Ongoing CPR with an onboard physician.

Introduction: Recent data are not available on ongoing CPR for emergency services with an onboard physician. The aim of the present study was to identify factors associated with the decision to transport patients to hospital with ongoing CPR and examine their survival to hospital discharge with good neurological status. Methods: An observational study based on a registry of out-of-hospital cardiac arrests attended to by emergency services with an onboard physician. All OHCA cases occurring between the 1st of January and the 31st of December 2022 were included. Patients receiving ongoing CPR during transport to the hospital were compared with patients pronounced dead at the scene following arrival of the care team. The dependent variable was ongoing CPR during transport to the hospital. The main characteristics and the neurological status of patients surviving to discharge were described. Results: A total of 9321 cases were included, of which 350 (3.7%) were transported to hospital with ongoing CPR. Such patients were young (59.9 ± 20.1 years vs 64.6 ± 16.9 years; p < 0.001; 95%CI: 0.98 [0.98; 0.99]) with arrest taking place outside of the home (151 [44.5%] vs 4045 [68.01%]; p < 0.001; 95%CI: 0.41 [0.31; 0.54]) and being witnessed by EMS (126 [36.0%] vs 667 [11.0%]; p < 0.001; 95%CI: 4.31 [3.19; 5.80]), whilst initial rhythm differed from asystole (164 [47.6%] vs 4325 [73.0%]; p < 0.01; 95%CI: 0.44 [0.33; 0.60]) and a mechanical device was more often employed during resuscitation and transport to hospital (199 [56.9%] vs 2050 [33.8%]; p < 0.001; 95%CI: 2.75 [2.10; 3.59]). Seven patients (2%) were discharged alive from hospital, five with ad integrum neurological recovery (CPC1) and two with minimally impaired neurological function (CPC2). Conclusions: The strategy of ongoing CPR is uncommon in EMS with an onboard physician. Despite their limited efficacy, the availability of mechanical chest compression devices, together with the possibility of specific hospital treatments, mainly ICP and ECMO, opens up the possibility of this approach with determined patients.

Out-of-Hospital Cardiac Arrest Following the COVID-19 Pandemic.

Importance: Out-of-hospital cardiac arrest (OHCA) health care provision may be a good indicator of the recovery of the health care system involved in OHCA care following the COVID-19 pandemic. There is a lack of data regarding outcomes capable of verifying this recovery. Objective: To determine whether return to spontaneous circulation, overall survival, and survival with good neurological outcome increased in patients with OHCA since the COVID-19 pandemic was brought under control in 2022 compared with prepandemic and pandemic levels. Design, Setting, and Participants: This observational cohort study was conducted to examine health care response and survival with good neurological outcome at hospital discharge in patients treated following OHCA. A 3-month period, including the first wave of the pandemic (February 1 to April 30, 2020), was compared with 2 periods before (April 1, 2017, to March 31, 2018) and after (January 1 to December 31, 2022) the pandemic. Data analysis was performed in July 2023. Emergency medical services (EMS) serving a population of more than 28 million inhabitants across 10 Spanish regions participated. Patients with OHCA were included if participating EMS initiated resuscitation or continued resuscitation initiated by a first responder. Exposure: The pandemic was considered to be under control following the official declaration that infection with SARS-CoV-2 was to be considered another acute respiratory infection. Main Outcome and Measures: The main outcomes were return of spontaneous circulation, overall survival, and survival at hospital discharge with good neurological outcome, expressed as unimpaired or minimally impaired cerebral performance. Results: A total of 14 732 patients (mean [SD] age, 64.2 [17.2] years; 10 451 [71.2%] male) were included, with 6372 OHCAs occurring during the prepandemic period, 1409 OHCAs during the pandemic period, and 6951 OHCAs during the postpandemic period. There was a higher incidence of OHCAs with a resuscitation attempt in the postpandemic period compared with the pandemic period (rate ratio, 4.93; 95% CI, 4.66-5.22; P < .001), with lower incidence of futile resuscitation for OHCAs (2.1 per 100 000 person-years vs 1.3 per 100 000 person-years; rate ratio, 0.81; 95% CI, 0.71-0.92; P < .001). Recovery of spontaneous circulation at hospital admission increased from 20.5% in the pandemic period to 30.5% in the postpandemic period (relative risk [RR], 1.08; 95% CI, 1.06-1.10; P < .001). In the same way, overall survival at discharge increased from 7.6% to 11.2% (RR, 1.45; 95% CI, 1.21-1.75; P < .001), with 6.6% of patients being discharged with good neurological status (Cerebral Performance Category Scale categories 1-2) in the pandemic period compared with 9.6% of patients in the postpandemic period (RR, 1.07; 95% CI, 1.04-1.10; P < .001). Conclusions and Relevance: In this cohort study, survival with good neurological outcome at hospital discharge following OHCA increased significantly after the COVID-19 pandemic.

The gut microbiota is important for the maintenance of blood-cerebrospinal fluid barrier integrity.

The gut microbiota communicates with the brain through several pathways including the vagus nerve, immune system, microbial metabolites and through the endocrine system. Pathways along the humoral/immune gut microbiota-brain axis are composed of a series of vascular and epithelial barriers including the intestinal epithelial barrier, gut-vascular barrier, blood-brain barrier and blood-cerebrospinal fluid barrier. Of these barriers, the relationship between the gut microbiota and blood-cerebrospinal fluid barrier is yet to be fully defined. Here, using a germ-free mouse model, we aimed to assess the relationship between the gut microbiota and the integrity of the blood-cerebrospinal fluid barrier, which is localized to the choroid plexus epithelium. Using confocal microscopy, we visualized the tight junction protein zonula occludens-1, an integral aspect of choroid plexus integrity, as well as the choroid plexus fenestrated capillaries. Quantification of tight junction proteins via network analysis led to the observation that there was a decrease in the zonula occludens-1 network organization in germ-free mice; however, we did not observe any differences in capillary structure. Taken together, these data indicate that the blood-cerebrospinal fluid barrier is another barrier along the gut microbiota-brain axis. Future studies are required to elucidate its relative contribution in signalling from microbiota to the brain.

Microbial-derived metabolites induce actin cytoskeletal rearrangement and protect blood-brain barrier function.

The gut microbiota influences host brain function, but the underlying gut-brain axis connections and molecular processes remain unclear. One pathway along this bidirectional communication system involves circulating microbially derived metabolites, such as short-chain fatty acids (SCFAs), which include butyrate and propionate. Brain endothelium is the main interface of communication between circulating signals and the brain, and it constitutes the main component of the blood-brain barrier (BBB). Here, we used a well-established in vitro BBB model treated with physiologically relevant concentrations of butyrate and propionate with and without lipopolysaccharide (LPS) to examine the effects of SCFAs on the actin cytoskeleton and tight junction protein structure. Both SCFAs induced distinct alterations to filamentous actin directionality. SCFAs also increased tight junction protein spikes and protected from LPS-induced tight-junction mis-localization, improved BBB integrity, and modulated mitochondrial network dynamics. These findings identify the actin cytoskeletal dynamics as another target further illuminating how SCFAs can influence BBB physiology.

Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.

Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS, enabling development of CNS-targeted therapeutics. Many genetically-defined neurodegenerative disorders are dominant, favoring selective silencing of the mutant allele. In some cases, successfully targeting the mutant allele requires targeting single nucleotide polymorphism (SNP) heterozygosities. Here, we use Huntington's disease (HD) as a model. The optimized compound exhibits selective silencing of mutant huntingtin protein in patient-derived cells and throughout the HD mouse brain, demonstrating SNP-based allele-specific RNAi silencing of gene expression in vivo in the CNS. Targeting a disease-causing allele using RNAi-based therapies could be helpful in a range of dominant CNS disorders where maintaining wild-type expression is essential.

Brecha de género persistente en la parada cardiaca extrahospitalaria en España durante el periodo 2013-2018 / Persistent gender gaps in out-of-hospital cardiac arrest in Spain from 2013 through 2018

Objetivos. Examinar las diferencias de género en las características de la parada cardiaca extrahospitalaria (PCRE), los tratamientos, la supervivencia, y los cambios evolutivos en España. Método. Datos de dos series temporales (2013/2014 y 2017/2018) del registro prospectivo de PCRE (OHSCAR). Se incluyeron todos los casos consecutivos en los que intervino un equipo de emergencias. Las variables dependientes fueron las variables de atención de la PCRE, la llegada al hospital con pulso espontáneo, la supervivencia global al alta, y con buenos resultados neurológicos. El sexo fue la variable independiente. Resultados. Las mujeres fueron significativamente mayores, menos propensas a presentar una PCRE en lugar público, recibir desfibrilación externa automática, tener un ritmo inicial desfibrilable y ser atendidas por una ambulancia en menos de 15 minutos. Además, menos mujeres recibieron intervención coronaria percutánea o hipotermia al ingreso hospitalario. Tanto en 2013/2014 como en 2017/2018 las mujeres tuvieron menos probabilidades de supervivencia al ingreso hospitalario (OR = 0,52; p < 0,001; OR = 0,61; p = 0,009 respectivamente), y al alta hospitalaria (OR = 0,69; p = 0,001; OR = 0,72; p = 0,001, respectivamente) y con buenos resultados neurológicos (OR = 0,50; p < 0,001; OR = 0,63; p <0,001, respectivamente). Conclusiones. En ambos periodos las mujeres tuvieron menos probabilidades de sobrevivir y de hacerlo en buenas condiciones neurológicas. Estos resultados indican la necesidad de adoptar nuevos enfoques para abordar las diferencias de género en la PCRE. (AU)

Objective. To examine gender-related differences in the management and survival of out-of-hospital cardiac arrest (OHCA) in Spain during 2 time series. Methods. Analysis of data recorded in the prospective Spanish OHCA registry (OHSCAR in its Spanish acronym) for 2 time series (2013-2014 and 2017-2018). We included all 11036 consecutive cases in which an emergency team intervened. The dependent variables were arrival at the hospital after return of spontaneous circulation, overall survival to discharge, and overall survival with good neurological outcomes. Sex was the independent variable. We report descriptive statistics, patient group comparisons, and changes over time. Results.Women were significantly older and less likely to experience an OHCA in a public place, receive automatic external defibrillation, have a shockable heart rhythm, and be attended by an ambulance team within 15 minutes. In addition, fewer women underwent percutaneous coronary interventions or received treatment for hypothermia on admission to the hospital. In 2013-2014 and 2017-2018, respectively, the likelihood of survival was lower for women than men on admission (odds ratio [OR], 0.52 vs OR, 0.61; P < .001 and P = .009 in the 2 time series) and at discharge (OR, 0.69 vs 0.72 for men; P = .001 in both time series). Survival with good neurological outcomes was also less likely in women (OR, 0.50 vs 0.63; P < .001 in both series). Conclusions. The odds for survival and survival with good neurological outcomes were lower for women in nearly all patient groups in both time series. These findings suggest the need to adopt new approaches to address gender differences in OHCA. (AU)

PK-modifying anchors significantly alter clearance kinetics, tissue distribution, and efficacy of therapeutics siRNAs.

Effective systemic delivery of small interfering RNAs (siRNAs) to tissues other than liver remains a challenge. siRNAs are small (∼15 kDa) and therefore rapidly cleared by the kidneys, resulting in limited blood residence times and tissue exposure. Current strategies to improve the unfavorable pharmacokinetic (PK) properties of siRNAs rely on enhancing binding to serum proteins through extensive phosphorothioate modifications or by conjugation of targeting ligands. Here, we describe an alternative strategy for enhancing blood and tissue PK based on dynamic modulation of the overall size of the siRNA. We engineered a high-affinity universal oligonucleotide anchor conjugated to a high-molecular-weight moiety, which binds to the 3' end of the guide strand of an asymmetric siRNA. Data showed a strong correlation between the size of the PK-modifying anchor and clearance kinetics. Large 40-kDa PK-modifying anchors reduced renal clearance by ∼23-fold and improved tissue exposure area under the curve (AUC) by ∼26-fold, resulting in increased extrahepatic tissue retention (∼3- to 5-fold). Furthermore, PK-modifying oligonucleotide anchors allowed for straightforward and versatile modulation of blood residence times and biodistribution of a panel of chemically distinct ligands. The effects were more pronounced for conjugates with low lipophilicity (e.g., N-Acetylgalactosamine [GalNAc]), where significant improvement in uptake by hepatocytes and dose-dependent silencing in the liver was observed.

Persistent gender gaps in out-of-hospital cardiac arrest in Spain from 2013 through 2018. / Brecha de género persistente en la parada cardiaca extrahospitalaria en España durante el periodo 2013-2018.

OBJECTIVES: To examine gender-related differences in the management and survival of out-of-hospital cardiac arrest (OHCA) in Spain during 2 time series. MATERIAL AND METHODS: Analysis of data recorded in the prospective Spanish OHCA registry (OHSCAR in its Spanish acronym) for 2 time series (2013-2014 and 2017-2018). We included all 11 036 consecutive cases in which an emergency team intervened. The dependent variables were arrival at the hospital after return of spontaneous circulation, overall survival to discharge, and overall survival with good neurological outcomes. Sex was the independent variable. We report descriptive statistics, patient group comparisons, and changes over time. RESULTS: Women were significantly older and less likely to experience an OHCA in a public place, receive automatic external defibrillation, have a shockable heart rhythm, and be attended by an ambulance team within 15 minutes. In addition, fewer women underwent percutaneous coronary interventions or received treatment for hypothermia on admission to the hospital. In 2013-2014 and 2017-2018, respectively, the likelihood of survival was lower for women than men on admission (odds ratio [OR], 0.52 vs OR, 0.61; P .001 and P = .009 in the 2 time series) and at discharge (OR, 0.69 vs 0.72 for men; P = .001 in both time series). Survival with good neurological outcomes was also less likely in women (OR, 0.50 vs 0.63; P .001 in both series). CONCLUSION: The odds for survival and survival with good neurological outcomes were lower for women in nearly all patient groups in both time series. These findings suggest the need to adopt new approaches to address gender differences in OHCA.

OBJETIVO: Examinar las diferencias de género en las características de la parada cardiaca extrahospitalaria (PCRE), los tratamientos, la supervivencia, y los cambios evolutivos en España. METODO: Datos de dos series temporales (2013/2014 y 2017/2018) del registro prospectivo de PCRE (OHSCAR). Se incluyeron todos los casos consecutivos en los que intervino un equipo de emergencias. Las variables dependientes fueron las variables de atención de la PCRE, la llegada al hospital con pulso espontáneo, la supervivencia global al alta, y con buenos resultados neurológicos. El sexo fue la variable independiente. RESULTADOS: Las mujeres fueron significativamente mayores, menos propensas a presentar una PCRE en lugar público, recibir desfibrilación externa automática, tener un ritmo inicial desfibrilable y ser atendidas por una ambulancia en menos de 15 minutos. Además, menos mujeres recibieron intervención coronaria percutánea o hipotermia al ingreso hospitalario. Tanto en 2013/2014 como en 2017/2018 las mujeres tuvieron menos probabilidades de supervivencia al ingreso hospitalario (OR = 0,52; p 0,001; OR = 0,61; p = 0,009 respectivamente), y al alta hospitalaria (OR = 0,69; p = 0,001; OR = 0,72; p = 0,001, respectivamente) y con buenos resultados neurológicos (OR = 0,50; p 0,001; OR = 0,63; p 0,001, respectivamente). CONCLUSIONES: En ambos periodos las mujeres tuvieron menos probabilidades de sobrevivir y de hacerlo en buenas condiciones neurológicas. Estos resultados indican la necesidad de adoptar nuevos enfoques para abordar las diferencias de género en la PCRE.

Typology of content warnings and trigger warnings: Systematic review.

Content and trigger warnings give information about the content of material prior to receiving it. Different typologies of content warnings have emerged across multiple sectors, including health, social media, education and entertainment. Benefits arising from their use are contested, with recent empirical evidence from educational sectors suggesting they may raise anxiety and reinforce the centrality of trauma experience to identity, whilst benefits relate to increased individual agency in making informed decisions about engaging with content. Research is hampered by the absence of a shared inter-sectoral typology of warnings. The aims of this systematic review are to develop a typology of content warnings and to identify the contexts in which content warnings are used. The review was pre-registered (ID: CRD42020197687, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020197687) and used five sources: electronic databases covering multiple sectors (n = 19); table of contents from multi-sectoral journals (n = 5), traditional and social media websites (n = 53 spanning 36 countries); forward and backward citation tracking; and expert consultation (n = 15). In total, 6,254 documents were reviewed for eligibility and 136 documents from 32 countries were included. These were synthesised to develop the Narrative Experiences Online (NEON) content warning typology, which comprises 14 domains: Violence, Sex, Stigma, Disturbing content, Language, Risky behaviours, Mental health, Death, Parental guidance, Crime, Abuse, Socio-political, Flashing lights and Objects. Ten sectors were identified: Education, Audio-visual industries, Games and Apps, Media studies, Social sciences, Comic books, Social media, Music, Mental health, and Science and Technology. Presentation formats (n = 15) comprised: education materials, film, games, websites, television, books, social media, verbally, print media, apps, radio, music, research, DVD/video and policy document. The NEON content warning typology provides a framework for consistent warning use and specification of key contextual information (sector, presentation format, target audience) in future content warning research, allowing personalisation of content warnings and investigation of global sociopolitical trends over time.

The blood-brain barrier in aging and neurodegeneration.

The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-related disorders. Several drugs have been explored, thus far, to protect or restore BBB function. With the recent connection between the BBB and gut microbiota, microbial-derived metabolites have been explored for their capabilities to protect and restore BBB physiology. This review, will focus on the vital components that make up the BBB, dissect levels of disruption of the barrier, and discuss current drugs and therapeutics that maintain barrier integrity and the recent discoveries of effects microbial-derived metabolites have on BBB physiology.

Gender and Social Inequalities in Awareness of Coronary Artery Disease in European Countries.

Coronary artery disease (CAD) is the single leading cause of death in Europe and the most common form of cardiovascular disease. Little is known about awareness in the European population. A cross-sectional telephone survey of 2609 individuals from six European countries was conducted to gather information on perceptions of CAD, risk factors, preventive measures, knowledge of heart attack symptoms and ability to seek emergency medical care. Level of awareness was compared according to gender, age, socioeconomic status (SES) and educational level. Women were approximately five times less likely than men to consider heart disease as a main health issue or leading cause of death (OR = 0.224, 95% CI: 0.178-0.280, OR = 0.196, 95% CI: 0.171-0.226). Additionally, women were significantly less likely to have ever had a cardiovascular screening test (OR = 0.515, 95% CI: 0.459-0.578). Only 16.3% of men and 15.3% of women were able to spontaneously identify the main symptoms of a heart attack. Almost half of the sample failed to state that they would call emergency services in case of a cardiac event. Significant differences according to age, SES and education were found for many indicators amongst both men and women. Development of a European strategy targeting improved awareness of CAD and reduced gender and social inequalities within the European population is warranted.

Short chain fatty acids: Microbial metabolites for gut-brain axis signalling.

The role of the intestinal microbiota as a regulator of gut-brain axis signalling has risen to prominence in recent years. Understanding the relationship between the gut microbiota, the metabolites it produces, and the brain will be critical for the subsequent development of new therapeutic approaches, including the identification of novel psychobiotics. A key focus in this regard have been the short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fibre, which include butyrate, acetate, and propionate. Ongoing research is focused on the entry of SCFAs into systemic circulation from the gut lumen, their migration to cerebral circulation and across the blood brain barrier, and their potential to exert acute and chronic effects on brain structure and function. This review aims to discuss our current mechanistic understanding of the direct and indirect influence that SCFAs have on brain function, behaviour and physiology, which will inform future microbiota-targeted interventions for brain disorders.

Psychometric Properties of the Work Ability Index in Health Centre Workers in Spain.

The aim of the present study is to analyse the psychometric properties of the work ability index (WAI) within a sample of Spanish health centre workers. The WAI was translated into Spanish using transcultural and forward-backward translation processes and administered to 1184 Spanish health centre workers. Internal consistency, predictive validity, and discriminative ability were examined. Exploratory factor analysis, via principal components analysis and confirmatory factor analysis, determined the most appropriate questionnaire structure. All indices in relation to predictive validity and reliability were acceptable. Exploratory factor analysis supported validity of the one-factor structure, however, confirmatory factor analysis suggested better properties in relation to a two-factor structure (χ2 = 59.52; CFI = 0.98; TLI = 0.96; RMSEA = 0.06). Items 3, 4, and 5 loaded onto factor one, and items 1, 2, 6, and 7 loaded onto factor two. The two factors could be broadly described as "subjectively estimated work ability" and "ill-health-related ability". The WAI is valid and reliable when administered to health centre workers in Spain. In contrast to that suggested by studies conducted in other countries, future research and practical application with similar respondents and settings should proceed using the two-factor structure.

Comparative route of administration studies using therapeutic siRNAs show widespread gene modulation in Dorset sheep.

siRNAs comprise a class of drugs that can be programmed to silence any target gene. Chemical engineering efforts resulted in development of divalent siRNAs (di-siRNAs), which support robust and long-term efficacy in rodent and nonhuman primate brains upon direct cerebrospinal fluid (CSF) administration. Oligonucleotide distribution in the CNS is nonuniform, limiting clinical applications. The contribution of CSF infusion placement and dosing regimen on relative accumulation, specifically in the context of large animals, is not well characterized. To our knowledge, we report the first systemic, comparative study investigating the effects of 3 routes of administration - intrastriatal (i.s.), i.c.v., and intrathecal catheter to the cisterna magna (ITC) - and 2 dosing regimens - single and repetitive via an implanted reservoir device - on di-siRNA distribution and accumulation in the CNS of Dorset sheep. CSF injections (i.c.v. and ITC) resulted in similar distribution and accumulation across brain regions. Repeated dosing increased homogeneity, with greater relative deep brain accumulation. Conversely, i.s. administration supported region-specific delivery. These results suggest that dosing regimen, not CSF infusion placement, may equalize siRNA accumulation and efficacy throughout the brain. These findings inform the planning and execution of preclinical and clinical studies using siRNA therapeutics in the CNS.

Profiles for identifying problematic dietary habits in a sample of recreational Spanish cyclists and triathletes.

There is a lack of sufficient information on the dietary intake and nutritional supplementation of recreational endurance athletes throughout the year. The present observational study sought to assess the dietary intake and nutritional supplementation habits of recreational cyclists and triathletes from Spain. 4,037 cyclists and triathletes completed self-report measures. Nutritional profiles were developed and differences were examined according to sporting discipline and gender. Differences between groups were compared using the Mann-Whitney U or chi-squared test. Next, micro- and macro-nutrients were grouped according to whether or not guideline intake amounts were met. The clustering of dietary habits was then examined via K-means cluster analysis. Triathletes took more supplements than cyclists (X2 = 36.489; p value = .000) and females took more supplements than males (X2 = 5.920; p value = .017). Females and triathletes reported greater protein and CHO consumption than males and cyclists, respectively. Triathletes also reported a higher consumption of total fat, MUFA, PUFA, EPA, DHA and fibre. Females and triathletes tended to consume more vitamins and minerals than males and cyclists, respectively. Two main dietary habit clusters emerged which may be used to inform nutritional interventions targeting recreational athletes not meeting nutritional requirements. There is an imbalance in the main nutrients making up the diet of recreational Spanish athletes, characterised by insufficient CHO and excessive protein.

Mediational Occupational Risk Factors Pertaining to Work Ability According to Age, Gender and Professional Job Type.

The predictive value of work ability for several health and occupational outcomes is well known. Maintaining the ability to work of all employees has become an important topic in research although some evidence suggests that some groups of workers need greater attention than others. Healthcare workers (x¯ = 54.46 ± 5.64 years) attending routine occupational health checkups completed their work ability, occupational risk and sociodemographic measures. An analysis examined whether work ability differed according to gender, age and professional category. Mediation of these relationships by occupational risk variables, such as work-family conflict, was examined. Females and older adults had worse work ability than their counterparts. Professional group was not independently associated. Gender-related differences were mediated by current and historic ergonomic risk, psychosocial risk and work-family conflict. Age-related differences were mediated by violence/discrimination at work. All job risk variables, apart from current ergonomic risk, mediated associations between professional category and work ability. The present study identified the importance of risk variables for the work ability of health workers according to gender, age and professional job type. Perceptions of work-family conflict and violence-discrimination seem particularly important and should be considered when targeting improvements in work ability.

Likelihood of suffering from an eating disorder in a sample of Spanish cyclists and triathletes.

BACKGROUND: During recent years, there has been increasing interest in the study of eating disorders within sports practitioners, with prevalence being reported to be higher than in the general population. The aim of this study was to describe and predict eating disorders according to sex, body mass index, age and sport discipline within a sample of athletes. METHODS: A sample of 4037 cyclists and triathletes from across Spain was selected. Athletes self-reported demographic characteristics and completed the revised restraint scale, SCOFF questionnaire and Mediterranean diet adherence screener. To be eligible for inclusion, participants had to be over eighteen years old. RESULTS: Males were significantly less likely than females (p < 0.001; OR = 0.33), and triathletes (p < 0.01; OR = 0.76) were less likely than cyclists to suffer from an eating disorder. Possibility of suffering from an eating disorder increased with increasing body mass index (p < 0.001; OR = 1.38) and decreasing age (p < 0.001; OR = 0.97). CONCLUSION: Findings suggest that the roles of sex, sport discipline, age and body mass index predict risk factors for eating disorders in a sample of Spanish athletes. Clinical diagnosis seems necessary to better understand the factors and mechanisms at play when Spanish athletes develop an eating disorder. TRIAL REGISTRATION: Ethics Committee of the University of Granada (N°883) data: 16/11/2015.

Influence of the Covid-19 pandemic on out-of-hospital cardiac arrest. A Spanish nationwide prospective cohort study.

AIMS: The influence of the COVID-19 pandemic on attendance to out-of-hospital cardiac arrest (OHCA) has only been described in city or regional settings. The impact of COVID-19 across an entire country with a high infection rate is yet to be explored. METHODS: The study uses data from 8629 cases recorded in two time-series (2017/2018 and 2020) of the Spanish national registry. Data from a non-COVID-19 period and the COVID-19 period (February 1st-April 30th 2020) were compared. During the COVID-19 period, data a further analysis comparing non-pandemic and pandemic weeks (defined according to the WHO declaration on March 11th, 2020) was conducted. The chi-squared analysis examined differences in OHCA attendance and other patient and resuscitation characteristics. Multivariate logistic regression examined survival likelihood to hospital admission and discharge. The multilevel analysis examined the differential effects of regional COVID-19 incidence on these same outcomes. RESULTS: During the COVID-19 period, the incidence of resuscitation attempts declined and survival to hospital admission (OR = 1.72; 95%CI = 1.46-2.04; p < 0.001) and discharge (OR = 1.38; 95%CI = 1.07-1.78; p = 0.013) fell compared to the non-COVID period. This pattern was also observed when comparing non-pandemic weeks and pandemic weeks. COVID-19 incidence impinged significantly upon outcomes regardless of regional variation, with low, medium, and high incidence regions equally affected. CONCLUSIONS: The pandemic, irrespective of its incidence, seems to have particularly impeded the pre-hospital phase of OHCA care. Present findings call for the need to adapt out-of-hospital care for periods of serious infection risk. STUDY REGISTRATION NUMBER: ISRCTN10437835.

2'-O-Methyl at 20-mer Guide Strand 3' Termini May Negatively Affect Target Silencing Activity of Fully Chemically Modified siRNA.

Small interfering RNAs (siRNAs) have the potential to treat a broad range of diseases. siRNAs need to be extensively chemically modified to improve their bioavailability, safety, and stability in vivo. However, chemical modifications variably impact target silencing for different siRNA sequences, making the activity of chemically modified siRNA difficult to predict. Here, we systematically evaluated the impact of 3' terminal modifications (2'-O-methyl versus 2'-fluoro) on guide strands of different length and showed that 3' terminal 2'-O-methyl modification negatively impacts activity for >60% of siRNA sequences tested but only in the context of 20- and not 19- or 21-nt-long guide strands. These results indicate that sequence, modification pattern, and structure may cooperatively affect target silencing. Interestingly, the introduction of an extra 2'-fluoro modification in the seed region at guide strand position 5, but not 7, may partially compensate for the negative impact of 3' terminal 2'-O-methyl modification. Molecular modeling analysis suggests that 2'-O-methyl modification may impair guide strand interactions within the PAZ domain of argonaute-2, which may affect target recognition and cleavage, specifically when guide strands are 20-nt long. Our findings emphasize the complex nature of modified RNA-protein interactions and contribute to design principles for chemically modified siRNAs.