de la imagen corporal es una alteración en la percepción del cuerpo que puede repercutir en la salud. Este estudio busca estimar, entre las mujeres participantes del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil) que viven en Bahía, Brasil, la prevalencia de precisión y distorsión de la imagen corporal e investigar asociaciones con las características socioeconómicas, el estilo de vida y la busca de atención ginecológica. Participaron 609 mujeres que tenían entre 50 y 69 años que contestaron los cuestionarios aplicados cara a cara entre 2012 y 2014. Se utilizó la escala de siluetas de Stunkard para investigar la percepción precisa o distorsionada para más o menos peso. El cociente de riesgo relativo (RR) se calculó a través de regresión logística multinomial utilizando el Stata 13. La mayoría de los participantes tiene una perspectiva precisa del propio cuerpo (53,7%). Entre las personas con percepción distorsionada hay una tendencia a la distorsión para menos peso (38,1%). En el análisis de regresión multinomial, las variables raza/color y escolaridad permanecieron asociadas con la distorsión para menos peso, siendo la primera positivamente asociada con la distorsión para menos peso entre las mujeres pardas (RR = 1,89; IC95%: 1,13-3,16) y negras (RR = 2,10; IC95%: 1,25-3,55), mientras la segunda entre las mujeres que estudiaron hasta la enseñanza secundaria (RR = 1,65; IC95%: 1,18-2,33). No hubo asociaciones con las otras variables ni con la distorsión para más peso. Los resultados contribuyen para explicar las relaciones entre la percepción de la imagen corporal y los factores socioeconómicos, demostrando que mujeres de diferentes razas/colores y diferentes niveles de educación se influyen de distintas formas a través de discursos sociales, lo que impacta en la percepción de su imagen corporal.