Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy.

The brain contains thousands of millions of synapses, exhibiting diverse structural, molecular, and functional characteristics. However, synapses can be classified into two primary morphological types: Gray's type I and type II, corresponding to Colonnier's asymmetric (AS) and symmetric (SS) synapses, respectively. AS and SS have a thick and thin postsynaptic density, respectively. In the cerebral cortex, since most AS are excitatory (glutamatergic), and SS are inhibitory (GABAergic), determining the distribution, size, density, and proportion of the two major cortical types of synapses is critical, not only to better understand synaptic organization in terms of connectivity, but also from a functional perspective. However, several technical challenges complicate the study of synapses. Potassium ferrocyanide has been utilized in recent volume electron microscope studies to enhance electron density in cellular membranes. However, identifying synaptic junctions, especially SS, becomes more challenging as the postsynaptic densities become thinner with increasing concentrations of potassium ferrocyanide. Here we describe a protocol employing Focused Ion Beam Milling and Scanning Electron Microscopy for studying brain tissue. The focus is on the unequivocal identification of AS and SS types. To validate SS observed using this protocol as GABAergic, experiments with immunocytochemistry for the vesicular GABA transporter were conducted on fixed mouse brain tissue sections. This material was processed with different concentrations of potassium ferrocyanide, aiming to determine its optimal concentration. We demonstrate that using a low concentration of potassium ferrocyanide (0.1%) improves membrane visualization while allowing unequivocal identification of synapses as AS or SS.

Phthalates and substitute plasticizers: Main achievements from the European human biomonitoring initiative HBM4EU.

Phthalates and the substitute plasticizer DINCH belong to the first group of priority substances investigated by the European Human Biomonitoring Initiative (HBM4EU) to answer policy-relevant questions and safeguard an efficient science-to-policy transfer of results. Human internal exposure levels were assessed using two data sets from all European regions and Israel. The first collated existing human biomonitoring (HBM) data (2005-2019). The second consisted of new data generated in the harmonized "HBM4EU Aligned Studies" (2014-2021) on children and teenagers for the ten most relevant phthalates and DINCH, accompanied by a quality assurance/quality control (QA/QC) program for 17 urinary exposure biomarkers. Exposures differed between countries, European regions, age groups and educational levels. Toxicologically derived Human biomonitoring guidance values (HBM-GVs) were exceeded in up to 5% of the participants of the HBM4EU Aligned Studies. A mixture risk assessment (MRA) including five reprotoxic phthalates (DEHP, DnBP, DiBP, BBzP, DiNP) revealed that for about 17% of the children and teenagers, health risks cannot be excluded. Concern about male reproductive health emphasized the need to include other anti-androgenic substances for MRA. Contaminated food and the use of personal care products were identified as relevant exposure determinants paving the way for new regulatory measures. Time trend analyses verified the efficacy of regulations: especially for the highly regulated phthalates exposure dropped significantly, while levels of the substitutes DINCH and DEHTP increased. The HBM4EU e-waste study, however, suggests that workers involved in e-waste management may be exposed to higher levels of restricted phthalates. Exposure-effect association studies indicated the relevance of a range of endpoints. A set of HBM indicators was derived to facilitate and accelerate science-to-policy transfer. Result indicators allow different groups and regions to be easily compared. Impact indicators allow health risks to be directly interpreted. The presented results enable successful science-to-policy transfer and support timely and targeted policy measures.

Prevalence, genetic diversity and eco-epidemiology of pathogenic Leptospira species in small mammal communities in urban parks Lyon city, France.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

Full-length 16S rRNA gene sequencing by PacBio improves taxonomic resolution in human microbiome samples.

BACKGROUND: Sequencing variable regions of the 16S rRNA gene (≃300 bp) with Illumina technology is commonly used to study the composition of human microbiota. Unfortunately, short reads are unable to differentiate between highly similar species. Considering that species from the same genus can be associated with health or disease it is important to identify them at the lowest possible taxonomic rank. Third-generation sequencing platforms such as PacBio SMRT, increase read lengths allowing to sequence the whole gene with the maximum taxonomic resolution. Despite its potential, full length 16S rRNA gene sequencing is not widely used yet. The aim of the current study was to compare the sequencing output and taxonomic annotation performance of the two approaches (Illumina short read sequencing and PacBio long read sequencing of 16S rRNA gene) in different human microbiome samples. DNA from saliva, oral biofilms (subgingival plaque) and faeces of 9 volunteers was isolated. Regions V3-V4 and V1-V9 were amplified and sequenced by Illumina Miseq and by PacBio Sequel II sequencers, respectively. RESULTS: With both platforms, a similar percentage of reads was assigned to the genus level (94.79% and 95.06% respectively) but with PacBio a higher proportion of reads were further assigned to the species level (55.23% vs 74.14%). Regarding overall bacterial composition, samples clustered by niche and not by sequencing platform. In addition, all genera with > 0.1% abundance were detected in both platforms for all types of samples. Although some genera such as Streptococcus tended to be observed at higher frequency in PacBio than in Illumina (20.14% vs 14.12% in saliva, 10.63% vs 6.59% in subgingival plaque biofilm samples) none of the differences were statistically significant when correcting for multiple testing. CONCLUSIONS: The results presented in the current manuscript suggest that samples sequenced using Illumina and PacBio are mostly comparable. Considering that PacBio reads were assigned at the species level with higher accuracy than Illumina, our data support the use of PacBio technology for future microbiome studies, although a higher cost is currently required to obtain an equivalent number of reads per sample.

Acquired enophthalmos in idiopathic orbital inflammatory disease.

Purpose: To describe a rare case of acquired enophthalmos in a patient with idiopathic orbital inflammatory disease after treatment with systemic corticosteroids. Observations: Orbital socket contracture produces a non-traumatic enophthalmos and is most frequently reported as a consequence of orbital trauma or metastatic fibrosis. A previously healthy 64-year-old male presented with 3-month history of binocular diplopia and left proptosis, hypoglobus, supraduction deficit, and compressive neuropathy. Imaging techniques showed a left orbital mass; laboratory tests and biopsy of the mass lead to the diagnosis of idiopathic orbital inflammatory disease. Systemic corticosteroids were administered and, surprisingly, the patient developed left enophthalmos with eyelid retraction. Conclusions and Importance: Although extremely unusual, orbital socket contracture can cause enophthalmos and visual morbidity in patients with idiopathic orbital inflammatory disease treated with corticosteroids.

Muscle mass loss measured with portable ultrasound in hospitalized older adults: The ECOSARC study.

OBJECTIVES: The main objective was to analyze the evolution of muscle of the Quadriceps Rectus Femoris (QRF) between admission and discharge, in older adults hospitalized with an acute medical disease in Acute Geriatric Units (AGUs). DESIGN: Prospective multicentric observational cohort study. SETTING: Seven AGUs from University Hospitals in Spain. PARTICIPANTS: Hospitalized adults ≥ 70 years old, able to ambulate and without severe dementia. MEASUREMENTS: Ultrasound measurements of QRF were acquired at 2/3 distal between anterior-superior iliac spine and patella in both legs by trained Geriatricians. Ultrasound Chison model ECO2 was used. QRF area, thickness, edema, echogenicity, and fasciculations were measured. RESULTS: From the complete sample (n = 143), in 45 (31.5%) participants, ultrasound images were classified as non-valid by an expert radiologist. Mean age was 87.8 (SD 5.4). Mean hospital stay 7.6 days (SD 4.3). From those with valid images, 36 (49.3%), 2 (2.7%), and 35 (47.9%) presented a decrease, equal values, or an increase in QRF area from baseline to discharge, respectively, and 37 (50.0%), 2 (2.7%), and 35 (47.3%) presented a decrease, equal values, or an increase in QRF thickness, respectively. 26 (35.6%) presented a decrease in more than 0.2 cm2 of QRF area, and 23 (31.1%) a decrease in more than 0.1 cm of QRF thickness. Only 4 (5.4%) patients presented new edema, while 13 (17.6%) worsened echogenicity. CONCLUSION: One third of older adults develop significant muscle loss during a hospitalization for acute medical diseases. TRIAL REGISTRATION NUMBER: NCT05113758.

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis.

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. Impact and implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Effectiveness of a randomized intervention by a geriatric team in frail hospital inpatients in non-geriatric settings: FRAILCLINIC project.

BACKGROUND: Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non-geriatric hospital settings on mortality and functional decline after discharge. METHODS: Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non-geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention-to-treat (ITT) and per-protocol (PP) analyses were used. RESULTS: Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47-0.96), P-value 0.027 and 0.29(0.14-0.57), P-value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51-1.01), P-value: 0.055; and 0.64 (0.37-1.10), P-value: 0.105, respectively]. CONCLUSIONS: An individualized intervention in frail in-patients reduces the risk of functional deterioration and mortality at 3 months of follow-up when a care management plan is designed and followed.

Experimental structure based drug design (SBDD) applications for anti-leishmanial drugs: A paradigm shift?

Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species of Leishmania protozoa, which are spread by the bite of infected sandflies. There are three main forms of the disease: cutaneous leishmaniasis (CL, the most common), visceral leishmaniasis (VL, also known as kala-azar, the most serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation of 30,000 new cases of VL and more than 1 million of CL. New treatments for leishmaniasis are an urgent need, as the existing ones are inefficient, toxic, and/or expensive. We have revised the experimental structure-based drug design (SBDD) efforts applied to the discovery of new drugs against leishmaniasis. We have grouped the explored targets according to the metabolic pathways they belong to, and the key achieved advances are highlighted and evaluated. In most cases, SBDD studies follow high-throughput screening campaigns and are secondary to pharmacokinetic optimization, due to the majoritarian belief that there are few validated targets for SBDD in leishmaniasis. However, some SBDD strategies have significantly contributed to new drug candidates against leishmaniasis and a bigger number holds promise for future development.

Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Multidisciplinary optimization of automotive mega-castings merging classical structural optimization with response-surface-based optimization enhanced by machine learning.

Large high pressure die castings (HPDC), recently referred to as mega-castings, can replace plenty of steel metal sheets usually employed for body-in-white (BIW) structures. They can save manufacturing expense and unleash additional lightweight potential thanks to additional design freedom and material properties. The BIW plays a major role in automotive design since it must fulfill numerous structural targets ranging from stiffness for vehicle dynamics, dynamic responses for NVH (noise, vibration, harshness), driving comfort standards and several passive safety requirements. The use of mega-casting structures leads to additional requirements with respect to castability and material quality. Achieving a lightweight design considering requirements related to crash or castability is a challenge on its own, due to the high computational cost of related simulation techniques. Considering multiple requirements simultaneously, therefore often leads to non-weight-optimal structures. To exploit the full lightweight potential, we present a generative multidisciplinary optimization pipeline for the structural design of automotive mega-casting parts in this paper. The approach combines established methods in automotive industry such as topology optimization and response-surface-based (RSM) optimization and enhances the latter by machine learning (ML) based clustering and classification. In a first step topology optimization is employed to derive optimal load-paths for multidisciplinary loading conditions. For this purpose, casting manufacturing constraints as well as more than hundred linearized loads are used to incorporate NVH and passive safety requirements. In a next step the optimal thickness distribution and rib orientation of the structure is achieved using RSM optimization algorithms for the computationally expensive nonlinear crash and casting simulations. Performance indicators are treated by unsupervised learning based on clustering. This enables classification constraints based on simulation field results from hundreds of samples to be included into RSM optimization. It resolves a typical risk of pure scalar, regression-type targets, where supposed optimal results fail when domain experts examine the full field result of the corresponding simulation. It is shown how this approach is superior in achieving a weight-optimal design and turnaround time compared to a design workflow classically used for BIW structures.

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study.

BACKGROUND: Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer's disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. OBJECTIVE: To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment. METHODS: A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users. RESULTS: Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent. CONCLUSIONS: Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

vulnerabilidad en mujeres víctimas de trata desde un enfoque sociocrítico enfermero: Salud, Derechos Humanos y Objetivos de Desarrollo Sostenible / Vulnerabilidade em mulheres traficadas a partir de uma abordagem de enfermagem sócio-crítica: Saúde, Direitos Humanos e Objectivos de Desenvolvimento Sustentável / Vulnerability in trafficked women from a socio-critical nursing ap- proach: Health, Human Rights and Sustainable Development Goals

Trafficking of women is a serious violation of human rights. It is related to vulnerability, poverty, gender inequality, lack of education and migration processes. This global problem also highlights the noncompliance with the Sustainable Development Goals. This reality brings serious health problems to its victims, a point of interest for nursing action. Thus, this work carried out through the collaborative learning method Jigsaw in the context of an elective course of the fourth year of the Degree in Nursing, aims to critically analyze the consequences of trafficking for women's health, relating it to the violation of their human rights and the incompatibility of this international practice with the achievement of the Sustainable Development Goals, to conclude with recommendations that can guide Nursing to provide more appropriate care from its competence as an activist in health for this group. Multiple actions aimed at the prevention, protection and care of women victims of trafficking have been identified, the conflict is generated at the time of executing them, since the neglect of these women from multiple approaches has been noted.(AU)

La trata de mujeres supone una grave violación de los derechos humanos. Está relacionada con la vulnerabilidad, la pobreza, la desigualdad de género, la desescolarización y con los procesos migratorios. En este problema global destaca además el incumplimiento de los Objetivos de Desarrollo Sostenible. Esta realidad acarrea graves problemas de salud a sus víctimas, punto de interés para la actuación de enfermería. Así, este trabajo realizado mediante el método de aprendizaje colaborativo Jigsaw, en el contexto de una asignatura optativa de cuarto curso del Grado en Enfermería, tiene como objetivo el análisis desde el paradigma socio crítico de las consecuencias que la trata supone para la salud de las mujeres, relacionándolo con la vulneración de sus derechos humanos y la incompatibilidad de esta práctica internacional con la consecución de los Objetivos de Desarrollo Sostenible, para concluir con recomendaciones que puedan orientar a la enfermería a proporcionar cuidados más adecuados desde su competencia como activista en salud. Se han identificado múltiples acciones dirigidas a la prevención, protección y atención de las mujeres víctima de trata, el conflicto se genera a la hora de ejecutarlas, ya que se ha constatado la desatención de estas mujeres desde múltiples enfoques.(AU)

O tráfico de mulheres é uma grave violação dos direitos humanos. Está ligado à vulnerabilidade, pobreza, desigualdade de género, falta de escolaridade e processos de migração. Este problema global também realça o fracasso no cumprimento dos Objectivos de Desenvolvimento Sustentável. Esta realidade causa graves problemas de saúde para as suas vítimas, um ponto de interesse para a acção de enfermagem. Assim, este trabalho, realizado utilizando o método de aprendizagem colaborativa Jigsaw no contexto de uma disciplina opcional no quarto ano do Bacharelato em Enfermagem, visa analisar criticamente as consequências do tráfico para a saúde das mulheres, relacionando o com a violação dos seus direitos humanos e a incompatibilidade desta prática internacional com a realização dos Objectivos de Desenvolvimento Sustentável, para concluir com recomendações que possam orientar a enfermagem no sentido de proporcionar cuidados mais adequados a partir da sua competência como activista de saúde para este grupo. Foram identificadas múltiplas acções que visam a prevenção, protecção e cuidados às mulheres vítimas de tráfico, o conflito surge quando se trata de as implementar, uma vez que se verificou a negligência destas mulheres em relação às múltiplas intervenções.(AU)

COVID persistente: prevalencia, seguimiento y uso de recursos en Atención Primaria / Long COVID: prevalence, monitoring and use of resources in Primary Care

Objetivo: estimar la prevalencia de la COVID persistente, signos y síntomas, y uso de recursos en pacientes en Atención Primaria (AP). Métodos: estudio observacional, descriptivo y retrospectivo de una serie de casos realizado en AP. Se incluyeron pacientes mayores de 18 años positivos para SARS-CoV-2 del 29 de febrero al 15 de abril de 2020. Se registraron variables clínicas y de uso de recursos, desde 4 hasta 39 semanas tras el diagnóstico. Resultados: la edad media de los 267 pacientes fue 57 años (desviación estándar [DE]: 16,0), siendo el 55,8% mujeres. La prevalencia de la COVID persistente fue del 45,7% (intervalo de confianza [IC] 95%: 39,6-51,9), y el 53,3% tuvo síntomas más de 12 semanas. Los síntomas más comunes fueron disnea (45,1%; IC 95%: 36,1-54,3), astenia (42,6%; IC 95%: 33,7-51,9), tos (24,6%; IC 95%: 17,2-33,2) y trastornos neuropsiquiátricos (18%; IC 95%: 11,7-26). El 98,4% de pacientes con COVID persistente precisó seguimiento en AP, con 6,7 (DE: 5,0) citas de media. El 45,1% necesitó pruebas de laboratorio; el 34,4%, radiografías de tórax, y el 41,8%, baja laboral. El 20,5% requirió derivaciones hospitalarias, frente al 3,4% en pacientes sin COVID persistente. Los factores asociados a mayor número de citas con AP incluyeron padecer COVID persistente (razón de riesgo de incidencia [RRI]: 2,9; IC 95%: 2,5-3,4) y precisar baja laboral (RRI: 2,4, IC 95%: 2,1-2,9). Conclusión: casi la mitad de los pacientes seguidos en la primera ola desarrollaron COVID persistente. Los síntomas persistentes más frecuentes fueron disnea, astenia y tos. El uso de recursos fue hasta seis veces mayor en pacientes con COVID persistente, frente a aquellos que no lo desarrollaron. (AU)

Aim: to estimate the prevalence of long COVID, its signs and symptoms and use of resources in adult patients in primary care (PC). Methods: an observational, descriptive, retrospective case series study performed in primary care. Patients older than 18 years positive for SARS-CoV-2 from 29 February until 15 April 2020 were included. Variables related to clinical symptoms and use of resources were recorded from four weeks after diagnosis up to 39 weeks. Results: mean age of the 267 patients was 57 years old (16.0 SD); 55,8% were women. In the acute phase, 61.8% of patients required hospitalization and 43.8% suffered bilateral pneumonia. Long COVID prevalence was 45,7% (95% CI 39.6-51.9), and 53.3% had symptoms lasting longer than 12 weeks. Most common symptoms were dyspnoea (45.1%, 95% CI 36.1-54.3), asthenia (42.6%, 95% CI 33.7-51.9), cough (24.6%, 95% CI 17.2-33.2) and neuropsychiatric disorders (18%, 95% CI 11.7-26.0). A total of 98.4% of long COVID patients contacted primary care during follow-up, with 6.7 (5.0 SD) contacts on average. A total of 45.1%, 34.4% and 41.8% underwent laboratory tests, chest x-rays and required work leave, respectively. Long COVID patients needed more hospital referrals (20.5%) compared to those who did not develop this (3.4%). Factors associated with more primary care appointments included developing long COVID (IRR 2.9, 95% CI 2.5-3.4) and requiring a work leave (IRR 2.4, 95% CI 2.1-2.9). Conclusion: virtually half of patients developed long COVID. Most common chronic symptoms were dyspnoea, asthenia and cough. Use of resources was two to six times greater among long COVID patients, in contrast to those who did not develop long COVID. (AU)

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer

New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow usto detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodeshas evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent abenefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevantresults in this scenario.Materials and Methods: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Webof Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with norestrictions on date and language. The search keywords used were “Prostatic Neoplasms” (MeSh) and “Node-positive” (TextWord) and “Radiotherapy” (MeSh) and (“Androgen Antagonists” (MeSh) or “Antineoplastic Agents, Hormonal” (MeSh)), whichare indexed within the Medical Subject Headings database.Results: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery.However, in this review, we summarise the existing literature for the management of these patients in both scenarios, consideringimaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments.Conclusions: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition ofsecond-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients. (AU)

[Telerehabilitación: evolución de la capacidad funcional, calidad de vida y salud mental en pacientes con covid-19 tras un programa de rehabilitación respiratoria.] / Telerehabilitation: Evolution of functional capacity, quality of life and mental health in COVID-19 patients after a Respiratory Rehabilitation program.

OBJECTIVE: The healthcare approach to rehabilitation has undergone important changes due to the COVID-19 pandemic. The objective of the study was to assess the role of a home respiratory telerehabilitation program based on exercises and education in patients admitted to COVID-19. METHODS: An observational cohort study of COVID-19 patients admitted to General Hospital La Mancha Centro from March to June 2020 was carried out, who were assessed and treated by the rehabilitation, physiotherapy and occupational therapy service. After hospital discharge, the functional capacity, quality of life, mental health and happiness of the patients were assessed by telephone consultation at two, fifteen and thirty days. A descriptive analysis was carried out and for follow-up the McNemar test was used for qualitative variables and Student's t or Wilcoxon paired samples test for quantitative variables. RESULTS: Thirty patients were included in the study. The mean age was 60.9 years, with 50% male and 50% female. 80% of the patients were admitted to the ICU, with a mean of thirty four days. 73.3% of the patients developed ICU-acquired weakness. There are statistically significant changes in functional capacity (Barthel from 57.5 to 90), quality of life (EQ-VAS from 60 to 70), mental health (MHI-5 from 23 to 27) and happiness (Lyubomirsky from 4 to 4.5) of patients at thirty days after discharge. CONCLUSIONS: Patients admitted for COVID-19 and included in the home respiratory rehabilitation program through telerehabilitation significantly improve their functional capacity, quality of life, mental health, and happiness during follow-up.

OBJECTIVE: El abordaje asistencial de la rehabilitación ha sufrido cambios importantes con motivo de la pandemia de la COVID-19. El objetivo del estudio fue valorar el papel de un programa de telerehabilitación respiratoria domiciliaria basada en ejercicios y educación en pacientes ingresados con COVID-19. METHODS: Se realizó un estudio observacional de una cohorte de pacientes con COVID-19 ingresados en el Hospital General La Mancha Centro desde marzo a junio de 2020, que fueron valorados y tratados por el servicio de rehabilitación, fisioterapia y terapia ocupacional. Tras el alta hospitalaria, se valoró mediante consulta telefónica a los dos, quince y treinta días, la capacidad funcional, la calidad de vida, la salud mental y la felicidad de los pacientes. Se realizó un análisis descriptivo y para el seguimiento se utilizó los test de McNemar para variables cualitativas y t de student o Wilcoxon de muestras apareados para las cuantitativas. RESULTS: Treinta pacientes fueron incluidos en el estudio. La edad media fue de 60,9 años, siendo un 50% hombres y un 50% mujeres. El 80% de los pacientes ingresaron en UCI, con una media de treinta y cuatro días. El 73,3% de los pacientes desarrollaron debilidad adquirida en UCI. Existen cambios estadísticamente significativos sobre capacidad funcional (Barthel de 57,5 a 90), calidad de vida (EVA de 60 a 70), salud mental (MHI5 de 23 a 27) y felicidad (Lyubomirsky de 4 a 4,5) de los pacientes a los treinta días tras el alta hospitalaria. CONCLUSIONS: Los pacientes ingresados por COVID-19 e incluidos en el programa de rehabilitación respiratoria domiciliaria mediante telerehabilitación mejoran de forma significativa su capacidad funcional, calidad de vida, salud mental y felicidad durante su seguimiento.

Cognitive Performance and Exposure to Organophosphate Flame Retardants in Children: Evidence from a Cross-Sectional Analysis of Two European Mother-Child Cohorts.

The knowledge of the effects of organophosphate flame retardants on children's neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children's neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children's urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (ß = -1.30; 95%CI = -2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (ß = -0.98; 95%CI = -2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (ß = -1.42; 95% CI = -2.70; -0.06; p-value = 0.04) and no clear association with DPHP (ß = -1.09; 95% CI = -2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was -0.49 (95%CI = -1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was -0.35 (95%CI = -1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.