Mortality attributable to secondhand smoke exposure in the autonomous communities of Spain.

INTRODUCTION AND OBJECTIVES: Exposure to secondhand smoke (SHS) causes cardiovascular disease, respiratory disease, and cancer. The aim of this study was to estimate the mortality attributed to SHS in people aged ≥ 35 years in Spain and its autonomous communities (AC) by sex from 2016 to 2021. METHODS: Estimates of SHS-attributable mortality were calculated by applying the prevalence-dependent method where SHS exposure was derived from the adjustment of small-area models and based on the calculation of population-attributed fractions. Sex, age group, AC, and cause of death (ischemic heart disease and lung cancer) were included. The estimates of attributed mortality are presented with their 95% confidence interval (95%CI). Crude and age-standardized rates were estimated for each sex and AC. RESULTS: From 2016 to 2021, SHS exposure caused 4,970 (95%CI, 4,787-5,387) deaths, representing 1.6% of total mortality for ischemic heart disease and lung cancer. The burden of attributed mortality differed widely among the AC, with Andalusia having the highest burden of attributed mortality (crude rate: 46.6 deaths per 100 000 population in men and 17.0/100 000 in women). In all the AC, the main cause of death in both sexes was ischemic heart disease. The highest burden of mortality was observed in nonsmokers. CONCLUSIONS: The burden of SHS-attributable mortality was high and varied geographically. The results of this study should be considered to advance tobacco control legislation in Spain.

Resilience and psychological factors among dentistry students who received face-to-face lectures during the COVID-19 pandemic.

BACKGROUND: This research evaluated whether the relationships between factors of resilience, self-esteem, depression, and anxiety in dental students with changes in teaching and learning methods. We also studied the psychological impact of face-to-face lectures during the COVID-19 pandemic. METHODS: This cross-sectional descriptive study used Google Forms to collect data with the Rosenberg Self-Esteem Scale (RSE), Connor-Davidson Risk Resilience Scale (CD-RISC), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI and BDI-II). An open-ended question was also asked about important learning difficulties. RESULTS: The analysis revealed very high levels of resilience (30.23 ± 5.84), self-esteem in the normal range (29.08 ± 4.03), minimal depression levels (12.32 ± 8.05), and low anxiety levels (17.20 ± 12.41). There were no significant differences between sociodemographic variables ranges in regard to all psychological questionnaires. No high levels of depression and anxiety were found. CONCLUSIONS: The levels were low compared to other studies in which online teaching was used, which is explained by the fact that the students retained adequate resilience and self-esteem thanks to being able to contact teachers and, above all, their own peers.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.

Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease.

Hirschsprung's disease (HSCR) is a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with RET as the major disease-causing gene. However, the pathogenesis of HSCR is still not completely understood. Therefore, we applied a computational approach based on multi-omics network characterization and clustering analysis for HSCR-related gene/miRNA identification and biomarker discovery. Protein-protein interaction (PPI) and miRNA-target interaction (MTI) networks were analyzed by DPClusO and BiClusO, respectively, and finally, the biomarker potential of miRNAs was computationally screened by miRNA-BD. In this study, a total of 55 significant gene-disease modules were identified, allowing us to propose 178 new HSCR candidate genes and two biological pathways. Moreover, we identified 12 key miRNAs with biomarker potential among 137 predicted HSCR-associated miRNAs. Functional analysis of new candidates showed that enrichment terms related to gene ontology (GO) and pathways were associated with HSCR. In conclusion, this approach has allowed us to decipher new clues of the etiopathogenesis of HSCR, although molecular experiments are further needed for clinical validations.

Towards stronger tobacco control policies to curb the smoking epidemic in Spain.

Smoking and exposure to secondhand smoke pose a significant risk to the health of populations. Although this evidence is not new, the commitment of countries to implement laws aimed at controlling consumption and eliminating exposure to secondhand smoke is uneven. Thus, in North America or in Europe, locations like California or Ireland, are pioneers in establishing policies aimed at protecting the population against smoking and secondhand smoke. Identifying measures that have worked would help control this important Public Health problem in other countries that are further behind in tobacco control policies. In Spain, there has been almost 15 years of little political action in legislation oriented to control the tobacco epidemic. If we want to achieve the tobacco endgame, new legislative measures must be implemented. In this paper, we have elucidated tobacco control policies that could be implemented and show how different countries have done so.

Manejo de PICC en el Servicio de Urgencias de un hospital universitario / Use of PICC at the University Hospital Emergency Unit

Para gestionar el capital venoso del paciente con seguridad y responsabilidad es necesario aumentar la calidad de los cuidados proporcionados, unificando y estandarizando los criterios de actuación, basándose siempre en la mejor evidencia científica. Las enfermeras de los Servicios de Urgencias deben aplicar la evidencia en el manejo del catéter venoso central de inserción periférica (PICC), conocer el protocolo aprobado por la Dirección Asistencial de su hospital y, sobre todo, evitar la variabilidad en la actuación, que podría aumentar los riesgos relacionados con la atención sanitaria, así como la desconfianza del paciente. Mantener actualizados los conocimientos y promover la adquisición de habilidades en la práctica clínica es de suma importancia para garantizar cuidados de calidad en el manejo de este tipo de catéteres, debiéndose comprobar periódicamente el grado de cumplimiento de la evidencia recogida en los protocolos existentes en el hospital. Las enfermeras tienen el reto de estar al día en el manejo de los accesos vasculares, y deben responder con seriedad y evidencia a los cuidados que necesitan los pacientes a los que se atienden. En este manuscrito se objetiva la necesidad de formar y capacitar de forma continua a los profesionales para el manejo adecuado del PICC. (AU)

In order to manage the venous resource of the patient safely and with responsibility, it is necessary to increase the quality of care provided, unifying and standardizing performance criteria, always based on the best scientific evidence. Emergency Unit nurses must apply evidence in their use of the peripherally inserted central venous catheter (PICC), they must know the protocol approved by the Patient Care Management in their hospital and, most of all, must avoid variability of action, which could increase the risks associated with healthcare as well as mistrust by patients. It is extremely important to keep an updated knowledge and to promote the acquisition of clinical practice skills, in order to guarantee quality care in the use of this type of catheters; the level of compliance of the evidence collected in the hospital protocols must be confirmed periodically. Nurses face the challenge of being updated in the management of vascular accesses, and must give response with seriousness and evidence to the care needed by their patients. This manuscript sets out objectively the need for continuous training and qualification for professionals regarding the adequate use of PICC. (AU)

Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

BACKGROUND: APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear. METHODS: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated. RESULTS: In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of low-density lipoprotein (LDL)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect. CONCLUSIONS: This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife. REGISTRATION: URL: https://www.clinicaltrials.gov: NCT01410318.

Oral anticoagulants: A plausible new treatment for Alzheimer's disease?

Alzheimer's disease (AD) and cardiovascular disease (CVD) are strongly associated. Both are multifactorial disorders with long asymptomatic phases and similar risk factors. Indeed, CVD signatures such as cerebral microbleeds, micro-infarcts, atherosclerosis, cerebral amyloid angiopathy and a procoagulant state are highly associated with AD. However, AD and CVD co-development and the molecular mechanisms underlying such associations are not understood. Here, we review the evidence regarding the vascular component of AD and clinical studies using anticoagulants that specifically evaluated the development of AD and other dementias. Most studies reported a markedly decreased incidence of composite dementia in anticoagulated patients with atrial fibrillation, with the highest benefit for direct oral anticoagulants. However, sub-analyses by differential dementia diagnosis were scarce and inconclusive. We finally discuss whether anticoagulation could be a plausible preventive/therapeutic approach for AD and, if so, which would be the best drug and strategy to maximize clinical benefit and minimize potential risks. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4+ T cells in giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4+ T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4+ T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.799 circulating CD4+ T cells from eight GCA patients in two different clinical states, active and in remission, and eight healthy controls. Our results revealed an expansion of cytotoxic CD4+ T lymphocytes (CTLs) in active GCA patients, which expressed higher levels of cytotoxic and chemotactic genes when compared to patients in remission and controls. Accordingly, differentially expressed genes in CTLs of active patients were enriched in pathways related to granzyme-mediated apoptosis, inflammation, and the recruitment of different immune cells, suggesting a role of this cell type in the inflammatory and vascular remodelling processes occurring in GCA. CTLs also exhibited a higher clonal expansion in active patients with respect to those in remission. Drug repurposing analysis prioritized maraviroc, which targeted CTLs, as potentially repositionable for this vasculitis. In addition, effector regulatory T cells (Tregs) were decreased in GCA and showed lower expression of genes involved in their suppressive activity. These findings provide further insights into the pathogenic role of CD4+ T cells in GCA and suggest targeting CTLs as a potential therapeutic option.

Self-expanding TAVI using the cusp overlap technique versus the traditional technique: electrocardiogram changes and 1-year cardiovascular outcomes.

INTRODUCTION AND OBJECTIVES: Transcatheter aortic valve implantation (TAVI) using the cusp overlap technique (COT) has shown a lower pacemaker implantation rate at 30 days. The objective of this study was to compare electrocardiogram changes and clinical outcomes between COT and the traditional technique (TT) at 1 year of follow-up. METHODS: Observational, retrospective, nonrandomized study of consecutive patients undergoing TAVI between January 2015 and January 2021. Patients were matched using a propensity score and the TT was compared with COT. The primary endpoints were electrocardiogram changes and a combined endpoint including pacemaker implantation, hospitalization, or cardiovascular death at 1 year. RESULTS: We included 254 patients. After propensity score matching, 184 patients (92 per group) remained. There were no statistically significant differences in baseline characteristics. At 1 year, COT patients showed a significant reduction in new onset left bundle branch block (49% vs 27%, P=.002) and less P wave (13.1±21.0 msec vs 5.47±12.5 msec; P=.003) and QRS prolongation (29.77±27.0 msec vs 16.38±25.4 msec, P <.001). COT was associated with a significant reduction in the occurrence of the primary endpoint (SHR, 0.39 [IC95%, 0.21-0.76]; P=.005). CONCLUSIONS: At 1 year of follow-up, COT reduced the incidence of new onset left bundle branch block and diminished QRS and P wave widening compared with the TT. COT was also associated with a statistically significant reduction in the occurrence of the combined primary cardiovascular endpoint.

Lymphoid interstitial pneumonia in a patient with systemic lupus erythematosus: Case report and literature review.

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

BACKGROUND: Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. METHODS: From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. RESULTS: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. CONCLUSIONS: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Implementation feasibility of animal-assisted therapy in a pediatric intensive care unit: effectiveness on reduction of pain, fear, and anxiety.

Animal-assisted therapies are an innovative strategy within health care humanization initiatives, and they could play a role in the reduction of pain or anxiety. The main objective of this work was to evaluate the feasibility of implementing animal-assisted therapy in a pediatric intensive care unit and its effectiveness for the reduction of pain, fear, and anxiety. A prospective, quasi-experimental study of animal-assisted therapy was designed in the pediatric intensive care unit of the Hospital Universitario 12 de Octubre of Madrid, from January 2019 to December 2019. The study sample included patients who had been admitted to the unit and were over 3 years old. Satisfaction surveys were collected from the patients, family, and health personnel involved. Physiological variables and the level of pain (visual analog scale or Wong-Baker scale), fear (Child Medical Fear Scale), and anxiety (modified Yale Preoperatory Anxiety Scale) were evaluated before and after each session. Any existence of adverse events was recorded. A total of 74 therapy sessions were performed on 61 patients. All sessions were completed without any adverse effects. A total of 164 surveys were collected, providing an overall project rating of 9.69 out of a possible 10. The survey comments were found to be positive in most cases. No differences were found in the physiological variables measured before and after each session. There was a statistically significant decrease in pain, fear, and anxiety levels (p < 0.01).   Conclusion: The implementation of an animal-assisted therapy project in a pediatric intensive care unit is feasible and safe and has a high degree of acceptance among both participants and healthcare staff. Animal-assisted therapy is effective for the reduction of pain, fear, and anxiety, and therefore, it could be considered an adjunct to non-pharmacological therapy. What is Known: • Animal assisted therapies (AAT) are an innovative strategy that could be beneficial to help pediatrics patients cope with admission difficulties and could even play a role in reducing pain, anxiety and/or delirium. • To date there are not studies to analyze the effectiveness of AAT in the field of Pediatric Intesive Care. What is New: • Our study confirms the feasibility and effectiveness of the implementation of an AAT in the field of Pediatric Intensive Care with a high degree of acceptance by participants, caregivers and healthcare personnel. • AAT demonstrated a reduction in pain, fear and anxiety in pediatrics patients admitted to Pediatric Intensive Care Unit.

Modelling Polyphenol Extraction through Ultrasound-Assisted Extraction by Machine Learning in Olea europaea Leaves.

The study of the phenolic compounds present in olive leaves (Olea europaea) is of great interest due to their health benefits. In this research, different machine learning algorithms such as RF, SVM, and ANN, with temperature, time, and volume as input variables, were developed to model the extract yield and the total phenolic content (TPC) from experimental data reported in the literature. In terms of extract yield, the neural network-based ANNZ-L model presents the lowest root mean square error (RMSE) value in the validation phase (9.44 mg/g DL), which corresponds with a mean absolute percentage error (MAPE) of 3.7%. On the other hand, the best model to determine the TPC value was the neural network-based model ANNR, with an RMSE of 0.89 mg GAE/g DL in the validation phase (MAPE of 2.9%). Both models obtain, for the test phase, MAPE values of 4.9 and 3.5%, respectively. This affirms that ANN models would be good modelling tools to determine the extract yield and TPC value of the ultrasound-assisted extraction (UAE) process of olive leaves under different temperatures, times, and solvents.

Identification of Reference Genes for Precise Expression Analysis during Germination in Chenopodium quinoa Seeds under Salt Stress.

Chenopodium quinoa Willd. (quinoa), a member of the Amaranthaceae family, is an allotetraploid annual plant, endemic to South America. The plant of C. quinoa presents significant ecological plasticity with exceptional adaptability to several environmental stresses, including salinity. The resilience of quinoa to several abiotic stresses, as well as its nutritional attributes, have led to significant shifts in quinoa cultivation worldwide over the past century. This work first defines germination sensu stricto in quinoa where the breakage of the pericarp and the testa is followed by endosperm rupture (ER). Transcriptomic changes in early seed germination stages lead to unstable expression levels in commonly used reference genes that are typically stable in vegetative tissues. Noteworthy, no suitable reference genes have been previously identified specifically for quinoa seed germination under salt stress conditions. This work aims to identify these genes as a prerequisite step for normalizing qPCR data. To this end, germinating seeds from UDEC2 and UDEC4 accessions, with different tolerance to salt, have been analyzed under conditions of absence (0 mM NaCl) and in the presence (250 mM NaCl) of sodium chloride. Based on the relevant literature, six candidate reference genes, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Monensin sensitivity1 (MON1), Polypyrimidine tract-binding protein (PTB), Actin-7 (ACT7), Ubiquitin-conjugating enzyme (UBC), and 18S ribosomal RNA (18S), were selected and assessed for stability using the RefFinder Tool encompassing the statistical algorithms geNorm, NormFinder, BestKeeper, and ΔCt in the evaluation. The data presented support the suitability of CqACT7 and CqUBC as reference genes for normalizing gene expression during seed germination under salinity stress. These recommended reference genes can be valuable tools for consistent qPCR studies on quinoa seeds.

Effectiveness of child sexual abuse prevention programs on knowledge acquisition: A meta-analytical study.

BACKGROUND: Child sexual abuse (CSA) is a type of maltreatment considered a global health problem. CSA is a traumatic experience with important consequences for the victim's health. It is essential to report the effectiveness of CSA prevention programs to offer society useful tools to combat this abuse. OBJECTIVE: We aimed to study the effectiveness of CSA prevention programs on the knowledge acquisition based on comparing pre- and post-treatment changes, and also if their effectiveness is related to program-related and methodological variables. PARTICIPANTS AND SETTINGS: Standardised mean change (with studies that report pre-post program measures) of the effectiveness of CSA prevention programs published between 2014 and 2021 was carried out. METHODS: The general effectiveness of these programs and whether the results were influenced by program-related variables (the duration, the target population, participants' age, or the type of intervention) or by methodology-related factors (the agent who taught them, the geographical area where they were carried out or the way the programs were evaluated) were analysed. A total of 43 samples analysing knowledge about CSA as a dependent variable were included. RESULTS: The results reported a combined effect size considered large (dMR = -0.96, 95 % CI [-1.10, -0.82], p < .001). High inter-study heterogeneity was observed in the meta-analysis, although only the geographic area where the studies were conducted appears as a significant moderator. CONCLUSIONS: In conclusion, the prevention programs included in this analysis significantly improved the participants' knowledge acquisition.

Variant Classification for Pompe disease; ACMG/AMP specifications from the ClinGen Lysosomal Diseases Variant Curation Expert Panel.

Accurate determination of the clinical significance of genetic variants is critical to the integration of genomics in medicine. To facilitate this process, the NIH-funded Clinical Genome Resource (ClinGen) has assembled Variant Curation Expert Panels (VCEPs), groups of experts and biocurators which provide gene- and disease- specifications to the American College of Medical Genetics & Genomics and Association for Molecular Pathology's (ACMG/AMP) variation classification guidelines. With the goal of classifying the clinical significance of GAA variants in Pompe disease (Glycogen storage disease, type II), the ClinGen Lysosomal Diseases (LD) VCEP has specified the ACMG/AMP criteria for GAA. Variant classification can play an important role in confirming the diagnosis of Pompe disease as well as in the identification of carriers. Furthermore, since the inclusion of Pompe disease on the Recommended Uniform Screening Panel (RUSP) for newborns in the USA in 2015, the addition of molecular genetic testing has become an important component in the interpretation of newborn screening results, particularly for asymptomatic individuals. To date, the LD VCEP has submitted classifications and supporting data on 243 GAA variants to public databases, specifically ClinVar and the ClinGen Evidence Repository. Here, we describe the ACMG/AMP criteria specification process for GAA, an update of the GAA-specific variant classification guidelines, and comparison of the ClinGen LD VCEP's GAA variant classifications with variant classifications submitted to ClinVar. The LD VCEP has added to the publicly available knowledge on the pathogenicity of variants in GAA by increasing the number of expert-curated GAA variants present in ClinVar, and aids in resolving conflicting classifications and variants of uncertain clinical significance.

Sex-related differences in the associations between diurnal cortisol pattern and social and emotional loneliness in older adults.

Introduction: Loneliness is a distressful feeling that can affect mental and physical health, particularly among older adults. Cortisol, the primary hormone of the Hypothalamic-Pituitary-Adrenal axis (HPA-axis), may act as a biological transducer through which loneliness affects health. While most previous studies have evaluated the association between loneliness, as a unidimensional construct, and diurnal cortisol pattern, no research has examined this relationship discriminating between social and emotional loneliness in older adults. As sex differences in the negative mental health outcomes of loneliness have been reported, we also investigated whether diurnal cortisol indices and loneliness associations occur in a sex-specific manner. Methods: We analyzed the diurnal cortisol- pattern in 142 community-dwelling, non-depressed, Caucasian older adults (55,6% female) aged 60-90. Social and emotional (family and romantic) loneliness scores were assessed using the Spanish version of the Social and Emotional Loneliness Scale for Adults (SELSA). Five salivary cortisol samples were used to capture key features of the diurnal cortisol pattern, including: awakening and bedtime cortisol levels, awakening response (CAR), post-awakening cortisol output (post-awakening cortisol [i.e., the area under the curve with reference to the ground: AUCG]), total diurnal cortisol release (AUCG), and diurnal cortisol slope (DCS). Results: After controlling for sociodemographic variables, the hierarchical linear multiple regression analyses revealed that in male older adults, higher scores on social and family loneliness were associated with elevated awakening cortisol levels, total diurnal cortisol output, and a steeper diurnal cortisol slope (DCS). However, these associations were not observed in female older adults. In addition, feelings of romantic loneliness were positively associated with bedtime cortisol levels and AUCG in older males. Multilevel growth curve modeling showed that experiencing more social and emotional loneliness predicted higher diurnal cortisol output throughout the day in older male adults. Discussion: The presence of sex differences in the relationship between cortisol indices and loneliness among older adults holds particular significance for diagnostic and screening procedures. Combining loneliness scales as screening tools with diurnal cortisol measures has the potential to be an effective and cost-efficient approach in identifying higher-risk individuals at early stages.

Effects of Myofascial Induction Therapy on Ankle Range of Motion and Pressure Pain Threshold in Trigger Points of the Gastrocnemius-A Clinical Trial.

BACKGROUND: The myofascial induction technique (MIT) has been shown to increase shoulder range of motion (ROM) in breast cancer survivors and decrease pain pressure threshold over the radial nerve in patients with epicondylalgia. To the authors' best knowledge, no study on trigger points and MIT has been published to date. The effect on ROM of latent trigger points is also unknown. METHODS: A total of 20 twins with one latent trigger point of the gastrocnemius muscle were evaluated pre- and post-MIT in the calf. We measured static footprint variables in a pre-post study. RESULTS: We found differences in PPT (p = 0.001) and no differences in ROM with knee flexed (p = 0.420) or stretched (p = 0.069). CONCLUSIONS: After Calf MIT, latent myofascial trigger points improve PPT but no change in ankle dorsiflexion with knee bent or knee flexed were found in non-restriction healthy subjects.