Inhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.

The upregulation of Orai1 and subsequent store-operated Ca2+ entry (SOCE) has been associated with adverse cardiac remodeling and heart failure (HF). However, the mechanism underlying Orai1 upregulation and its role in myocardial infarction remains unclear. Our study investigated the role of Orai1 in activating adenylyl cyclase 8 (AC8) and cyclic AMP (cAMP) response element-binding protein (CREB), as well as its contribution to cardiac dysfunction induced by ischemia and reperfusion (I/R). We found that I/R evoked an increase in the expression of Orai1 and AC8 in rats' hearts, resulting in a substantial rise in diastolic Ca2+ concentration ([Ca2+]i), and reduced ventricular contractions. The expression of Orai1 and AC8 was also increased in ventricular biopsies of post-ischemic HF patients. Mechanistically, we demonstrate that I/R activation of Orai1 stimulated AC8, which produced cAMP and phosphorylated CREB. Subsequently, p-CREB activated the ORAI1 promoter, resulting in Orai1 upregulation and SOCE exacerbation. Intramyocardial administration of AAV9 carrying AC8 short hairpin RNA decreased the expression of AC8, Orai1 and CREB, which restored diastolic [Ca2+]i and improved cardiac contraction. Therefore, our data suggests that the axis composed by Orai1/AC8/CREB plays a critical role in I/R-induced cardiac dysfunction, representing a potential new therapeutic target to limit the progression of the disease toward HF.

Chest Decompressions - The Driver of CPR Efficacy: Exploring the Relationship Between Compression Rate, Depth, Recoil Velocity, and End-Tidal CO2.

OBJECTIVE: Cardiopulmonary arrest survival is dependent on optimization of perfusion via high quality cardiopulmonary resuscitation (CPR), defined by a complex dynamic between rate, depth, and recoil velocity. Here we explore the interaction between these metrics and create a model that explores the impact of these variables on compression efficacy. METHODS: This study was performed in a large urban/suburban fire-based emergency medical services (EMS) system over a nine-month period from 2019 to 2020. Manual chest compression parameters [rate/depth/recoil velocity] from a cohort of out-of-hospital cardiac arrest (OOHCA) victims were abstracted from monitor defibrillators (ZOLL X-series) and end-tidal carbon dioxide (ETCO2) from sensors. The mean values of these parameters were modeled against each other using multiple regression and structural equation modeling with ETCO2 as a dependent variable. RESULTS: Data from a total of 335 patients were analyzed. Strong linear relationships were observed between compression depth/recoil velocity (r = .87, p < .001), ETCO2/depth (r = .23, p < .001) and ETCO2/recoil velocity (r = .61, p < .001). Parabolic relationships were observed between rate/depth (r = .39, p < .001), rate/recoil velocity (r = .26, p < .001), and ETCO2/rate (r = .20, p = .003). Rate, depth, and recoil velocity were modeled as independent variables and ETCO2 as a dependent variable with excellence model performance suggesting the primary driver of stroke volume to be recoil velocity rather than compression depth. CONCLUSIONS: We used manual CPR metrics from out of hospital cardiac arrests to model the relationship between CPR metrics. These results consistently support the importance of chest recoil on CPR hemodynamics, suggesting that guidelines for optimal CPR should emphasize the importance of maximum chest recoil.

Depressive-Like Effects of Foreclosing: A Cross-Sectional Study of Hair Cortisol Concentration.

INTRODUCTION: Foreclosing and home eviction have been associated with various negative health outcomes, probably due to exposure to such stressful circumstance, but there is no evidence about foreclosure and home eviction to elicit cortisol responses. METHODS: Participants who recently had received a court eviction notice were compared to subjects suffering a depressive disorder and to healthy controls in terms of hair cortisol concentrations. RESULTS: Subjects under the stressful circumstance of foreclosure and patients with depression showed comparable concentrations in most of the hair segments while healthy subjects displayed the lowest levels of cortisol. CONCLUSION: The findings show that foreclosure and home eviction are associated with increased cumulative hair cortisol and with depressive-like symptoms. Foreclosing procedures yielded to maintain high levels of cortisol which may increase the risk to develop major depression.

That kid is a grasshopper! Metaphor development from 3 to 9 years of age.

Two major trends on children's skills to comprehend metaphors have governed the literature on the subject: the literal stage hypothesis vs. the early birds hypothesis (Falkum, 2022). We aim to contribute to this debate by testing children's capability to comprehend novel metaphors ('X is a Y') in Spanish with a child-friendly, picture selection task, while also tracking their gaze. Further, given recent findings on the development of metonymy comprehension suggesting a U-shaped developmental curve for this phenomenon (Köder & Falkum, 2020), we aimed to determine the shape of the developmental trajectory of novel metaphor comprehension, and to explore how both types of data (picture selection and gaze behavior) relate to each other. Our results suggest a linear developmental trajectory with 6-year-olds significantly succeeding in picture selection and consistently looking at the metaphorical target even after question onset.

Detecting, Quantifying, and Isolating Monkeypox Virus in Suspected Cases, Spain.

When a monkeypox virus outbreak began in several parts of the world in May 2022, timely and accurate diagnosis became mandatory. In our laboratory, a real-time quantitative PCR was designed and evaluated in several patient samples and compared with isolation results. Genomic viral load was related to virus viability.

Usefulness of SPISE Index for Screening and Detection of Early Stages of Insulin Resistance among Chilean Young Adults.

BACKGROUND: As the gold standard test to quantify insulin resistance (IR) involves intravenous insulin loading and repeated blood glucose monitoring, many indexes have been developed for IR assessment for convenience. OBJECTIVE: The objective of this study was to evaluate the agreement of the Single-Point Insulin Sensitivity Estimator (SPISE) by comparing it with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying IR. METHOD: Data came from the ongoing LIMACHE BIRTH COHORT. 1,948 individuals (aged 22-28 years) were studied. We performed an agreement plot called a Bangdiwala's Observer Agreement to evaluate patterns in departures from agreement in ordinal categorical variables. RESULTS: According to the Bangdiwala-Weighted statistics, we found that the agreement between both indexes was 0.14; this value would be considered a slight agreement. Thus, we found bias in the marginal distributions, and we noticed that the SPISE has a bias toward the central quintiles of the index. CONCLUSIONS: The identification of IR in young adult individuals by the SPISE index has slight agreement with HOMA-IR. Therefore, caution would be taken when considering SPISE index among young Chilean adults.

Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project).

BACKGROUND: Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. OBJECTIVE: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. METHODS: A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. RESULTS: Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4-5, and stages GDS 6-7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). CONCLUSIONS: The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.

School professionals' knowledge about pediatric traumatic brain injury: an international study.

OBJECTIVE: To determine Spanish-speaking school professionals' level of knowledge and attitudes regarding pediatric TBI. METHODS: School professionals(n = 2,238) from 19 countries completed an online-survey regarding their training, knowledge and misconceptions, attitudes and perceptions about TBI. RESULTS: Of the full sample 75% (n = 1689) knew what TBI was, though only 18% (n = 350) reported having experience with a student with TBI. Only 7.7% (n = 143) and 3% (n = 55) of participants could identify all of the common short- and long-term TBI sequelae, respectively. Special education professionals, those with experience with a student with TBI, and those who had received training regarding TBI showed greater knowledge in these areas. Although participants showed high levels of knowledge in 6/24 misconceptions of TBI, they endorsed others. Group, sex, experience with students with TBI, training in TBI, and number of years working were significantly linked to some misconceptions about TBI; however, the effect sizes were small. CONCLUSION: The knowledge and experience that Spanish-speaking school professionals have regarding childhood TBI are minimal. It is therefore critical that these professionals receive a more comprehensive education during their academic training and the practice of their profession about TBI.

Ultra-processed food consumption and the incidence of obesity in two cohorts of Latin-American young children: A longitudinal study.

PURPOSE: We evaluated the potential associations between the consumption of ultra-processed food (UPF) and the incidence of obesity among Uruguayan and Brazilian preschoolers. DESIGN AND METHODS: We conducted a longitudinal analysis using data from preschool children from Uruguay and Brazil. The "Health, child development and nutritional survey" (ENDIS) was conducted in Uruguay in 2013-2014 and 2015-2016. The Brazilian survey (Pelotas 2015 Birth Cohort) has measures from 2017 and 2019. The main outcome measure was obesity defined as body mass index (BMI) for age and sex ≥ +3 z-scores. The score of UPF consumption was the main exposure measured. Multilevel crude and adjusted Poisson regressions were performed to estimate risk ratios and the respective 95% Confidence Intervals (95% CI). RESULTS: The overall incidence of obesity in this group of young Latin-American children with a mean age of 48 months was 4.1%. We observed a relationship between UPF and obesity with statistical significance (RR: 1.10 (95% CI, 1.02-1.18). Adjustment for weight at birth, age, sex, breastfeeding, country, and time between waves resulted in a similar relationship but lack of statistical significance. CONCLUSIONS: Whilst in this study we did not find strong evidence of an association between the incidence of obesity and the intake at baseline and currently of UPF, results suggest that higher UPF consumption is more favorable than reduced consumption for the development of obesity. PRACTICE IMPLICATIONS: The present study reinforces the importance of nutrition education and more effective public policies for promoting healthier food choices in early childhood.

Emergency Management Strategies and Antimicrobial Considerations for Nonmammalian Marine Vertebrate Penetrating Trauma in North America, the Caribbean, and Hawaii: A Review Article.

There are numerous emergency department visits in the United States for all types of marine animal injuries each year. These injuries may result in significant morbidity or mortality if not managed appropriately. Accurate identification of the offending species, thorough wound hygiene, and judicious use of antibiotics are important for preventing infections. This review aims to describe management strategies and antimicrobial considerations for nonmammalian marine vertebrate penetrating trauma in North America, the Caribbean, and Hawaii. A literature search was performed to identify studies on this subject. This literature consisted of clinical case reports and case series. Reports extracted included those on sharks, barracuda, eels, catfish, stingrays, lionfish, stonefish, and scorpionfish. The majority of reported trauma occurred to beachgoers, fishermen, or commercial aquarium employees who routinely handle these animals. Injury patterns depended on the species but most commonly affected the lower extremities. Infections were seen from saltwater bacteria, human skin flora, or marine animal oral flora. After thorough wound irrigation and exploration, most authors recommended prophylactic antimicrobials to cover Vibrio species, in addition to other gram-negative and gram-positive species. The literature is notable for the lack of controlled studies. Some authors recommended radiographic and/or ultrasonographic imaging to identify retained foreign bodies, such as spines, sand, or teeth.

Early detection of ocular lesions in critically ill children: Testing an ocular assessment scale.

OBJECTIVE: There is scarcity of data on the incidence and factors associated with the occurrence of ocular lesions in critically ill children. The objective was to test the applicability and utility of an ocular assessment scale and to identify risk factors of ocular lesions. DESIGN: Prospective observational study. SETTING: A tertiary care medical-surgical Paediatric Intensive Care Unit. SAMPLE: 194 children without previous ocular disease who stayed in the Paediatric Intensive Care Unit for more than 48 h. INTERVENTIONS: An ocular lesions risk scale was designed including risk factors lagophthalmos, eye dryness, conjunctival hyperemia, slow blinking, intubation, sedation, relaxation, face mask and hemodynamic instability. Patients were classified as high-, medium-, and low-risk patients. Corneal lesions were examined by fluorescein staining according to their risk and were confirmed by an ophthalmologist. RESULTS: 76 patients were examined with fluorescein staining. Thirty-two ocular lesions were detected by nursing staff, 26 confirmed by the ophthalmologist. 53.6% of the high-risk patients developed a corneal lesion. Univariate analysis revealed an association between ocular damage and all factors included in the scale, except for face mask. In the multivariate analysis, ocular lesions were associated with lagophthalmos, hyperemia, invasive mechanical ventilation and inotropic support. CONCLUSIONS: The scale was useful to detect corneal lesions in critically ill children. The identification of risk factors will enable the development of measures to reduce the incidence of ocular lesions. RELEVANCE FOR CLINICAL PRACTICE: A new, non-validated scale allowed staff to detect eye injuries, study this problem and improve future prevention.

Business groups' internal labour markets and SME labour productivity.

Labour market regulation constrains small and medium-sized enterprises' (SMEs) ability to minimize redundant labour. However, it is often neglected that many SMEs might circumvent these constraints by accessing a business group's internal labour market (ILM). In this study, we analyse whether SMEs with ILM access-i.e., with an increasing number of sister group companies in the same subnational region-industry-enjoy a labour productivity premium and whether this potential productivity premium depends on the bargaining power of labour. Because intra-group reallocation of redundant personnel often involves substantial changes in employment conditions, we argue that the value of ILM access might be reduced when the bargaining power of workers is high as they can oppose the reallocation or demand significant compensation. Using a panel of 119,801 European SMEs during 2011-2019 (639,675 firm-year observations), we find that SMEs with ILM access show relatively higher labour productivity. Further, our findings suggest that this productivity premium is higher in those contexts associated with lower labour bargaining power. Supplementary Information: The online version contains supplementary material available at 10.1007/s11187-023-00780-4.

Effectiveness of a group educational intervention - prolact - in primary care to promote exclusive breastfeeding: a cluster randomized clinical trial.

BACKGROUND: The rates of exclusive breastfeeding at 6 months in Spain are far from recommended by the World Health Organization, which is 50% by 2025. Evidence of the effectiveness of group interventions in late postpartum is limited. The objective of this study was to evaluate the effectiveness of the PROLACT group educational intervention for increasing the proportion of mother-child dyads with exclusive breastfeeding at 6 months compared to the usual practice in primary care. METHOD: Multicentre cluster randomized clinical trial. A total of 434 mother-child dyads who breastfed exclusively in the first 4 weeks of the children's life and agreed to participate were included. The main outcome was exclusive breastfeeding at 6 months. Secondary variables were type of breastfeeding, reasons for abandonment, degree of adherence and satisfaction with the intervention. To study the effectiveness, the difference in the proportions of dyads with exclusive breastfeeding at 6 months was calculated, and the relative risk (RR) and number needed to treat (NNT) were calculated with their 95% CIs. To study the factors associated with the maintenance of exclusive breastfeeding at 6 months, a multilevel logistic regression model was fitted. All analyses were performed to intention to treat. RESULTS: The percentage of dyads with exclusive breastfeeding at 6 months was 22.4% in the intervention group and 8.8% in the control group. PROLACT intervention obtained an RR =2.53 (95% CI: 1.54-4.15) and an NNT = 7 (95%CI: 5-14). The factors associated with exclusive breastfeeding at 6 months were the PROLACT intervention, OR = 3.51 (95%CI: 1.55-7.93); age > 39 years, OR = 2.79 (95%CI: 1.02-7.6); previous breastfeeding experience, OR = 2.61 (95%CI: 1.29-5.29); income between 500 and 833.33 €, OR = 3.52 (95%CI 1.47-8.47).); planning to start work before the infant was 6 months old, OR = 0.35 (0.19-0.63) . CONCLUSIONS: The PROLACT intervention in primary care is more effective than the usual practice for maintaining exclusive breastfeeding at 6 months, and can therefore be considered evidence-based practice for implementation in standard practice. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov under code number NCT01869920 (03/06/2013).

Neuropsychiatric symptoms and subsyndromes in patients with different stages of dementia in primary care follow-up (NeDEM project): a cross-sectional study.

BACKGROUND: The objective was to describe the prevalence and intensity of neuropsychiatric symptoms (NPSs) isolated and grouped into subsyndromes in patients with dementia in primary care (PC) to analyse their distribution based on stages of dementia and the relationship between them and the intensity of symptoms. METHODS: Design: Cross-sectional study. SETTING AND POPULATION: Patients with dementia, not institutionalized, in a PC follow-up. VARIABLES: Sociodemographic and clinical variables. Assessment instruments: The frequency and intensity of NPSs were measured with the Neuropsychiatric Inventory (NPI), and the stages of dementia with the Global Deterioration Scale (GDS). STATISTICAL ANALYSIS: The number of NPSs per patient, the mean NPI value, and the prevalence and intensity of NPSs isolated and grouped into subsyndromes were calculated, as were their 95% confidence intervals (CIs). The analyses were performed on an overall basis and by GDS scores. To analyse the association between the NPI and GDS scores, multivariate analysis was performed with a generalized linear model. RESULTS: Overall, 98.4% (95% CI 94.5;99.8) of the patients presented some type of NPS, with an average of five symptoms per patient. The most frequent symptoms were apathy [69.8% (95% CI 61.1;77.5)], agitation [55.8% (95% CI 46.8;64.5)] and irritability [48.8% (95% CI 39.9;57.8)]. The more intense NPSs were apathy [NPI 3.2 (95% CI 2.5;3.8)] and agitation [NPI 3.2 (95% CI 2.5;4.0)]. For subsyndromes, hyperactivity predominated [86.0% (95% CI 78.8;91.5)], followed by apathy [77.5% (95% CI 69.3;84.4]). By phase of dementia, the most common isolated symptom was apathy (60.7-75.0%). Affective symptoms and irritability predominated in the initial stages, and psychotic symptoms predominated in advanced stages. The mean NPI score was 24.9 (95% CI 21.5;28.4) and increased from 15.6 (95% CI 8.2;23.1) for GDS 3 to 28.9 (95% CI 12.6;45.1) for GDS 7. Patients with in the most advanced stages of dementia presented an NPI score 7.6 (95% CI 6.8;8.3) points higher than the score for mild dementia with adjustment for the other variables. CONCLUSIONS: A high prevalence of NPSs was found among patients with dementia treated in PC. Symptoms change and increase in intensity as the disease progresses. Scales such as the NPI allow these symptoms to be identified, which may facilitate more stage-appropriate management.

Effectiveness of a game-based educational strategy e-EDUCAGUIA for implementing antimicrobial clinical practice guidelines in family medicine residents in Spain: a randomized clinical trial by cluster.

BACKGROUND: Clinical practice guidelines (CPGs) have teaching potential for health professionals in training clinical reasoning and decision-making, although their use is limited. The objective was to evaluate the effectiveness of a game-based educational strategy e-EDUCAGUIA using simulated clinical scenarios to implement an antimicrobial therapy GPC compared to the usual dissemination strategies to improve the knowledge and skills on decision-making of family medicine residents. Additionally, adherence to e-EDUCAGUIA strategy was assessed. METHODS: A multicentre pragmatic cluster-randomized clinical trial was conducted involving seven Teaching Units (TUs) of family medicine in Spain. TUs were randomly allocated to implement an antimicrobial therapy guideline with e-EDUCAGUIA strategy ( intervention) or passive dissemination of the guideline (control). The primary outcome was the differences in means between groups in the score test evaluated knowledge and skills on decision-making at 1 month post intervention. Analysis was made by intention-to-treat and per-protocol analysis. Secondary outcomes were the differences in mean change intrasubject (from the baseline to the 1-month) in the test score, and educational game adherence and usability. Factors associated were analysed using general linear models. Standard errors were constructed using robust methods. RESULTS: Two hundred two family medicine residents participated (104 intervention group vs 98 control group). 100 medicine residents performed the post-test at 1 month (45 intervention group vs 55 control group), The between-group difference for the mean test score at 1 month was 11 ( 8.67 to 13.32) and between change intrasubject was 11,9 ( 95% CI 5,9 to 17,9). The effect sizes were 0.88 and 0.75 respectively. In multivariate analysis, for each additional evidence-based medicine training hour there was an increase of 0.28 points (95% CI 0.15-0.42) in primary outcome and in the change intrasubject each year of increase in age was associated with an improvement of 0.37 points and being a woman was associated with a 6.10-point reduction. 48 of the 104 subjects in the intervention group (46.2%, 95% CI: 36.5-55.8%) used the games during the month of the study. Only a greater number of evidence-based medicine training hours was associated with greater adherence to the educational game ( OR 1.11; CI 95% 1.02-1.21). CONCLUSIONS: The game-based educational strategy e-EDUCAGUIA shows positive effects on the knowledge and skills on decision making about antimicrobial therapy for clinical decision-making in family medicin residents in the short term, but the dropout was high and results should be interpreted with caution. Adherence to educational games in the absence of specific incentives is moderate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210442 . Registered 6 August 2014.

Health-related quality of life in caregivers of community-dwelling individuals with disabilities or chronic conditions. A gender-differentiated analysis in a cross-sectional study.

BACKGROUND: Most care for people with chronic or disabling conditions living in the community is provided in the family context, and this care is traditionally provided by women. Providing informal care has a negative impact on caregivers' quality of life, which adds to existing health inequalities associated with gender. The aim of this study was to analyze factors associated with the health-related quality of life of caregivers and to determine their differences in a gender-differentiated analysis. METHODS: An observational, cross-sectional, multicenter study was conducted in primary healthcare. A total of 218 caregivers aged 65 years or older were included, all of whom assumed the primary responsibility for caring for people with disabling conditions for at least 6 months per year and agreed to participate in the CuidaCare study. The dependent variable was health-related quality of life, assessed with the EQ-5D. The explanatory variables tested were grouped into sociodemographic variables, subjective burden, caregiving role, social support and variables related to the dependent person. The associations between these variables and health-related quality of life were estimated by fitting robust linear regression models. Separate analyses were conducted for women and men. RESULTS: A total of 72.8% of the sample were women, and 27.2% were men. The mean score on the EQ-5D for female caregivers was 0.64 (0.31); for male caregivers, it was 0.79 (0.23). There were differences by gender in the frequency of reported problems in the dimensions of pain/comfort and anxiety/depression. The variables that were associated with quality of life also differed. Having a positive depression screening was negatively associated with quality of life for both genders: -0.31 points (95% CI: -0.47; -0.15) for female caregivers and -0.48 points (95% CI: -0.92; -0.03) for male caregivers. Perceived burden was associated with quality of life in the adjusted model for women (-0.12 points; 95% CI: -0.19; -0.06), and domestic help was associated in the adjusted model for male caregivers (-0.12 points; 95% CI: -0.19; -0.05). CONCLUSIONS: Gender differences are present in informal caregiving. The impact of providing informal care is different for male and female caregivers, and so are the factors that affect their perceived quality of life. It could be useful it incorporates a gender perspective in the design of nursing support interventions for caregivers to individualize care and improve the quality of life of caregivers. TRIAL REGISTRATION: NCT01478295 [ https://ClinicalTrials.gov ]. 23/11/2011.

[Medical education and well-being: orientations towards the implementation of a positive teaching]. / Educación médica y bienestar: orientaciones para el desarrollo de una educación médica positiva.

The transition to and through college can affect the mental health of college students. The situation in medical students is particularly worrisome, considering that they have high rates of psychopathology. These mental health problems can be associated with worse academic and professional outcomes and worse patient care. In this scenario, it is relevant to look at how this problem can be addressed considering variables of both mental health and educational systems in medicine. Therefore, initiatives to promote well-being during the career are proposed. The importance of well-being at an institutional level should be defined. Also, the foundations of learning neurosciences from the point of view of well-being should be incorporated. Considering that well-being goes beyond the absence of discomfort, the role of educational environment both in learning and in mental health should be recognized. Proven effective interventions should be incorporated. It must be considered that not every initiative linked to well-being is necessarily positive and that discomfort to a certain extent can be exploited educatively as well. The well-being of medical students is a complex, dynamic and multidimensional issue. These principles are orientations for different actors of the educational process, to define how they will approach this problem in their contexts.

[Referral criteria to clinical genetics from primary care: Consensus document]. / Criterios de derivación a genética clínica desde Atención Primaria. Documento de consenso.

INTRODUCTION: Primary care (PC) is the first contact between the patient and the doctor, so it is essential to be clear about the criteria for suspecting a genetic disease and where it should be referred for study. MATERIAL AND METHODS: Four scientific societies: the Spanish Society of Family and Community Medicine (semFYC), the Spanish Association of Human Genetics (AEGH), the Spanish Association of Pediatrics (AEP) and the Spanish Society of Medical Oncology (SEOM), have reviewed the criteria for referral to the clinical genetics services of the different published guidelines with the purpose of define the recommendations for PC. CONCLUSIONS: With this consensus document, the PC doctor and pediatrician will know when, how and where to refer their patients with hereditary and/or genetic pathology to clinical genetics services.

Multimorbidity clusters among long-term breast cancer survivors in Spain: Results of the SURBCAN study.

The disease management of long-term breast cancer survivors (BCS) is hampered by the scarce knowledge of multimorbidity patterns. The aim of our study was to identify multimorbidity clusters among long-term BCS and assess their impact on mortality and health services use. We conducted a retrospective study using electronic health records of 6512 BCS from Spain surviving at least 5 years. Hierarchical cluster analysis was used to identify groups of similar patients based on their chronic diagnoses, which were assessed using the Clinical Classifications Software. As a result, multimorbidity clusters were obtained, clinically defined and named according to the comorbidities with higher observed/expected prevalence ratios. Multivariable Cox and negative binomial regression models were fitted to estimate overall mortality risk and probability of contacting health services according to the clusters identified. 83.7% of BCS presented multimorbidity, essential hypertension (34.5%) and obesity and other metabolic disorders (27.4%) being the most prevalent chronic diseases at the beginning of follow-up. Five multimorbidity clusters were identified: C1-unspecific (29.9%), C2-metabolic and neurodegenerative (28.3%), C3-anxiety and fractures (9.7%), C4-musculoskeletal and cardiovascular (9.6%) and C5-thyroid disorders (5.3%). All clusters except C5-thyroid disorders were associated with higher mortality compared to BCS without comorbidities. The risk of mortality in C4 was increased by 64% (adjusted hazard ratio 1.64, 95% confidence interval 1.52-2.07). Stratified analysis showed an increased risk of death among BCS with 5 to 10 years of survival in all clusters. These results help to identify subgroups of long-term BCS with specific needs and mortality risks and to guide BCS clinical practice regarding multimorbidity.

A higher bacterial inward BCAA transport driven by Faecalibacterium prausnitzii is associated with lower serum levels of BCAA in early adolescents.

BACKGROUND: Elevations of circulating branched-chain amino acids (BCAA) are observed in humans with obesity and metabolic comorbidities, such as insulin resistance. Although it has been described that microbial metabolism contributes to the circulating pool of these amino acids, studies are still scarce, particularly in pediatric populations. Thus, we aimed to explore whether in early adolescents, gut microbiome was associated to circulating BCAA and in this way to insulin resistance. METHODS: Shotgun sequencing was performed in DNA from fecal samples of 23 early adolescents (10-12 years old) and amino acid targeted metabolomics analysis was performed by LC-MS/MS in serum samples. By using the HUMAnN2 algorithm we explored microbiome functional profiles to identify whether bacterial metabolism contributed to serum BCAA levels and insulin resistance markers. RESULTS: We identified that abundance of genes encoding bacterial BCAA inward transporters were negatively correlated with circulating BCAA and HOMA-IR (P < 0.01). Interestingly, Faecalibacterium prausnitzii contributed to approximately ~ 70% of bacterial BCAA transporters gene count. Moreover, Faecalibacterium prausnitzii abundance was also negatively correlated with circulating BCAA (P = 0.001) and with HOMA-IR (P = 0.018), after adjusting for age, sex and body adiposity. Finally, the association between Faecalibacterium genus and BCAA levels was replicated over an extended data set (N = 124). CONCLUSIONS: We provide evidence that gut bacterial BCAA transport genes, mainly encoded by Faecalibacterium prausnitzii, are associated with lower circulating BCAA and lower insulin resistance. Based on the later, we propose that the relationship between Faecalibacterium prausnitzii and insulin resistance, could be through modulation of BCAA.