Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.

Antarctic marine sediment as a source of filamentous fungi-derived antimicrobial and antitumor compounds of pharmaceutical interest.

Antarctica harbors a microbial diversity still poorly explored and of inestimable biotechnological value. Cold-adapted microorganisms can produce a diverse range of metabolites stable at low temperatures, making these compounds industrially interesting for biotechnological use. The present work investigated the biotechnological potential for antimicrobial and antitumor activity of filamentous fungi and bacteria isolated from marine sediment samples collected at Deception Island, Antarctica. A total of 89 microbial isolates were recovered from marine sediments and submitted to an initial screening for L-glutaminase with antitumoral activity and for antimicrobial metabolites. The isolates Pseudogymnoascus sp. FDG01, Pseudogymnoascus sp. FDG02, and Penicillium sp. FAD33 showed potential antiproliferative action against human pancreatic carcinoma cells while showing no toxic effect on non-tumor cells. The microbial extracts from unidentified three bacteria and four filamentous fungi showed antibacterial activity against at least one tested pathogenic bacterial strain. The isolate FDG01 inhibited four bacterial species, while the isolate FDG01 was active against Micrococcus luteus in the minimal inhibitory concentration of 0.015625 µg mL -1. The results pave the way for further optimization of enzyme production and characterization of enzymes and metabolites found and reaffirm Antarctic marine environments as a wealthy source of compounds potentially applicable in the healthcare and pharmaceutical industry.

Changes in the expression of genes encoding xanthophyl acyltransferases during the postharvest ripening of avocado (Persea americana) fruit.

BACKGROUND: Avocado fruit is rich in xanthophylls, which have been related to positive effects on human health. Xanthophyl acetyltransferases (XATs) are enzymes catalyzing the esterification of carboxylic acids to the hydroxyl group of the xanthophyll molecule. This esterification is thought to increase the lipophilic nature of the xanthophyll and its stability in a lipophilic environment. Studies on XATs in fruits are very scarce, and no studies had been carried out in avocado fruit during postharvest. The objective of this work was to investigate the changes in the expression of genes encoding XAT, during avocado fruit ripening. RESULTS: Avocado fruits were obtained from a local market and stored at 15 °C for 8 days. The fruit respiration rate, ethylene production, and fruit peel's color space parameters (L*, a*, b*) were measured during storage. Fruit mesocarp samples were taken after 1, 3, 5, and 7 days of storage and frozen with liquid nitrogen. Total RNA was extracted from fruit mesocarp, and the quantification of the two genes designated as COGE_ID: 936743791 and COGE_ID: 936800185 encoding XATs was performed with real-time quantitative reverse transcription polymerase chain reaction using actin as a reference gene. The presence of a climacteric peak and large changes in color were recorded during postharvest. The two genes studied showed a large expression after 3 days of fruit storage. CONCLUSIONS: We conclude that during the last stages of ripening in avocado fruit there was an active esterification of xanthophylls with carboxylic acids, which suggests the presence of esterified xanthophylls in the fruit mesocarp. © 2024 Society of Chemical Industry.

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.

Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: A systematic review.

BACKGROUND: Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically. METHODS: We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk. RESULTS: Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies. LIMITATIONS: Substantial heterogeneity among the studies precluded performing a meta-analysis. CONCLUSION: Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention.

Association of Frailty and Cardiopulmonary Resuscitation Outcomes in Older U.S. Veterans.

Objectives: Determine the association between frailty and immediate survival of cardiopulmonary resuscitation (CPR) in older Veterans. Secondary outcomes: compare in-hospital mortality, duration of resuscitation efforts, hospital and intensive care unit (ICU) length of stay, neurologic outcomes, and discharge disposition between frail and non-frail Veterans. Methods: Retrospective cohort study including Veterans 50 years and older, who were "Full Code" and had in-hospital cardiac arrest between 7/1/2017 and 6/30/2020, at the Miami VAMC. Frailty Index for the VA (VA-FI) was used to determine frailty status. Immediate Survival was determined by return of spontaneous circulation (ROSC) and in-hospital mortality was determined by all-cause mortality. We compared outcomes between frail and non-frail Veterans using chi-square test. After adjusting for age, gender, race, and previous hospitalizations, we used multivariate binomial logistic regression with 95% confidence intervals to analyze the relationship between immediate survival and frailty, and in-hospital mortality and frailty. Results: 91% Veterans were non-Hispanic, 49% Caucasian, 96% male, mean age 70.7 ± 8.5 years, 73% frail and 27% non-frail. Seventy-six (65.5%) Veterans had ROSC, without difference by frailty status (P = .891). There was no difference based on frailty status of in-hospital mortality, discharge disposition, or neurologic outcomes. Frail and non-frail Veterans had resuscitation efforts lasting the same amount of time. Conclusions and Implications: CPR outcomes were not different depending on frailty status in our Veteran population. With these results, we cannot use frailty - as measured by the VA-FI - as a prognosticator of CPR outcomes in Veterans.

Geographical approach analysis of the impact of air pollution on newborn intrauterine growth and cord blood DNA damage in Mexico City.

BACKGROUND: Few epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA). METHODS: This cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households. RESULTS: Contaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term. IMPACT: Results suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.

Factores de predicción relevantes en la supervivencia de pacientes con síndrome antifosfolípido / Relevants predictions factors in the survival of patients with antiphospholipid syndrome

Introducción: Los pacientes con síndrome antifosfolípido desarrollan morbilidad y mortalidad significativas a pesar del tratamiento actual. Es imperativo, identificar factores pronósticos y medidas terapéuticas para prevenir estas complicaciones. Objetivo: Determinar los factores relevantes en la predicción de la supervivencia en los pacientes con síndrome antifosfolípido. Métodos: Se realizó un estudio longitudinal analítico de una cohorte histórica de personas con síndrome antifosfolípido, diagnosticados, según los criterios de Sapporo/Sydney y colaboradores en la consulta de enfermedades autoinmunes sistémicas del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», Villa Clara, del año 2000 al 2015. Se estudiaron variables demográficas y clínicas. En cada caso se determinó el tiempo de supervivencia con relación al evento muerte. Se aplicó el método de Kaplan Meier para calcular la supervivencia global y determinar las variables predictoras de la mortalidad. Según el estudio de los estadígrafos de comparación interestratos(Log-Rank) se demostró la significación estadística con la prueba de Chi cuadrado de homogeneidad. Resultados: De los 128 pacientes estudiados, 118 fueron femeninos y 10 masculinos (111 de piel blanca y 17 no blancos). La supervivencia global fue de 67,1 % con una media de 13,37 años. Las variables más relevantes que aportaron a la mortalidad en relación con menor supervivencia fueron: leucopenia, linfopenia, color de la piel no blanca, y el no uso de aspirina, con medias de supervivencia de 8,83; 8,17; 10,72; 12,10 años, respectivamente. Conclusiones: La identificación temprana de los factores pronósticos de supervivencia permite implementar estrategias oportunas e individualizadas en pacientes con síndrome antifosfolípido.

Introduction: patients with antiphospholipid syndrome develop significant morbidity and mortality despite current treatment. Identifying prognostic factors and therapeutic measures to prevent these complications is indispensable. Objective: to determine relevant factors in the prediction of survival in patients with antiphospholipid syndrome. Methods: a longitudinal analytical study was carried out on cohorts with antiphospholipid syndrome who were diagnosed according to the Sapporo-Sydney criteria and collaborators in the systemic autoimmune disease consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Villa Clara from 2000 to 2015. Demographic and clinical variables were studied. The survival time in relation to the death event was determined in each case. The Kaplan - Meier method was applied to calculate overall survival and determine the predictor variables for mortality. According to the study of inter-strata comparison statistics (Log-Rank), statistical significance was demonstrated with the Chi-square test of homogeneity. Results: a number of 118 patients were female and 10 male from the 128 studied (111 white-skinned and 17 non-white). Overall survival was 67.1% with a mean of 13.37 years. The most relevant variables that contributed to mortality in relation to lower survival were leukopenia, lymphopenia, non-white skin color and non-use of aspirin, with mean survival of 8.83; 8.17; 10.72; 12.10 years, respectively. Conclusions: the early identification of survival prognostic factors allows us the implementation of timely and individualized strategies in patients with antiphospholipid syndrome.

Lower Limb Degloving Trauma Reconstruction: A Case Report.

Degloving injuries are caused by trauma with shear mechanisms, usually secondary to being run over in traffic accidents. It is characterized by the avulsion of skin and subcutaneous tissue, generating coverage deficit, and in severe cases, loss of the affected limb. Herein, we discuss a case of a six-year-old male run over by a truck, receiving a direct impact on the left lower extremity with a rubber tire. Debridement and surgical cleaning were performed and a negative pressure system was placed. Subsequently, dermal matrix and partial-thickness skin grafts were placed as coverage after the creation of a viable grafting bed.

Association between the Neutrophil-to-Lymphocyte Ratio and Inpatient Mortality in Hospitalized Older Veterans with COVID-19 Infection.

OBJECTIVES: Determine the association of high neutrophil-to-lymphocyte ratio (NLR) values with inpatient mortality and other outcomes in older veterans hospitalized with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective, multicenter, cohort study of hospitalized adults, with laboratory-confirmed COVID-19 infection who were studied for 1 year after discharge or until death. The NLR was categorized into tertiles, and we determined frailty status with the 31-item Veterans Affairs Frailty Index. Multivariate logistic regression and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were performed to assess the association between NLR and clinical outcomes. RESULTS: The study included 615 hospitalized adult veterans, mean age 66.12 (standard deviation 14.79) years, 93.82% (n = 577) male, 57.56% (n = 354) White, 81.0% (n = 498) non-Hispanic, median body mass index of 30.70 (interquartile range 25.64-34.99, standard deviation 7.13), and median length of stay of 8 days (interquartile range 3-15). Individuals in the middle and upper tertile groups had higher inpatient mortality (8.37%, n = 17 and 18.36%, n = 38, respectively) as compared with the lower tertile (2.93%, n = 6, P < 0.001). Compared with the lowest tertile, the middle and upper tertiles had a higher risk of inpatient mortality (aOR 3.75, 95% CI 1.38-10.21, P = 0.01, and aOR 8.13, 95% CI 3.18-20.84, P < 0.001, respectively). The highest tertile had a higher odds of intensive care unit admission (aOR 4.47, 95% CI 2.33-8.58, P < 0.001) and intensive care unit transfer (aOR 3.54, 95% CI 1.84-6.81, P < 0.001). CONCLUSIONS: The NLR score is a clinically useful tool to predict in-hospital mortality in older patients with COVID-19.

Impact of Sustained Fructose Consumption on Gastrointestinal Function and Health in Wistar Rats: Glycoxidative Stress, Impaired Protein Digestion, and Shifted Fecal Microbiota.

The gastrointestinal tract (GIT) is the target of assorted pathological conditions, and dietary components are known to affect its functionality and health. In previous in vitro studies, we observed that reducing sugars induced protein glycoxidation and impaired protein digestibility. To gain further insights into the pathophysiological effects of dietary sugars, Wistar rats were provided with a 30% (w/v) fructose water solution for 10 weeks. Upon slaughter, in vivo protein digestibility was assessed, and the entire GIT (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Additionally, the impact of sustained fructose intake on colonic microbiota was also evaluated. High fructose intake for 10 weeks decreased protein digestibility and promoted changes in the physiological digestion of proteins, enhancing intestinal digestion rather than stomach digestion. Moreover, at colonic stages, the oxidative stress was harmfully increased, and both the microbiota and the intraluminal colonic metabolome were modified.

Age-Dependent Sex Differences in the Prevalence of Selective Serotonin Reuptake Inhibitor Treatment: A Retrospective Cohort Analysis.

Background: Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. Materials and Methods: We conducted a retrospective analysis of the RIGHT study. Using electronic prescriptions, we assessed 12-month prevalence of antidepressant treatment. Sex differences and age-sex interactions were evaluated using multivariable logistic regression and flexible recursive smoothing splines. Results: The sample consisted of 11,087 participants (60% women). Antidepressant prescription prevalence was 22.24% (27.96% women, 13.58% men). After adjusting for age and enrollment year, women had significantly greater odds of antidepressant prescription (odds ratio = 2.29; 95% confidence interval = 2.07, 2.54). Furthermore, selective serotonin reuptake inhibitors (SSRIs) had a significant age-sex interaction. While SSRI prescriptions in men showed a sustained decrease with age, there was no such decline for women until after reaching ∼50 years of age. There are important limitations to consider in this study. Electronic prescription data were cross-sectional; information on treatment duration or adherence was not collected; this cohort is not nationally representative; and enrollment occurred over a broad period, introducing confounding by changes in temporal prescribing practices. Conclusions: Underscored by the significant interaction between age and sex on odds of SSRI prescription, our results warrant age to be incorporated as a mediator when investigating sex differences in mental illness, especially mood disorders and their treatment.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. RESULTS: Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. CONCLUSION: Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

Mononeuritis Multiplex Due to Hansen's Disease: A Look Through Ultrasound and Electrodiagnosis.

Hansen's disease is caused by Mycobacterium leprae. This bacillus can invade the peripheral nerves asymmetrically, including the ulnar, median, and radial nerves, causing mononeuritis multiplex. We present the case of a 41-year-old man with a history of Hansen's disease with sensory and motor symptoms. Electrodiagnostic studies and ultrasound showed asymmetric lesions of the median, ulnar, and radial nerves. Because this is the main complication of this pathology, electrodiagnosis is clearly valuable for its diagnosis, demonstrating axonal and myelin involvement, as well as signs of denervation and reinnervation. Ultrasound is valuable in the detection, diagnosis, and assessment of the extent of mononeuritis multiplex due to Hansen's disease. It aids in identifying significant inflammatory deterioration, as indicated by increased blood flow in the nerves and enlargement of the nerves. This technique allows for the exploration of nerves such as the ulnar nerve and branches of the brachial plexus. In a complementary way, ultrasound provides information on the severity of the disease. Early diagnosis of this entity is essential because it can generate aesthetic and functional permanent affectation.

Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves.

BACKGROUND: Older populations have suffered the highest rates of SARS-CoV-2 infection and associated complications, including Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Frailty is a geriatric syndrome that often coexists with COVID-19 infection. The vulnerability to stressors caused by multisystemic dysfunction that characterizes frailty may predispose older adults to develop PASC. METHODS: Retrospective cohort study using the VA COVID-19 Shared Data Resource to identify US veterans testing positive for SARS-CoV-2 between July 2021 and February 2022, without prior positive tests and who were alive 30 days after infection. Frailty was calculated using a 31-item VA Frailty Index generated from electronic health records. We categorized Veterans into robust (FI ≤ 0.10), prefrail (FI: >0.10- < 0.21), and frail (FI ≥ 0.21). We assessed the association between frailty and PASC and vaccination and PASC using Cox survival model, adjusting for covariates. RESULTS: We identified 245,857 COVID-19-positive veterans surviving 30 days after infection. The mean age was 57.5 ± 16.5 years; 87.2% were males, 68.1% were white, and 9.0% were Hispanic. Almost half of the sample (48.9%) were classified as robust, while 28.3% were pre-frail and 22.7% were frail; 99,886 (40.6%) were fully vaccinated, and 33,516 (13.6%) received booster doses. Over a median follow-up of 143 days (IQR = 101), 23,890 (9.7%) patients developed PASC. Within 6 months after infection, frailty and pre-frailty were associated with a 41% (adjusted HR [aHR]:1.40 (95% CI: 1.35-1.47) and 15% (aHR: 1.17 (95% CI: 1.11-1.19) increase in the risk of PASC compared with the robust, respectively. Vaccination and booster doses before infection were associated with a 27% (aHR: 0.73 (95% CI: 0.71-0.75) and 33% (aHR: 0.66 (95% CI: 0.63-0.69) reduction in the risk of developing PASC, respectively. CONCLUSIONS: Frailty was associated with an increased risk of developing PASC. Vaccination was associated with a decreased risk of PASC, further reduced by booster doses. Early recognition of frailty in patients with COVID-19 may assist in the early identification and management of PASC.

GPS tracking analyses reveal finely-tuned shorebird space use and movement patterns throughout the non-breeding season in high-latitude austral intertidal areas.

BACKGROUND: Long-distance migratory birds spend most of their annual cycle in non-breeding areas. During this period birds must meet their daily nutritional needs and acquire additional energy intake to deal with future events of the annual cycle. Therefore, patterns of space use and movement may emerge as an efficient strategy to maintain a trade-off between acquisition and conservation of energy during the non-breeding season. However, there is still a paucity of research addressing this issue, especially in trans-hemispheric migratory birds. METHODS: Using GPS-tracking data and a recently developed continuous-time stochastic process modeling framework, we analyzed fine-scale movements in a non-breeding population of Hudsonian godwits (Limosa haemastica), a gregarious long-distance migratory shorebird. Specifically, we evaluated if these extreme migrants exhibit restricted, shared, and periodic patterns of space use on one of their main non-breeding grounds in southern South America. Finally, via a generalized additive model, we tested if the observed patterns were consistent within a circadian cycle. RESULTS: Overall, godwits showed finely-tuned range-residence and periodic movements (each 24-72 h), being similar between day and night. Remarkably, range-resident individuals segregated spatially into three groups. In contrast, a smaller fraction of godwits displayed unpredictable and irregular movements, adding functional connectivity within the population. CONCLUSIONS: In coastal non-breeding areas where resource availability is highly predictable due to tidal cycles, range-resident strategies during both the day and night are the common pattern in a long-distance shorebird population. Alternative patterns exhibited by a fraction of non-resident godwits provide functional connectivity and suggest that the exploratory tendency may be essential for information acquisition and associated with individual traits. The methodological approach we have used contributes to elucidate how the composition of movement phases operates during the non-breeding season in migratory species and can be replicated in non-migratory species as well. Finally, our results highlight the importance of considering movement as a continuum within the annual cycle.

Pore-forming activity of S. pneumoniae pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin.

Streptococcus pneumoniae, a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration in vitro and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by S. pneumoniae at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of S. pneumoniae remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type S. pneumoniae restored translocation by a PLY-deficient mutant, indicating that PLY can act in trans. Investigating the contribution of S. pneumoniae infection on apical junction complexes in the absence of PMN transmigration, we found that S. pneumoniae infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that S. pneumoniae encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus, S. pneumoniae triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.

Implantación de un equipo de asistencia al trauma grave. Análisis de la activación y tiempos de asistencia en pacientes ingresados en UCI / Implementation of a severe trauma assistance team: Analysis of activation and attendance times in patients admitted to the ICU

Objetivo Analizar los factores asociados a la activación del equipo de asistencia al trauma grave (EATG) en pacientes que ingresan en la Unidad de Cuidados Intensivos (UCI), medir su repercusión en los tiempos de asistencia, y analizar los grupos de pacientes según activación y nivel de afectación anatómica. Diseño Estudio de cohortes prospectivo del trauma grave que ingresan en UCI. Desde junio 2017 a mayo 2019. Factores de riesgo de la activación analizados con regresión logística y árbol de clasificación tipo CART. Ámbito UCI hospital de segundo nivel. Pacientes Pacientes ingresados de forma consecutiva. Intervenciones Ninguna. Variables de intereses principales Activación del EATG. Variables demográficas. Puntuación de la gravedad de la lesión (ISS), intencionalidad, mecanismo, tiempos de asistencia, complicaciones evolutivas y mortalidad. Resultados Ingresaron un total de 188 pacientes (46,8% de activación EATG), edad mediana de 52 (37-64) años (activados 47 (27-62) vs. no activados 55 (42-67) p = 0,023), varones 84,0%. No diferencias en la mortalidad según activación. El modelo logístico encuentra como factores: la atención (16,6 [2,1-13,2]) e intubación prehospitalaria (4,2 [1,8-9,8]) y, la lesión grave de extremidades inferiores (4,4 [1,6-12,3]). Padecer una caída accidental (0,2 [0,1-0,6]) hace menos probable la activación. El modelo CART selecciona el tipo de mecanismo del traumatismo y es capaz de separar los traumatismos de alta y baja energía. Conclusiones Los factores asociados con activación del ETAG fueron la atención prehospitalaria, requerir intubación previa, mecanismos de alta energía y lesiones graves de extremidades inferiores. Menores tiempos de asistencia si activación sin influir en la mortalidad. Debemos mejorar la activación en pacientes mayores con traumatismos de baja energía y sin atención prehospitalaria (AU)

Objective To analyse the factors associated with the activation of the severe trauma care team (STAT) in patients admitted to the ICU, to measure its impact on care times, and to analyse the groups of patients according to activation and level of anatomical involvement. Design Prospective cohort study of severe trauma admitted to the ICU. From June 2017 to May 2019. Risk factors for the activation of the STAT analysed with logistic regression and CART type classification tree. Setting Second level hospital ICU. Patients Patients admitted consecutively. Interventions No. Main variables of interest STAT activation, demographic variables, injury severity (ISS), intentionality, mechanism, assistance times, evolutionary complications, and mortality. Results A total of 188 patients were admitted (46.8% of STAT activation), median age of 52 (37–64) years (activated 47 (27–62) vs. not activated 55 (42–67), p = 0.023), males 84.0%. No difference in mortality according to activation. The logistic model finds as factors: care (16.6 (2.1–13.2)) and prehospital intubation (4.2 (1.8–9.8)) and severe lower extremity injury (4.4 (1.6–12.3)). Accidental fall (0.2 (0.1–0.6)) makes activation less likely. The CART model selects the type of trauma mechanism and can separate high and low energy trauma. Conclusions Factors associated with STAT activation were prehospital care, requiring prior intubation, high-energy mechanisms, and severe lower extremity injuries. Shorter care times if activated without influencing mortality. We must improve activation in older patients with low-energy trauma and without prehospital care (AU)