Progressive alterations in polysomal architecture and activation of ribosome stalling relief factors in a mouse model of Huntington's disease.

Given their highly polarized morphology and functional singularity, neurons require precise spatial and temporal control of protein synthesis. Alterations in protein translation have been implicated in the development and progression of a wide range of neurological and neurodegenerative disorders, including Huntington's disease (HD). In this study we examined the architecture of polysomes in their native brain context in striatal tissue from the zQ175 knock-in mouse model of HD. We performed 3D electron tomography of high-pressure frozen and freeze-substituted striatal tissue from HD models and corresponding controls at different ages. Electron tomography results revealed progressive remodelling towards a more compacted polysomal architecture in the mouse model, an effect that coincided with the emergence and progression of HD related symptoms. The aberrant polysomal architecture is compatible with ribosome stalling phenomena. In fact, we also detected in the zQ175 model an increase in the striatal expression of the stalling relief factor EIF5A2 and an increase in the accumulation of eIF5A1, eIF5A2 and hypusinated eIF5A1, the active form of eIF5A1. Polysomal sedimentation gradients showed differences in the relative accumulation of 40S ribosomal subunits and in polysomal distribution in striatal samples of the zQ175 model. These findings indicate that changes in the architecture of the protein synthesis machinery may underlie translational alterations associated with HD, opening new avenues for understanding the progression of the disease.

Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

Translational Control of Alphavirus-Host Interactions: Implications in Viral Evolution, Tropism and Antiviral Response.

Alphaviruses can replicate in arthropods and in many vertebrate species including humankind, but only in vertebrate cells do infections with these viruses result in a strong inhibition of host translation and transcription. Translation shutoff by alphaviruses is a multifactorial process that involves both host- and virus-induced mechanisms, and some of them are not completely understood. Alphavirus genomes contain cis-acting elements (RNA structures and dinucleotide composition) and encode protein activities that promote the translational and transcriptional resistance to type I IFN-induced antiviral effectors. Among them, IFIT1, ZAP and PKR have played a relevant role in alphavirus evolution, since they have promoted the emergence of multiple viral evasion mechanisms at the translational level. In this review, we will discuss how the adaptations of alphaviruses to vertebrate hosts likely involved the acquisition of new features in viral mRNAs and proteins to overcome the effect of type I IFN.

The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A.

Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), which then scans along the mRNA until the start codon is recognized. We have previously shown that eIF4F binds near the mRNA exit channel of the 43S, leaving open the question of how mRNA secondary structure is removed as it enters the mRNA channel on the other side of the 40S subunit. Here we report the structure of a human 48S that shows that, in addition to the eIF4A that is part of eIF4F, there is a second eIF4A helicase bound at the mRNA entry site, which could unwind RNA secondary structures as they enter the 48S. The structure also reveals conserved interactions between eIF4F and the 43S, probaby explaining how eIF4F can promote mRNA recruitment in all eukaryotes.

STIM1 translocation to the nucleus protects cells from DNA damage.

DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair.

The molecular basis of translation initiation and its regulation in eukaryotes.

The regulation of gene expression is fundamental for life. Whereas the role of transcriptional regulation of gene expression has been studied for several decades, it has been clear over the past two decades that post-transcriptional regulation of gene expression, of which translation regulation is a major part, can be equally important. Translation can be divided into four main stages: initiation, elongation, termination and ribosome recycling. Translation is controlled mainly during its initiation, a process which culminates in a ribosome positioned with an initiator tRNA over the start codon and, thus, ready to begin elongation of the protein chain. mRNA translation has emerged as a powerful tool for the development of innovative therapies, yet the detailed mechanisms underlying the complex process of initiation remain unclear. Recent studies in yeast and mammals have started to shed light on some previously unclear aspects of this process. In this Review, we discuss the current state of knowledge on eukaryotic translation initiation and its regulation in health and disease. Specifically, we focus on recent advances in understanding the processes involved in assembling the 43S pre-initiation complex and its recruitment by the cap-binding complex eukaryotic translation initiation factor 4F (eIF4F) at the 5' end of mRNA. In addition, we discuss recent insights into ribosome scanning along the 5' untranslated region of mRNA and selection of the start codon, which culminates in joining of the 60S large subunit and formation of the 80S initiation complex.

Prospective study of cenobamate on cognition, affectivity, and quality of life in focal epilepsy.

OBJECTIVE: Cenobamate is a recently approved antiseizure medication that proved to be safe and effective in randomized controlled trials. However, little is known about its impact on some areas frequently affected by epilepsy. For this reason, we explored the effects of cenobamate on cognitive performance, as well as on negative affectivity and quality of life in a sample of patients with drug-resistant epilepsy. METHODS: Two prospective cohort studies were carried out. In Study 1, 32 patients (22 men and 10 women) underwent a baseline (T0) and a short-term (T1) neuropsychological assessment after 3 months of cenobamate administration. In Study 2, 22 patients (16 men and 6 women) from the T1 sample also underwent a baseline and a follow-up evaluation (T2) 6 months after T0. RESULTS: No significant differences were found in cognitive variables, negative affectivity, and quality of life either in Study 1 or Study 2. Similarly, based on the reliable change index, it was found that most patients showed no changes in these variables. SIGNIFICANCE: These results suggest that cenobamate is a safe antiseizure medication in terms of cognition, negative affectivity, or quality of life since no adverse events have been found after 3 and 6 months of treatment. PLAIN LANGUAGE SUMMARY: Cenobamate is a new antiseizure medication. In patients with epilepsy, cenobamate seems to not affect cognition, anxiety, depression, or quality of life.

Content Validity of the Spanish Adaptation of the Premature Infant Pain Profile Revised.

BACKGROUND: To the best of our knowledge, there are no validated neonatal pain assessment scales in Spanish. Given the need for such a scale, a study was undertaken to adapt and validate the Premature Infant Pain Profile-Revised (PIPP-R) scale. After translation and back-translation, content validity was addressed, a crucial phase in validation studies, in which researchers examine whether the items that make up the scale represent the content that the scale is intended to assess. AIMS: The aim was to provide evidence for the content validity of the Spanish adaptation of the PIPP-R scale. METHOD: The study used the Delphi technique with 10 experts. Data collection was anonymous and was conducted through an online platform. It was an ad hoc survey consisting of four questions, with a five-point Likert scale for each item on the scale and for the instruction table. An item-content validity index (I-CVI) and a scale-content validity index (S-CVI) were calculated for the analysis. RESULTS: After two rounds of the survey, all items exceeded an I-CVI of 0.9. The S-CVI value was 0.98 (±0.03) for the scale, and 1 for its instruction table. The kappa index yielded values indicating an excellent degree of agreement. CONCLUSIONS: The Spanish version of the PIPP-R obtained a high degree of content validity according to the expert group and the Delphi technique.

Impact of Polytherapy on Memory Functioning in Patients With Drug-Resistant Epilepsy: The Role of Attention and Executive Functions.

OBJECTIVE: The aim was to examine the effect of polytherapy (i.e., the number of administered anti-seizure medications (ASMs)) on memory, and whether the interaction between the number of ASMs and attentional/executive functioning affect presurgical memory functioning and postsurgical memory changes in patients with drug-resistant epilepsy. METHODS: Two studies were carried out. Study 1 consisted of a presurgical assessment of 125 adult patients, in which attention/executive function (EpiTrack screening tool) and memory were assessed (cross-sectional study). Of them, 72 patients underwent a second postsurgical evaluation, in which memory was assessed (Study 2). Patients were distributed into groups based on EpiTrack performance and number of ASMs. RESULTS: The interaction between the number of ASMs and the attentional/executive functioning significantly affected presurgical memory, with patients with impaired EpiTrack performance taking three-four ASMs having poorer scores than patients with intact EpiTrack performance taking three-four ASMs (for all, p < .0001). This interaction also affected postsurgical memory changes, with patients with impaired Epitrack performance taking three-four ASMs having higher postsurgical decline than those with intact Epitrack performance taking three-four ASMs (for all, p < .005). No differences were found in patients taking two ASMs. Furthermore, the number of ASMs was associated with presurgical memory performance and postsurgical memory changes only in patients with impaired EpiTrack performance (for all, p < .05). CONCLUSIONS: Our findings underline the utility of EpiTrack, together with the clinical information on the number of prescribed ASMs, to corroborate the impact of polytherapy on memory and to optimize the prediction of postsurgical memory changes.

Vaccination trends in people with HIV infection participanting in the hospital-based survey of patients infected with HIV, 2006-2021.

OBJECTIVE: To assess the trend in hepatitis A, hepatitis B, pneumococcal, tetanus and seasonal influenza vaccination in people with HIV infection and to analyse associated factors. METHODS: The Hospital Survey of Patients with HIV, an annual cross-sectional study conducted on a fixed day (2006-2021), was used. Inpatients and outpatients were included. Trends in vaccination and associated factors were analysed using logistic regression. RESULTS: A total of 8643 participants were included. Vaccination rates increased to 65.3% for hepatitis A, 83.7% for hepatitis B, 49.3% for tetanus, 68.9% for pneumococcal and 74.5% for seasonal influenza in 2021. Factors positively associated with vaccination were older age for pneumococcal and influenza vaccination; higher educational level for hepatitis A and tetanus; living in a closed institutions or prison for tetanus, pneumococcal and influenza; and having acquired HIV through sex between men for hepatitis A, B and pneumococcal. In addition, being on antiretroviral treatment and having a high CD4 count were positively associated with vaccination for all these diseases. Factors inversely associated with vaccination were being older (hepatitis A, B and tetanus), being an immigrant (tetanus and seasonal influenza) and being an injection drug user/ex-user for hepatitis A and B. CONCLUSIONS: Vaccination in people with HIV has increased in the study period. The results are in line with the recommendations in this population, although there is still room to reach the established vaccination indicators.

Evaluación de una intervención comunitaria para incrementar la cobertura vacunal de la gripe en mujeres embarazadas / Evaluation of a community-based intervention to increase influenza vaccination coverage in pregnant women

Objetivo: Conocer el impacto de la intervención educativa realizada sobre los profesionales de una zona básica de salud y su grupo de participación comunitaria, que conforman el grupo intervención (GI), y analizar su repercusión en la cobertura vacunal alcanzada para gripe en el grupo de riesgo (gestantes y puérperas) comparándola con su zona básica vecina, que conforma el grupo control (GC), durante la temporada vacunal 2019/20. Diseño: Estudio cuasiexperimental de intervención comunitaria. Emplazamiento: Dos zonas básicas de salud pertenecientes al departamento de salud Elche-Crevillente, España. Participantes: Gestantes y puérperas de 2 zonas básicas de salud y el grupo de participación comunitaria. Los profesionales de salud directamente relacionados con la campaña vacunal de gripe. Intervenciones: Sesión formativa al GI previa a la campaña de gripe 2019/20. Mediciones principales: Actitudes hacia la vacunación de gripe en profesionales sanitarios mediante el cuestionario validado CAPSVA y la cobertura vacunal de las gestantes y puérperas a través del Registro de Vacunas Nominal y su aceptación a la vacuna en la consulta de la matrona. Resultados: Los datos de cobertura vacunal en gripe registrados en el Registro de Vacunas Nominal para las mujeres gestantes y puérperas fue del 26,4% (n=207) en el GI y del 19,7% (n=144) en el GC (p=0,001), con una razón de incidencia del 1,34, lográndose así un 34% más de vacunación en el GI. La aceptación para la vacunación en las consultas de la matrona también fue elevada, inmunizándose en el GI el 96,5% vs. el 89,0% en el GC, con un RR=1,09 (IC 95% 1,01-1,62).Conclusiones: Estrategias de formación conjunta a profesionales y activos de la comunidad mejoran los resultados de cobertura vacunal.

Objective: To know the impact of the educational intervention carried out on the professionals of a basic health area and their community participation group, which make up the intervention group (IG), and to analyze its repercussion on the vaccination coverage achieved for influenza in the risk group (pregnant and puerperal women) comparing it with its neighboring basic zone, which makes up the control group (CG), during the 2019/20 vaccination season. Design: Quasi-experimental study of community intervention. SiteTwo basic health zones belonging to the Elche-Crevillente health department, Spain. Participants: Pregnant and postpartum women from 2 basic health areas and the community participation group. Health professionals directly related to the flu vaccination campaign. Interventions: Training session for the IG prior to the 2019/20 flu campaign. Main measurements: Attitudes towards influenza vaccination in health professionals through the validated CAPSVA questionnaire and the vaccination coverage of pregnant and postpartum women through the Nominal Vaccine Registry and their acceptance of the vaccine in the midwife's office. Results: The influenza vaccination coverage data recorded in Nominal Vaccine Registry for pregnant and puerperal women was 26.4% (n=207) in the IG and 19.7% (n=144) in the CG (p=0.001), with an incidence ratio of 1.34, thus achieving 34% more vaccination in the IG. Acceptance for vaccination in the midwife's office was also high, with 96.5% immunization in IG vs. 89.0% in CG, with a RR=1.09 (95% CI 1.01-1.62). Conclusions: Joint training strategies for professionals and community assets improve the results of vaccination coverage.(AU)

Novel small molecules inhibit proteotoxicity and inflammation: Mechanistic and therapeutic implications for Alzheimer's Disease, healthspan and lifespan- Aging as a consequence of glycolysis.

Inflammation drives many age-related, especially neurological, diseases, and likely mediates age-related proteotoxicity. For example, dementia due to Alzheimer's Disease (AD), cerebral vascular disease, many other neurodegenerative conditions is increasingly among the most devastating burdens on the American (and world) health system and threatens to bankrupt the American health system as the population ages unless effective treatments are developed. Dementia due to either AD or cerebral vascular disease, and plausibly many other neurodegenerative and even psychiatric conditions, is driven by increased age-related inflammation, which in turn appears to mediate Abeta and related proteotoxic processes. The functional significance of inflammation during aging is also supported by the fact that Humira, which is simply an antibody to the pro-inflammatory cytokine TNF-a, is the best-selling drug in the world by revenue. These observations led us to develop parallel high-throughput screens to discover small molecules which inhibit age-related Abeta proteotoxicity in a C. elegans model of AD AND LPS-induced microglial TNF-a. In the initial screen of 2560 compounds (Microsource Spectrum library) to delay Abeta proteotoxicity, the most protective compounds were, in order, phenylbutyrate, methicillin, and quetiapine, which belong to drug classes (HDAC inhibitors, beta lactam antibiotics, and tricyclic antipsychotics, respectably) already robustly implicated as promising to protect in neurodegenerative diseases, especially AD. RNAi and chemical screens indicated that the protective effects of HDAC inhibitors to reduce Abeta proteotoxicity are mediated by inhibition of HDAC2, also implicated in human AD, dependent on the HAT Creb binding protein (Cbp), which is also required for the protective effects of both dietary restriction and the daf-2 mutation (inactivation of IGF-1 signaling) during aging. In addition to methicillin, several other beta lactam antibiotics also delayed Abeta proteotoxicity and reduced microglial TNF-a. In addition to quetiapine, several other tricyclic antipsychotic drugs also delayed age-related Abeta proteotoxicity and increased microglial TNF-a, leading to the synthesis of a novel congener, GM310, which delays Abeta as well as Huntingtin proteotoxicity, inhibits LPS-induced mouse and human microglial and monocyte TNF-a, is highly concentrated in brain after oral delivery with no apparent toxicity, increases lifespan, and produces molecular responses highly similar to those produced by dietary restriction, including induction of Cbp inhibition of inhibitors of Cbp, and genes promoting a shift away from glycolysis and toward metabolism of alternate (e.g., lipid) substrates. GM310, as well as FDA-approved tricyclic congeners, prevented functional impairments and associated increase in TNF-a in a mouse model of stroke. Robust reduction of glycolysis by GM310 was functionally corroborated by flux analysis, and the glycolytic inhibitor 2-DG inhibited microglial TNF-a and other markers of inflammation, delayed Abeta proteotoxicity, and increased lifespan. These results support the value of phenotypic screens to discover drugs to treat age-related, especially neurological and even psychiatric diseases, including AD and stroke, and to clarify novel mechanisms driving neurodegeneration (e.g., increased microglial glycolysis drives neuroinflammation and subsequent neurotoxicity) suggesting novel treatments (selective inhibitors of microglial glycolysis).

Stress phenotypes in epilepsy: impact on cognitive functioning and quality of life.

Introduction: Drug-resistant epilepsy has been proposed as a chronic stress model. Stress can be measured in terms of chronicity (epilepsy duration) and intensity (comorbidities), with depression and anxiety among the most important comorbidities in epilepsy due to its prevalence and its relationship with cognitive functioning and quality of life. This study aims to establish phenotypes according to how patients face a stressful condition (epilepsy) and examine differences in cognition and quality of life depending on these phenotypes. We hypothesize that there will be an interrelationship between epilepsy duration and negative affectivity, and these variables will influence cognition and quality of life. Methods: 170 patients (82 men and 88 women) underwent a neuropsychological evaluation in which trait anxiety, depression, attention and executive function, verbal and visual memory, language, emotional recognition, and quality of life were assessed. Hierarchical clustering was performed using z-scores for three variables: trait anxiety; depression; and epilepsy duration. Results: Three clusters were found: vulnerable (high negative affectivity and short duration); resilient (moderate negative affectivity and long duration); and low-impact group (low negative affectivity and short duration). Results show that the vulnerable group had poorer cognitive functioning and quality of life than the other groups. Specifically, the vulnerable group had poorer scores than the low-impact group on verbal memory, visual confrontation naming, and quality of life (except seizure worry). Furthermore, resilient patients had better scores than the low-impact group on cognitive flexibility variables, but lower scores on some quality-of-life subscales (i.e., overall quality of life, emotional well-being, and energy). Finally, the vulnerable group had poorer scores than the resilient group in executive functioning, naming, and quality of life. Discussion: These results suggest that dealing with stress in patients with epilepsy is related to cognitive performance and quality of life. These findings underline the relevance of considering comorbidities in epilepsy and may be useful for detecting vulnerable or resilient profiles as risk or protective factors for cognitive and quality of life decline.

Inflammation and lipid metabolism as potential biomarkers of memory impairment across type 2 diabetes mellitus and severe mental disorders.

INTRODUCTION: Neurocognitive impairment is a transdiagnostic feature across several psychiatric and cardiometabolic conditions. The relationship between inflammatory and lipid metabolism biomarkers and memory performance is not fully understood. This study aimed to identify peripheral biomarkers suitable to signal memory decline from a transdiagnostic and longitudinal perspective. METHODS: Peripheral blood biomarkers of inflammation, oxidative stress and lipid metabolism were assessed twice over a 1-year period in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls (HCs). Participants were stratified by memory performance quartiles, taking as a reference their global memory score (GMS) at baseline, into categories of high memory (H; n = 40), medium to high memory (MH; n = 43), medium to low memory (ML; n = 38) and low memory (L; n = 44). Exploratory and confirmatory factorial analysis, mixed one-way analysis of covariance and discriminatory analyses were performed. RESULTS: L group was significantly associated with higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of apolipoprotein A1 (Apo-A1) compared to those from the MH and H groups (p < 0.05; η2p = 0.06-0.09), with small to moderate effect sizes. Moreover, the combination of interleukin-6 (IL-6), TNF-α, c-reactive protein (CRP), Apo-A1 and Apo-B compounded the transdiagnostic model that best discriminated between groups with different degrees of memory impairment (χ2 = 11.9-49.3, p < 0.05-0.0001). CONCLUSIONS: Inflammation and lipid metabolism seem to be associated with memory across T2DM and severe mental illnesses (SMI). A panel of biomarkers may be a useful approach to identify individuals at greater risk of neurocognitive impairment. These findings may have a potential translational utility for early intervention and advance precision medicine in these disorders.

Risk and Protective Factors Associated with Drug Use in Healthcare Professionals: A Systematic Review.

Healthcare professionals are exposed to stressful situations that may favor substance use vulnerability. This systematic review aims to synthesize the risk and protective factors associated with use, abuse, and dependence of alcohol, tobacco, psychoactive drugs, and cannabis in healthcare professionals. Following PRISMA recommendations, a systematic search was performed in PsycINFO, Web of Science, PubMed/MEDLINE, Embase, Scopus, and Cochrane Library. The search yielded 1523 studies, of which 19 were selected. The identified risk factors were demographic factors (i.e. male gender, and single/divorced marital status), psychopathological factors, social factors, positive attitudes toward drugs, unhealthy lifestyle habits, the COVID-19 pandemic, and the coexistence of the use of several substances. The protective factors were demographic factors (i.e. ethnicity and having dependent children), healthy lifestyle habits, and workplace anti-drug policies (i.e. restriction of tobacco use). These findings highlight the need for preventive actions against drug use in healthcare professionals to improve their health and reduce the possible negative impact on their healthcare practice. Knowledge of modifiable risk and protective factors allows their incorporation as components in preventive actions, and non-modifiable factors (e.g. demographic variables) may contribute to the detection of groups of greater vulnerability to propose selective prevention actions in this population.

Health-related quality of life and radiological and functional lung changes of patients with COVID-19 Pneumonia 3 and 10 months after discharge.

BACKGROUND: Few studies have evaluated the long-term impact on health-related quality of life (HRQoL) in patients who have been hospitalized for COVID-19 pneumonia. Specific follow-up should be carried out to detect and treat possible pulmonary abnormalities, and the worsening of HRQoL should be estimated to target necessary resources for care of these patients after acute phase. The objective was to know the impact on HRQoL of patients who have been admitted for COVID-19 pneumonia, and to evaluate the clinical-radiological and functional changes of patients who have overcome COVID-19 pneumonia at 3 and 10 months of follow-up. METHODS: Prospective observational study of patients who required hospitalization for COVID-19 pneumonia between April and December 2020. All patients filled out the EuroQol five-dimension (EQ-5D) questionnaire with the EuroQol Visual Analogue Scale (E-VAS) for self-assessment of health status. Respiratory function tests and chest X-ray were carried out at 3 and 10 months of follow-up. RESULTS: 61 patients were included in the study. The need for ventilatory support was associated with anxiety/depression on the EQ-5D scale, as well as patients admitted to the intensive care unit (ICU). The mean EQ-5D and E-VAS index scores decreased with hospitalization time, the number of days spent in intermediate respiratory care unit (IRCU) and the level of dyspnoea at the beginning of the hospitalization period. Pulmonary sequelae were observed in 25 patients (41%) at 3 months and 17 (27.9%) at 10 months. Patients improve their forced vital capacity (FVC) by 196 ml (p = 0.001) at 10 months as well as 9% in diffusing capacity of lung for carbon monoxide (DLCO) (p = 0.001) at 10 months. DLCO was found to be correlated to lymphopenia and time spent in IRCU. Low FVC values were detected 10 months after discharge for subjects exhibiting high levels of dyspnoea at 3 months after discharge. CONCLUSIONS: Hospitalization for COVID-19 pneumonia affects the HRQoL of patients, with greater anxiety/depression in those who were more serious affected and are younger. A significant percentage of patients present fibrotic abnormalities and lung function impairment at the first and second follow-up after discharge.

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study.

PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.

Gender and organizational culture in the European Union: situation and prospects.

In recent decades, there has been a massive incorporation of women into the labor market. However, the belief that certain jobs or business functions can be performed better by people of one gender than the other has not allowed for widespread changes in the business culture to achieve effective equality between women and men in companies. Examples of this are unequal access to employment, vertical and horizontal segregation in occupations, wage discrimination, problems in reconciling personal and professional life, or difficulties in accessing management positions in companies (glass ceiling). Other determinants of gender inequalities have been long working hours, as well as the presence of employees, characteristic of European business culture. The progress achieved to date began with the incorporation of women into the labor market under unequal conditions that soon called for the need to establish a regulatory framework to try to eradicate them. The legal status of women in Europe has undoubtedly improved as a result of the development of European regulations, which have been binding in the development of business policies in the Member States and have succeeded in modifying the organizational climate through proposals such as the development of Equality Plans or salary audits. Examples of the most recent legislative initiatives of the European Union on equality that affect business practices are Directive 2022/2041/EC on adequate minimum wages in the European Union or Directive 2022/2381/EC on a better gender balance among directors of listed companies. This study attempts to systematize the changes in the legislation on effective equality between men and women in business and to analyze its effect on organizational culture through the information available in the statistics on gender equality-mainly from the European Union-which gather quantitative and qualitative information on the adaptation of business culture to the new legal framework and the overcoming of gender stereotypes that have been guiding business management in the last decade.

[Evaluation of a community-based intervention to increase influenza vaccination coverage in pregnant women]. / Evaluación de una intervención comunitaria para incrementar la cobertura vacunal de la gripe en mujeres embarazadas.

OBJECTIVE: To know the impact of the educational intervention carried out on the professionals of a basic health area and their community participation group, which make up the intervention group (IG), and to analyze its repercussion on the vaccination coverage achieved for influenza in the risk group (pregnant and puerperal women) comparing it with its neighboring basic zone, which makes up the control group (CG), during the 2019/20 vaccination season. DESIGN: Quasi-experimental study of community intervention. SITE: Two basic health zones belonging to the Elche-Crevillente health department, Spain. PARTICIPANTS: Pregnant and postpartum women from 2 basic health areas and the community participation group. Health professionals directly related to the flu vaccination campaign. INTERVENTIONS: Training session for the IG prior to the 2019/20 flu campaign. MAIN MEASUREMENTS: Attitudes towards influenza vaccination in health professionals through the validated CAPSVA questionnaire and the vaccination coverage of pregnant and postpartum women through the Nominal Vaccine Registry and their acceptance of the vaccine in the midwife's office. RESULTS: The influenza vaccination coverage data recorded in Nominal Vaccine Registry for pregnant and puerperal women was 26.4% (n=207) in the IG and 19.7% (n=144) in the CG (p=0.001), with an incidence ratio of 1.34, thus achieving 34% more vaccination in the IG. Acceptance for vaccination in the midwife's office was also high, with 96.5% immunization in IG vs. 89.0% in CG, with a RR=1.09 (95% CI 1.01-1.62). CONCLUSIONS: Joint training strategies for professionals and community assets improve the results of vaccination coverage.