Revisiting liver metabolism through acetyl-CoA carboxylase inhibition.

Liver-targeted acetyl-coenzyme A (CoA) carboxylase (ACC) inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD) trials reveal notable secondary effects: hypertriglyceridemia and altered glucose metabolism, paradoxically with reduced hepatic steatosis. In their study, Deja et al. explored how hepatic ACC influences metabolism using different pharmacological and genetic methods, coupled with targeted metabolomics and stable isotope-based tracing techniques.

Myosin II regulatory light chain phosphorylation and formin availability modulate cytokinesis upon changes in carbohydrate metabolism.

Cytokinesis, the separation of daughter cells at the end of mitosis, relies in animal cells on a contractile actomyosin ring (CAR) composed of actin and class II myosins, whose activity is strongly influenced by regulatory light chain (RLC) phosphorylation. However, in simple eukaryotes such as the fission yeast Schizosaccharomyces pombe, RLC phosphorylation appears dispensable for regulating CAR dynamics. We found that redundant phosphorylation at Ser35 of the S. pombe RLC homolog Rlc1 by the p21-activated kinases Pak1 and Pak2, modulates myosin II Myo2 activity and becomes essential for cytokinesis and cell growth during respiration. Previously, we showed that the stress-activated protein kinase pathway (SAPK) MAPK Sty1 controls fission yeast CAR integrity by downregulating formin For3 levels (Gómez-Gil et al., 2020). Here, we report that the reduced availability of formin For3-nucleated actin filaments for the CAR is the main reason for the required control of myosin II contractile activity by RLC phosphorylation during respiration-induced oxidative stress. Thus, the restoration of For3 levels by antioxidants overrides the control of myosin II function regulated by RLC phosphorylation, allowing cytokinesis and cell proliferation during respiration. Therefore, fine-tuned interplay between myosin II function through Rlc1 phosphorylation and environmentally controlled actin filament availability is critical for a successful cytokinesis in response to a switch to a respiratory carbohydrate metabolism.

cAMP-Protein kinase A and stress-activated MAP kinase signaling mediate transcriptional control of autophagy in fission yeast during glucose limitation or starvation.

Macroautophagy/autophagy is an essential adaptive physiological response in eukaryotes induced during nutrient starvation, including glucose, the primary immediate carbon and energy source for most cells. Although the molecular mechanisms that induce autophagy during glucose starvation have been extensively explored in the budding yeast Saccharomyces cerevisiae, little is known about how this coping response is regulated in the evolutionary distant fission yeast Schizosaccharomyces pombe. Here, we show that S. pombe autophagy in response to glucose limitation relies on mitochondrial respiration and the electron transport chain (ETC), but, in contrast to S. cerevisiae, the AMP-activated protein kinase (AMPK) and DNA damage response pathway components do not modulate fission yeast autophagic flux under these conditions. In the presence of glucose, the cAMP-protein kinase A (PKA) signaling pathway constitutively represses S. pombe autophagy by downregulating the transcription factor Rst2, which promotes the expression of respiratory genes required for autophagy induction under limited glucose availability. Furthermore, the stress-activated protein kinase (SAPK) signaling pathway, and its central mitogen-activated protein kinase (MAPK) Sty1, positively modulate autophagy upon glucose limitation at the transcriptional level through its downstream effector Atf1 and by direct in vivo phosphorylation of Rst2 at S292. Thus, our data indicate that the signaling pathways that govern autophagy during glucose shortage or starvation have evolved differently in S. pombe and uncover the existence of sophisticated and multifaceted mechanisms that control this self-preservation and survival response.

Socio-demographic inequalities and excess non-COVID-19 mortality during the COVID-19 pandemic: a data-driven analysis of 1 069 174 death certificates in Mexico.

BACKGROUND: In 2020, Mexico experienced one of the highest rates of excess mortality globally. However, the extent of non-COVID deaths on excess mortality, its regional distribution and the association between socio-demographic inequalities have not been characterized. METHODS: We conducted a retrospective municipal and individual-level study using 1 069 174 death certificates to analyse COVID-19 and non-COVID-19 deaths classified by ICD-10 codes. Excess mortality was estimated as the increase in cause-specific mortality in 2020 compared with the average of 2015-2019, disaggregated by primary cause of death, death setting (in-hospital and out-of-hospital) and geographical location. Correlates of individual and municipal non-COVID-19 mortality were assessed using mixed effects logistic regression and negative binomial regression models, respectively. RESULTS: We identified a 51% higher mortality rate (276.11 deaths per 100 000 inhabitants) compared with the 2015-2019 average period, largely attributable to COVID-19. Non-COVID-19 causes comprised one-fifth of excess deaths, with acute myocardial infarction and type 2 diabetes as the two leading non-COVID-19 causes of excess mortality. COVID-19 deaths occurred primarily in-hospital, whereas excess non-COVID-19 deaths occurred in out-of-hospital settings. Municipal-level predictors of non-COVID-19 excess mortality included levels of social security coverage, higher rates of COVID-19 hospitalization and social marginalization. At the individual level, lower educational attainment, blue-collar employment and lack of medical care assistance prior to death were associated with non-COVID-19 deaths. CONCLUSION: Non-COVID-19 causes of death, largely chronic cardiometabolic conditions, comprised up to one-fifth of excess deaths in Mexico during 2020. Non-COVID-19 excess deaths occurred disproportionately out-of-hospital and were associated with both individual- and municipal-level socio-demographic inequalities.

Comprehensive Evaluation of the Impact of Sociodemographic Inequalities on Adverse Outcomes and Excess Mortality During the Coronavirus Disease 2019 (COVID-19) Pandemic in Mexico City.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic in Mexico City has been sharp, as several social inequalities at all levels coexist. Here we conducted an in-depth evaluation of the impact of individual and municipal-level social inequalities on the COVID-19 pandemic in Mexico City. METHODS: We analyzed suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, from the Mexico City Epidemiological Surveillance System from 24 February 2020 to 31 March 2021. COVID-19 outcomes included rates of hospitalization, severe COVID-19, invasive mechanical ventilation, and mortality. We evaluated socioeconomic occupation as an individual risk, and social lag, which captures municipal-level social vulnerability, and urban population density as proxies of structural risk factors. Impact of reductions in vehicular mobility on COVID-19 rates and the influence of risk factors were also assessed. Finally, we assessed discrepancies in COVID-19 and non-COVID-19 excess mortality using death certificates from the general civil registry. RESULTS: We detected vulnerable groups who belonged to economically unfavored sectors and experienced increased risk of COVID-19 outcomes. Cases living in marginalized municipalities with high population density experienced greater risk for COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts modified by social lag and urban population density. Finally, we report an under-registry of COVID-19 deaths along with an excess mortality closely related to marginalized and densely populated communities in an ambulatory setting. This could be attributable to a negative impact of modified hospital admission criteria during the pandemic. CONCLUSIONS: Socioeconomic occupation and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.

Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus.

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe's CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

Unequal Impact of Structural Health Determinants and Comorbidity on COVID-19 Severity and Lethality in Older Mexican Adults: Considerations Beyond Chronological Aging.

BACKGROUND: COVID-19 has had a disproportionate impact on older adults. Mexico's population is younger, yet COVID-19's impact on older adults is comparable to countries with older population structures. Here, we aim to identify health and structural determinants that increase susceptibility to COVID-19 in older Mexican adults beyond chronological aging. METHODS: We analyzed confirmed COVID-19 cases in older adults using data from the General Directorate of Epidemiology of Mexican Ministry of Health. We modeled risk factors for increased COVID-19 severity and mortality, using mixed models to incorporate multilevel data concerning healthcare access and marginalization. We also evaluated structural factors and comorbidity profiles compared to chronological age for COVID-19 mortality risk prediction. RESULTS: We analyzed 20 804 confirmed SARS-CoV-2 cases in adults aged 60 and older. Male sex, smoking, diabetes, and obesity were associated with pneumonia, hospitalization, and intensive care unit (ICU) admission in older adults, CKD and COPD were associated with hospitalization. High social lag indexes and access to private care were predictors of COVID-19 severity and mortality. Age was not a predictor of COVID-19 severity in individuals without comorbidities and combination of structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age alone. COVID-19 baseline lethality hazards were heterogeneously distributed across Mexican municipalities, particularly when comparing urban and rural areas. CONCLUSIONS: Structural factors and comorbidity explain excess risk for COVID-19 severity and mortality over chronological age in older Mexican adults. Clinical decision-making related to COVID-19 should focus away from chronological aging onto more a comprehensive geriatric care approach.

Predicting Mortality Due to SARS-CoV-2: A Mechanistic Score Relating Obesity and Diabetes to COVID-19 Outcomes in Mexico.

BACKGROUND: The SARS-CoV-2 outbreak poses a challenge to health care systems due to its high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity, and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of the Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19-related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among the 177 133 subjects at the time of writing this report (May 18, 2020), we observed 51 633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, chronic obstructive pulmonary disease, advanced age, hypertension, immunosuppression, and chronic kidney disease (CKD); we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for intensive care unit admission and intubation. Our predictive score for COVID-19 lethality included age ≥ 65 years, diabetes, early-onset diabetes, obesity, age < 40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (C-statistic = 0.823). CONCLUSIONS: Here, we propose a mechanistic approach to evaluate the risk for complications and lethality attributable to COVID-19, considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first-contact scenario.

Effects of physical activity interventions on the body mass index of children and adolescents in Latin America: a protocol for a systematic review and meta-analysis.

INTRODUCTION: In Latin America, the number of children and adolescents who are overweight or obese has significantly increased in recent decades, and this situation has become a major public health concern. To address this problem, several intervention programmes, based on factors such as physical activity and nutrition, have been implemented, and body mass index (BMI) has been widely used as a means of measuring the impact of such interventions. Although some Latin America-based systematic reviews have been performed, there have been no previous meta-analyses of findings regarding the effect of physical activity interventions on BMI. Thus, the objective of the systematic review and meta-analysis will be to provide an up-to-date synthesis of the effects of physical activity interventions on BMI of Latin American children and adolescents aged 4-18 years. METHODS AND ANALYSIS: This systematic review and meta-analysis protocol is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. The literature search will involve MEDLINE, EMBASE, Cochrane Library, Web of Science and Scielo for articles published up to July 2019. This search will include randomised controlled trials (RCTs), non-randomised experimental studies and single-arm pre-post studies. Further, the Cochrane Collaboration's tool for RCT studies and the Quality Assessment Tool for Quantitative Studies for non-randomised experimental and single-arm pre-post studies will be used to assess the risk of bias among the studies included in the systematic review. For the meta-analysis, the statistical program STATA V.14 will be used, and standardised mean differences are calculated as the primary outcomes. Subgroup analyses will then be performed based on the characteristics of the interventions and populations included in the studies examined. ETHICS AND DISSEMINATION: This systematic review protocol is designed to provide updated evidence regarding the effects of physical activity interventions on the Latin American population; such evidence may be useful for institutions responsible for the development of public health policies and for those tasked with implementing such interventions among children and adolescents in Latin America. The results should be disseminated through publication in a peer-reviewed journal. Since the data used in systematic reviews of this type will be extracted exclusively from published studies, approval from an ethics committee will not be required. PROSPERO REGISTRATION NUMBER: CRD42019077702.

Utilidad de un material didáctico sobre Investigación Cualitativa en Salud / Usefulness of a didactic material on Qualitative Investigation in Health

Se realizó un estudio descriptivo y transversal de 139 estudiantes de segundo año de la carrera Licenciatura en Enfermería, pertenecientes a la Facultad de Enfermería-Tecnología de la Salud de Santiago de Cuba, desde septiembre de 2017 hasta enero de 2018, a fin de evaluar la utilidad de un material didáctico sobre Investigación Cualitativa como herramienta de apoyo a la asignatura Elementos de Investigación Cualitativa en Salud. Se obtuvo un elevado nivel de aceptación en los estudiantes, quienes confirmaron la claridad con que se exponen los contenidos, el nivel de profundidad y la importancia de contar con un texto que ejemplifique y vincule el contenido de metodología de la investigación con situaciones de su práctica diaria. Este material favoreció la calidad del proceso de enseñanza - aprendizaje, dada en la promoción alcanzada, que resultó cualitativamente superior a la de cursos anteriores.

A descriptive and cross-sectional study of 139 students of 2nd year of Licentiate in Nursing, belonging to the Health Nursing-Technology Faculty in Santiago de Cuba was carried out from September, 2017 to January, 2018, in order to evaluate the usefulness of a didactic material on Qualitative Investigation as a support tool to the subject Elements of Qualitative Investigation in Health. A high level of acceptance was obtained in the students who confirmed the clarity with which the contents and their quality are exposed and the importance of having a text that exemplifies and links the content of the investigation methodology with situations of the daily practice. This material favored the quality of the teaching - learning process, given the high marks, which were qualitatively higher to those of previous courses.

Utilidad de un material didáctico sobre Investigación Cualitativa en Salud / Usefulness of a didactic material on Qualitative Investigation in Health

Se realizó un estudio descriptivo y transversal de 139 estudiantes de segundo año de la carrera Licenciatura en Enfermería, pertenecientes a la Facultad de Enfermería-Tecnología de la Salud de Santiago de Cuba, desde septiembre de 2017 hasta enero de 2018, a fin de evaluar la utilidad de un material didáctico sobre Investigación Cualitativa como herramienta de apoyo a la asignatura Elementos de Investigación Cualitativa en Salud. Se obtuvo un elevado nivel de aceptación en los estudiantes, quienes confirmaron la claridad con que se exponen los contenidos, el nivel de profundidad y la importancia de contar con un texto que ejemplifique y vincule el contenido de metodología de la investigación con situaciones de su práctica diaria. Este material favoreció la calidad del proceso de enseñanza - aprendizaje, dada en la promoción alcanzada, que resultó cualitativamente superior a la de cursos anteriores(AU)

A descriptive and cross-sectional study of 139 students of 2nd year of Licentiate in Nursing, belonging to the Health Nursing-Technology Faculty in Santiago de Cuba was carried out from September, 2017 to January, 2018, in order to evaluate the usefulness of a didactic material on Qualitative Investigation as a support tool to the subject Elements of Qualitative Investigation in Health. A high level of acceptance was obtained in the students who confirmed the clarity with which the contents and their quality are exposed and the importance of having a text that exemplifies and links the content of the investigation methodology with situations of the daily practice. This material favored the quality of the teaching - learning process, given the high marks, which were qualitatively higher to those of previous courses(AU)

Effects of childhood trauma on adult moral decision-making: Clinical correlates and insights from bipolar disorder.

BACKGROUND: Childhood adversity has been shown to exert profound effects on basic psychological processes well into adulthood. Some of these processes, such as those related to reward and emotion, play critical roles in moral decision-making. As a population with high rates of childhood trauma as well as heterogenous clinical presentation, individuals with bipolar disorder (BD) constitute an enriched group in which to examine the correlates of trauma and other clinical variables with moral cognition. METHODS: 62 euthymic BD patients and 27 controls responded to moral dilemma scenarios and completed the Childhood Trauma Questionnaire. RESULTS: Results revealed a main effect of diagnosis on moral decision-making only when both personal force and an intention were required, indicating a more utilitarian style in BD patients relative to controls. Several interesting patterns also emerged regardless of diagnostic status. Higher ratings of physical neglect were significantly associated with higher ratings of acceptability (a utilitarian tendency) across dilemma types, and a similar pattern was observed at the trend level for experiences of emotional neglect. Significant main effects on moral decision-making were also observed for sex, illness duration, and history of psychotic features in the BD sample. LIMITATIONS: The present study is limited by the self-reported nature of the CTQ and by the small number of trials of moral dilemmas. In addition, practical and clinical implications of the moral dilemmas paradigm are limited due to its abstract nature. CONCLUSIONS: Our results indicate that certain clinical features as well as childhood maltreatment (in particular neglect) may significantly impact moral decision making in adult life. Surprisingly, childhood trauma was associated with a more utilitarian style, which is in the opposite direction from previous effects shown in PTSD. Although speculative, our results suggest that there may be a protective quality associated with utilitarian moral decision-making tendencies.

Organizational Learning Strategies and Verbal Memory Deficits in Bipolar Disorder.

BACKGROUND: Verbal memory (VM) impairment is prominent in bipolar disorder (BD) and is linked to functional outcomes. However, the intricacies of VM impairment have not yet been studied in a large sample of BD patients. Moreover, some have proposed VM deficits that may be mediated by organizational strategies, such as semantic or serial clustering. Thus, the exact nature of VM break-down in BD patients is not well understood, limiting remediation efforts. We investigated the intricacies of VM deficits in BD patients versus healthy controls (HCs) and examined whether verbal learning differences were mediated by use of clustering strategies. METHODS: The California Verbal Learning Test (CVLT) was administered to 113 affectively stable BD patients and 106 HCs. We compared diagnostic groups on all CVLT indices and investigated whether group differences in verbal learning were mediated by clustering strategies. RESULTS: Although BD patients showed significantly poorer attention, learning, and memory, these indices were only mildly impaired. However, BD patients evidenced poorer use of effective learning strategies and lower recall consistency, with these indices falling in the moderately impaired range. Moreover, relative reliance on semantic clustering fully mediated the relationship between diagnostic category and verbal learning, while reliance on serial clustering partially mediated this relationship. CONCLUSIONS: VM deficits in affectively stable bipolar patients were widespread but were generally mildly impaired. However, patients displayed inadequate use of organizational strategies with clear separation from HCs on semantic and serial clustering. Remediation efforts may benefit from education about mnemonic devices or "chunking" techniques to attenuate VM deficits in BD. (JINS, 2017, 23, 358-366).

Prevalencia de patología maligna de seno en mujeres mayores de 14 años que consultaron por masa sólida palpable / Prevalence of breast malignancy in women older than forteen years who consulted for solid palpable mass

Objetivo Establecer la prevalencia de la patología maligna en pacientes con masa sólida palpable, sin diagnóstico previo de cáncer de seno en dos hospitales de Bogotá, Colombia. Materiales y métodos Estudio descriptivo retrospectivo entre marzo de 2010 y febrero de 2013 en los hospitales de San José e Infantil Universitario de San José, Bogotá D. C., Colombia. Se incluyeron mujeres mayores de 14 años que consultaron por masa sólida palpable sin diagnóstico previo de cáncer de seno, corroborada por examen físico; no se consideró ningún criterio de exclusión. Los datos se recolectaron de las historias clínicas y se llevaron a un formato creado por los investigadores. El programa estadístico utilizado fue Stata 13. Resultados Se confirmó la masa en 342 pacientes por examen clínico, en 307 pacientes con resultado de biopsia. La prevalencia de la patología maligna fue 12,2% y benigna 71,66%. Discusión La prevalencia de patología maligna por masa palpable fue menor que los datos reportados a nivel mundial, siendo el tumor más frecuente el carcinoma ductal infiltrante en un 87%, carcinoma lobulillar infiltrante en 6,4%), con estadio clínico IIA y BI-RADS 4 A (ecografía) y BI-RADS 4B (mamografía).

Objective To determine the prevalence rate of malignancy in patients with no prior breast cancer diagnosis who consulted for a solid palpable mass in two hospitals in Bogotá, Colombia. Materials and methods A descriptive retrospective study conducted between March 2010 and February 2013 at San José and Infantil Universitario de San José hospitals in Bogotá D. C., Colombia. Women 14 years or older with no prior breast cancer diagnosis who consulted for a palpable solid mass, confirmed by physical exam, were included. No exclusion criteria were considered. Data was collected from the clinical records and included in a format created by the researchers. Stata 13 was used for data analysis. Results The mass was confirmed by physical exam in 342 patients and by a biopsy in 307 patients. The prevalence rate for malignancy was 12.2% and for benign masses 71.66%. Discussion Our prevalence of breast cancer associated with a palpable mass was less than worldwide reported prevalence. The most frequent malignancy was invasive ductal carcinoma in 87% and invasive lobular carcinoma in 6.4% in stage IIA and BI-RADS 4A ultrasound category and BI-RADS 4B mammogram category.

The effects of cigarette smoking behavior and psychosis history on general and social cognition in bipolar disorder.

OBJECTIVES: Several studies have documented the prevalence and effects of cigarette smoking on cognition in psychotic disorders; fewer have focused on bipolar disorder (BD). Cognitive and social dysfunction are common in BD, and the severity of these deficits may be related both to illness features (e.g., current symptoms, psychosis history) and health-related behaviors (e.g., smoking, alcohol use). The current study assessed the influence of cigarette smoking on general and social cognition in a BD cohort, accounting for illness features with a focus on psychosis history. METHODS: We assessed smoking status in 105 euthymic patients with BD, who completed a comprehensive battery including social (facial affect recognition, emotional problem-solving, and theory of mind) and general (the MATRICS Consensus Cognitive Battery and executive functioning) cognitive measures. We compared smokers vs nonsmokers on cognitive performance and tested for the effects of psychosis history, premorbid intellectual functioning, substance use, and current affective symptoms. RESULTS: Within the nonpsychotic subgroup with BD (n=45), smokers generally outperformed nonsmokers; by contrast, for subjects with BD with a history of psychosis (n=41), nonsmokers outperformed smokers. This pattern was noted more globally using a general composite cognitive score and on social/affective measures assessing patients' ability to identify emotions of facial stimuli and solve emotional problems. CONCLUSIONS: Cigarette smoking differentially affects performance on both general and social cognition in patients with BD as a function of psychosis history. These results suggest that there may be at least partially divergent underlying neurobiological causes for cognitive dysfunction in patients with BD with and without psychosis.

Coping strategies and real-world functioning in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) patients encounter significant life adversity, which has contributed to bipolar disorder being a leading cause of disability worldwide. Studies suggest BD patients have more maladaptive coping strategies, some of which can impact their illness course. Yet research on which coping strategies most influence disability is lacking. Such research could inform cognitive-behavioral targets to improve functional outcomes. Thus, we sought to identify relations between coping strategies and real-world function in BD. METHODS: In 92 affectively-stable BD outpatients, we measured coping strategies via the Brief COPE, real-world disability via the World Health Organization Disability Assessment Schedule, current symptoms, illness chronicity, and neurocognitive functioning via the MATRICS. Multiple regression analysis served to identify the neurocognitive domains predictive of disability for entry into subsequent analyses. Multiple regressions assessed how adaptive and maladaptive coping strategies influenced disability. RESULTS: Only one neurocognitive domain, verbal learning, significantly predicted disability and was included in subsequent analyses. Maladaptive coping significantly predicted disability while adaptive coping did not. Behavioral disengagement (giving up) and self-blame were the only remaining predictors of disability, after controlling for age, sex, illness chronicity, current symptoms, and neurocognitive functioning. LIMITATIONS: The study was limited by the use of a self-report disability measure and a brief-form coping scale. CONCLUSIONS: Results suggest that giving up and self-blame are significant predictors of real-world functioning beyond sub-threshold depressive symptoms. Our results in BD expand upon recent schizophrenia studies suggesting that defeatist beliefs negatively influence functional outcomes across the range of major psychiatric disorders.

Respuesta: La paradoja del tabaquismo: fumar o no fumar / Reply: Smoking paradox: smoking or not smoking

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Plasma biomarkers distinguish non-small cell lung cancer from asthma and differ in men and women.

BACKGROUND: Lung cancer (LC) is the leading cause of deaths caused by cancer worldwide. A diagnostic test for LC is needed for monitoring high-risk populations. PATIENTS AND METHODS: Fifty-seven markers were measured using multiplex immunoassays of plasma of patients with non-small cell lung cancer (NSCLC); (245 men, 114 women, 1 unknown), asthma (67 men, 111 women, 2 unknown) and of healthy controls (165 men, 122 women, 1 unknown). Mass spectrometry was used for biomarker discovery. A support vector machine (SVM) was used for data analysis. RESULTS: When all biomarkers and both genders were co-analyzed, SVM classified NSCLC and asthma with an accuracy of 0.94. Restricting to NSCLC versus healthy using best subsets of variables (males: epidermal growth factor (EGF), interleukin-8 (IL-8), soluble Fas (sFas), matrix metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1); females: EGF, soluble cluster of differentiation 40 (sCD40) ligand, IL-8) yielded sensitivity and specificity of 1. Expression of eleven mass spectrometric biomarkers differed between pathologies. CONCLUSION: Significant inter-pathology and gender differences between biomarkers may improve diagnosis of LC.

La paradoja del tabaco en el síndrome coronario agudo sin elevación del ST / Smoking paradox in acute coronary syndrome without st-segment elevation

Fundamento y objetivo: Aunque el tabaco es un conocido factor de riesgo cardiovascular, se ha descrito que en los pacientes ingresan por un infarto de miocardio parece observarse un mejor pronóstico, a corto plazo, en los que tienen antecedente de tabaquismo, lo que se conoce como “paradoja del tabaco”. El propósito de nuestro estudio es comprobar si este fenómeno se da en los pacientes con síndrome coronario agudo sin elevación del ST (SCASEST) y qué factores contribuyen a explicarlo.Pacientes y método: Se analizaron 563 pacientes consecutivos que ingresaron por SCASEST en la Unidad Coronaria de nuestro centro desde enero de 2005 hasta diciembre de 2006. Se analizaron las características clínicas y angiográficas y su relación con las complicaciones y pronóstico intrahospitalario. Resultados: Un total de 155 pacientes eran fumadores (27,53%). Lo pacientes fumadores eran más jóvenes de media que los no fumadores, con más frecuencia fueron varones, presentaban menos factores de riesgo cardiovascular y con mayor frecuencia estaban en clase Killip I (91,6 frente a 79,3%). Los pacientes fumadores tuvieron con menor frecuencia el evento combinado de muerte, reinfarto o Killip IV (6,5 frente a 13,6%, odds ratio 0,439, intervalo de confianza del 95% 0,218 a 0,885, p=0,018). Esta relación perdió la significación estadística al ajustar mediante regresión logística en la que se incluyeron los datos clínicos y angiográficos significativos.Conclusiones: Nuestro estudio confirma la existencia de la “paradoja del tabaco” en el SCASEST, pero queda explicada por la menor prevalencia de infarto previo, diabetes mellitus o enfermedad multivaso. Es fundamental aconsejar a los fumadores el abandono del tabaco (AU)

Background and objective: Although smoking habit is a well-known cardiovascular risk factor, it has been described that smokers admitted because of myocardial infarction have better prognosis than non smoker patients, which is known as “the smoking paradox”. The purpose of our work is to investigate whether this phenomenon occurs among patients admitted because of acute coronary syndrome without ST-segment elevation (NSTACS), and which factors help to explain it. Patients and Methods: We analysed 563 consecutive patients admitted because of NSTACS on the Coronary Unit of our hospital from January 2005 to December 2006. We analysed clinic and angiographic characteristics and their relationship with in-hospital complications and prognosis. Results: 155 Patients were smokers (27,53%). Smoker patients were younger, more often male, had less risk factors, and more often had a Killip I class at admission (91.6% vs. 79.3%). They had less commonly the combined endpoint of death, reinfarction or Killip Class IV (6.5 vs 13.6%, odds ratio 0,439, confidence interval 0,218 a 0,885, P=.018). This relationship was lost after adjusting to other significant clinical and angiographic data by logistic regression. Conclusions: Our study confirms the “smoking paradox” amongst NSTACS patients, which is explained by the lower prevalence of previous myocardial infarction, diabetes or multivessel disease. It is essential to recommend quitting the smoking habites (AU)

[Smoking paradox in acute coronary syndrome without ST-segment elevation]. / La paradoja del tabaco en el síndrome coronario agudo sin elevación del ST.

BACKGROUND AND OBJECTIVE: Although smoking habit is a well-known cardiovascular risk factor, it has been described that smokers admitted because of myocardial infarction have better prognosis than non smoker patients, which is known as "the smoking paradox". The purpose of our work is to investigate whether this phenomenon occurs among patients admitted because of acute coronary syndrome without ST-segment elevation (NSTACS), and which factors help to explain it. PATIENTS AND METHODS: We analysed 563 consecutive patients admitted because of NSTACS on the Coronary Unit of our hospital from January 2005 to December 2006. We analysed clinic and angiographic characteristics and their relationship with in-hospital complications and prognosis. RESULTS: 155 Patients were smokers (27.53%). Smoker patients were younger, more often male, had less risk factors, and more often had a Killip I class at admission (91.6% vs. 79.3%). They had less commonly the combined endpoint of death, reinfarction or Killip Class IV (6.5 vs 13.6%, odds ratio 0.439, confidence interval 0.218 a 0.885, P=.018). This relationship was lost after adjusting to other significant clinical and angiographic data by logistic regression. CONCLUSIONS: Our study confirms the "smoking paradox" amongst NSTACS patients, which is explained by the lower prevalence of previous myocardial infarction, diabetes or multivessel disease. It is essential to recommend quitting the smoking habit.