RESUMEN

PURPOSE OF REVIEW: We review the role of uromodulin, a protein exclusively expressed in the kidney, in blood pressure regulation and hypertension. RECENT FINDINGS: The last few years have seen a shift of focus from genetic association to mendelian randomisation and uromodulin-salt interaction studies, thus confirming the causal role of uromodulin in blood pressure regulation and hypertension. This work has been complemented by phenome-wide association studies in a wider range of ethnicities. Important recent molecular work elucidated uromodulin trafficking and secretion and provided more insights into the pathophysiological roles of circulating and urinary uromodulin. Uromodulin has a causal role in blood pressure regulation and hypertensin. Recent studies show utility of the uromodulin as a biomarker and a possible precision medicine application based on genetically determined differential responses to loop diuretics.

RESUMEN

Introduction: Current vaccines against COVID-19 administered via parenteral route have limited ability to induce mucosal immunity. There is a need for an effective mucosal vaccine to combat SARS-CoV-2 virus replication in the respiratory mucosa. Moreover, sex differences are known to affect systemic antibody responses against vaccines. However, their role in mucosal cellular responses against a vaccine remains unclear and is underappreciated. Methods: We evaluated the mucosal immunogenicity of a booster vaccine regimen that is recombinant protein-based and administered intranasally in mice to explore sex differences in mucosal humoral and cellular responses. Results: Our results showed that vaccinated mice elicited strong systemic antibody (Ab), nasal, and bronchiole alveolar lavage (BAL) IgA responses, and local T cell immune responses in the lung in a sex-biased manner irrespective of mouse genetic background. Monocytes, alveolar macrophages, and CD103+ resident dendritic cells (DCs) in the lungs are correlated with robust mucosal Ab and T cell responses induced by the mucosal vaccine. Discussion: Our findings provide novel insights into optimizing next-generation booster vaccines against SARS-CoV-2 by inducing spike-specific lung T cell responses, as well as optimizing mucosal immunity for other respiratory infections, and a rationale for considering sex differences in future vaccine research and vaccination practice.

Asunto(s)

Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Mucosa , Inmunogenicidad Vacunal , SARS-CoV-2 , Vacunas de Subunidad , Animales , Femenino , Ratones , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Masculino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Pulmón/inmunología , Pulmón/virología , Linfocitos T/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Ratones Endogámicos C57BL , Administración Intranasal , Factores Sexuales , Inmunoglobulina A/inmunología , Células Dendríticas/inmunología , Inmunización Secundaria , Inmunidad Humoral

RESUMEN

(1) Objectives: This study aimed to assess the 5-year prevalence and clinical profile of attention deficit hyperactive disorder (ADHD) among adult patients seeking care in a tertiary care hospital in Oman. (2) Methods: The data were analysed using descriptive and inferential statistics and standardised prevalence estimates were calculated. (3) Results: Of the 39,881 hospital visits, 1.77% were made by adults with ADHD. This is equivalent to 17.8 visits per 1000 outpatients. The year 2021 saw the highest prevalence among the five years considered, while 2020 had the lowest prevalence. Although the age distribution indicated that the age group 'under 20' had the highest prevalence, the gender distribution showed that ADHD was more common among adult men. Among the various subtypes of ADHD, inattention was the most common. (4) Conclusions: This study specifically compared the prevalence and associated factors between an adult cohort with ADHD and those other psychiatric clinic attendees during the same period. The study offers important information on the prevalence and clinical profile of adults with ADHD in the population under consideration.

Asunto(s)

Trastorno por Déficit de Atención con Hiperactividad , Centros de Atención Terciaria , Humanos , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Masculino , Prevalencia , Adulto , Femenino , Omán/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Adolescente , Anciano

RESUMEN

INTRODUCTION: Due to the important functions of the mesencephalon, knowledge of its morphometric characteristics in a healthy population is important for any pathological diagnosis. The aim of this study was to determine the specific morphometric values of the mesencephalon in a healthy Turkish population. METHODS: Magnetic resonance (MR) images of 184 subjects (98 females, 86 males) with a mean age of 47.33 years (range 18 to 85 years) were included in the study. Then, parameter measurements were performed on 1.5 T MR images, and MicroDicom Digital Imaging and Communications in Medicine (DICOM) viewer 2022.1 (MicroDicom Ltd., Sofia, Bulgaria) software program was used for the measurements. RESULTS: The mean sagittal diameter of the right cerebral peduncle was 17.17±2.03 mm, the mean cross-sectional area of the right cerebral peduncle was 171.75±32.81 mm2, the mean transverse diameter of the left cerebral peduncle was 16.60±2.32 mm, sagittal diameter of tectum and tegmentum 17.01±1.57 mm, the cross-sectional area of tectum and tegmentum 223.40±27.37 mm2 and pontomesencephalic angle 52.03°±10.61°, while in males these values were 18.26±2.38 mm, 182.61±38.57 mm2, 17.39±2.57 mm, 17.76±1.90 mm, 237.20±35.94 mm2 and 56.77°±9.78°, respectively. Except for the mamillopontine distance, there was a statistically significant difference between genders in the other parameters (p<0.05). CONCLUSION: In conclusion, the findings related to the mesencephalon obtained in this study are presented for the first time in a healthy Turkish population. Especially, the cerebral peduncle cross-sectional area, tectum and tegmentum cross-sectional area, and cerebral peduncle transverse diameter can be evaluated clinically. We believe that knowledge of these values will guide specialists and radiologists in the diagnosis of any pathologic condition. Furthermore, the pontomesencephalic angle and mamillopontine distance have been identified as potentially useful landmarks in the diagnosis of intracranial hypotension and hydrocephalus. In particular, these angles can be measured in patient groups and may be a potential landmark in making an alternative diagnosis.

RESUMEN

Obesity and metabolic diseases are rising among women of reproductive age, increasing offspring metabolic risk. Maternal nutritional interventions during lactation present an opportunity to modify offspring outcomes. We previously demonstrated in mice that adult male offspring have metabolic impairments and increased adipose tissue macrophages (ATM) when dams are fed high fat diet (HFD) during the postnatal lactation window (HFD PN). We sought to understand the effect of HFD during lactation on early-life inflammation. HFD PN offspring were evaluated at postnatal day 16 to 19 for tissue weight and gene expression. Profiling of adipose tissue and bone marrow immune cells was conducted through lipidomics, in vitro myeloid colony forming unit assays, and flow cytometry. HFD PN mice had more visceral gonadal white adipose tissue (GWAT) and subcutaneous fat. Adipose tissue RNA sequencing demonstrated enrichment of inflammation, chemotaxis, and fatty acid metabolism and concordant changes in GWAT lipidomics. Bone marrow (BM) of both HFD PN male and female offspring had increased monocytes (CD45+Ly6G-CD11b+CD115+) and B cells (CD45+Ly6G-CD11b-CD19+). Similarly, serum from HFD PN offspring enhanced in vitro BM myeloid colonies in a toll-like receptor 4-dependent manner. We identified that male HFD PN offspring had increased GWAT pro-inflammatory CD11c+ ATMs (CD45+CD64+). Maternal exposure to HFD alters milk lipids enhancing adiposity and myeloid inflammation even in early life. Future studies are needed to understand the mechanisms driving this pro-inflammatory state of both BM and ATMs, the causes of the sexually dimorphic phenotypes, and the feasibility of intervening in this window to improve metabolic health.

Asunto(s)

Dieta Alta en Grasa , Obesidad , Femenino , Masculino , Ratones , Animales , Humanos , Dieta Alta en Grasa/efectos adversos , Obesidad/etiología , Lactancia , Inflamación , Exposición Materna , Fenómenos Fisiologicos Nutricionales Maternos

RESUMEN

The underlying biological mechanisms that contribute to the heterogeneity of major depressive disorder (MDD) presentation remain poorly understood, highlighting the need for a conceptual framework that can explain this variability and bridge the gap between animal models and clinical endpoints. Here, we hypothesize that comparative analysis of molecular data from different experimental systems of chronic stress, and MDD has the potential to provide insight into these mechanisms and address this gap. Thus, we compared transcriptomic profiles of brain tissue from postmortem MDD subjects and from mice exposed to chronic variable stress (CVS) to identify orthologous genes. Ribosomal protein genes (RPGs) were down-regulated, and associated ribosomal protein (RP) pseudogenes were up-regulated in both conditions. A seeded gene co-expression analysis using altered RPGs common between the MDD and CVS groups revealed that down-regulated RPGs homeostatically regulated the synaptic changes in both groups through a RP-pseudogene-driven mechanism. In vitro analysis demonstrated that the RPG dysregulation was a glucocorticoid-driven endocrine response to stress. In silico analysis further demonstrated that the dysregulation was reversed during remission from MDD and selectively responded to ketamine but not to imipramine. This study provides the first evidence that ribosomal dysregulation during stress is a conserved phenotype in human MDD and chronic stress-exposed mouse. Our results establish a foundation for the hypothesis that stress-induced alterations in RPGs and, consequently, ribosomes contribute to the synaptic dysregulation underlying MDD and chronic stress-related mood disorders. We discuss the role of ribosomal heterogeneity in the variable presentations of depression and other mood disorders.

RESUMEN

BACKGROUND: Age-, gender- and body site-specific values of thermal Quantitative Sensory Testing (QST) measures have not yet been reported using the novel and cheap device 'Q-sense'. Here, we aimed to assess normative values of Q-sense-derived parameters in a representative Italian population. METHODS: QST parameters were measured in 84 healthy participants (42 males; aged 20-76 years) equally distributed into three age groups (18-39, 40-59 and 60-80 years). We explored the Warm and the Cold Detection Thresholds (WDT and CDT, respectively) with the method of limits (MLI) and the method of levels (MLE), and the Heat Pain Threshold (HPT) with the MLI. We tested the trigeminal supraorbital region, the hand thenar, and the foot dorsum on the right body side. RESULTS: We calculated non-parametric reference limits (2.5-97.5th) according to age, gender and tested site. All QST measures were affected by age, gender and tested site. In the extra-trigeminal body sites, females showed lower WDT and higher CDT, while males had higher HPT. Worse sensory discriminative abilities and increased HPT values were found in people aged over 40 on the foot. Age-related differences were more evident with the reaction time-dependent MLI vs. MLE paradigm. CONCLUSIONS: Demographic characteristics must be considered when QST is used in the clinical setting. The definition of reference limits for sensory testing with the Q-sense herein provided can pave the way towards a more widespread use of thermal QST for diagnosing small fiber neuropathy and for identifying patients' profiles in different chronic pain syndromes.

Asunto(s)

Umbral del Dolor , Dolor , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Umbral Sensorial/fisiología , Valores de Referencia , Dimensión del Dolor/métodos

Asunto(s)

Ejercicio Físico , Músculos , Presión Sanguínea , Ejercicio Físico/fisiología , Sistema Nervioso Simpático/fisiología , Fuerza de la Mano/fisiología , Frecuencia Cardíaca/fisiología , Músculo Esquelético

RESUMEN

BACKGROUND: Most epidemiological studies show a decrease of internalizing disorders at older ages, but it is unclear how the prevalence exactly changes with age, and whether there are different patterns for internalizing symptoms and traits, and for men and women. This study investigates the impact of age and sex on the point prevalence across different mood and anxiety disorders, internalizing symptoms, and neuroticism. METHODS: We used cross-sectional data on 146 315 subjects, aged 18-80 years, from the Lifelines Cohort Study, a Dutch general population sample. Between 2012 and 2016, five current internalizing disorders - major depression, dysthymia, generalized anxiety disorder, social phobia, and panic disorder - were assessed according to DSM-IV criteria. Depressive symptoms, anxiety symptoms, neuroticism, and negative affect (NA) were also measured. Generalized additive models were used to identify nonlinear patterns across age, and to investigate sex differences. RESULTS: The point prevalence of internalizing disorders generally increased between the ages of 18 and 30 years, stabilized between 30 and 50, and decreased after age 50. The patterns of internalizing symptoms and traits were different. NA and neuroticism gradually decreased after age 18. Women reported more internalizing disorders than men, but the relative difference remained stable across age (relative risk ~1.7). CONCLUSIONS: The point prevalence of internalizing disorders was typically highest between age 30 and 50, but there were differences between the disorders, which could indicate differences in etiology. The relative gap between the sexes remained similar across age, suggesting that changes in sex hormones around the menopause do not significantly influence women's risk of internalizing disorders.

Asunto(s)

Trastorno Depresivo Mayor , Dinámicas no Lineales , Humanos , Femenino , Masculino , Adolescente , Adulto Joven , Adulto , Prevalencia , Estudios de Cohortes , Estudios Transversales , Trastorno Depresivo Mayor/epidemiología

RESUMEN

AIMS: The evidence for association between cardiovascular health (CVH) metrics and type 2 diabetes mellitus (T2DM) in Chinese population is limited. We explored the association between the number of ideal CVH metrics and risk of incident T2DM in a rural Chinese population. MATERIALS AND METHODS: A total of 12,150 rural Chinese participants (median age 51 years) were enrolled. A Cox proportional-hazards model was used to assess the association between the number of ideal CVH metrics and risk of incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs). We another conducted multiplicative and additive interaction effect between the number of ideal CVH metrics and sex or age on incident T2DM, and subgroup analyses of the association were also conducted by sex and age. RESULTS: During a median of 6.01 years of follow-up, 840 incident cases of T2DM occurred. The number of ideal CVH metrics was negatively associated with risk of incident T2DM (per unit increase: HR = 0.76, 95% CI 0.70-0.82). We also observed both multiplicative and additive interaction effect between lower number of ideal CVH metrics and sex on incident T2DM, and multiplicative interaction effect between lower number of ideal CVH metrics and age on incident T2DM was observed. The association remained statistically significant for both men and women, or participants with age < 65 years. CONCLUSIONS: Increasing number of ideal CVH metrics was associated with reduced risk of incident T2DM, which presented age- and sex-related differential associations.

Asunto(s)

Enfermedades Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Indicadores de Calidad de la Atención de Salud , Factores de Riesgo

RESUMEN

SUMMARY: This paper was aimed to determine the morphometric measurements of cerebellum using MRI in subjects having migraine, ataxia, dementia and vertigo. Three hundred twenty six (326 subjects; 80 migraine subjects; 85 vertigo subjects; 83 dementia subjects; 78 ataxia subjects) subjects ranging from 20 up to 85 years were included in this study. Cerebellum morphometric measurements were taken from subjects having brain MRI in the Radiology Department. The means and standard deviations of the measurements were: Sagittal section cerebellum superior inferior length, 56.21±5.16 mm; sagittal section cerebellum anteroposterior length, 86.36 ±5.36 mm; axial section cerebellum antereoposterior length, 66.53±5.41 mm; axial section bi-cerebellar length, 100.48±5.14 mm; coronal section cerebellum supero-inferior length,53.60±3.84 mm; coronal section bi-cerebellar length, 99.77±6.24 mm in subjects with migraine, whereas the corresponding values were 62.33±8.66 mm; 93.31±9.89 mm; 60.26±7.98 mm; 99.89±6.41 mm; 54.35±4.64 mm; 85.58±14.74 mm in subjects with vertigo, respectively. The same values were found as 58.82±8.34 mm; 86.74±13.22 mm; 58.93±8.89 mm; 97.93±6.07 mm; 50.66±4.92 mm; 84.96±14.93 mm in patients having dementia, respectively, while the same measurements were as 60.83±8.59 mm; 92.18±9.12 mm; 57.76±7.85 mm; 97.71±5.82 mm; 52.48±4.85 mm; 81.49±14.38 mm in ataxia patients, respectively. Also, ages were divided into seven groups as decades. There were found significant difference in all parameters according to sex and ages (p<0.05). The cerebellum morphometry provides important and useful knowledge in terms of comparison of abnormalities clinicians and data will be valuable for the determination of pathologies for clinical disciplines.

---

RESUMEN: Este trabajo tuvo como objetivo determinar las medidas morfométricas del cerebelo mediante resonancia magnética en sujetos con migraña, ataxia, demencia y vértigo. Trescientos veintiseis sujetos (80 con migraña; 85 con vértigo; 83 con demencia y 78 con ataxia) entre los 20 y los 85 años de edad se incluyeron en este estudio. Se tomaron medidas morfométricas del cerebelo de sujetos sometidos a resonancia magnética en el Departamento de Radiología. Las medias y desviaciones estándar de las medidas fueron: sección sagital longitud superoinferior del cerebelo, 56,21±5,16 mm; sección sagital longitud anteroposterior del cerebelo, 86,36 ±5,36 mm; sección axial longitud anteroposterior del cerebelo, 66,53±5,41 mm; sección axial longitud bicerebelosa, 100,48±5,14 mm; sección coronal longitud superoinferior del cerebelo, 53,60±3,84 mm; longitud bicerebelosa de la sección coronal, 99,77±6,24 mm en sujetos con migraña, mientras que los valores correspondientes fueron 62,33±8,66 mm; 93,31±9,89mm; 60,26±7,98 mm; 99,89±6,41 mm; 54,35±4,64 mm; 85,58±14,74 mm en sujetos con vértigo, respectivamente. Se encontraron los mismos valores para pacientes con demencia 58,82±8,34 mm; 86,74±13,22 mm; 58,93±8,89 mm; 97,93±6,07 mm; 50,66±4,92 mm; 84,96±14,93 mm , respectivamente, mientras que las mismas medidas fueron de 60,83±8,59 mm; 92,18±9,12 mm; 57,76±7,85 mm; 97,71±5,82 mm; 52,48±4,85 mm; 81,49±14,38 mm en pacientes con ataxia, respectivamente. Las edades se dividieron en siete grupos, cada uno en década. Se encontraron diferencias significativas en todos los parámetros según sexo y edad (p<0,05). La morfometría del cerebelo proporciona un conocimiento importante y útil en términos de comparación de anormalidades clínicas y los datos serán valiosos para la determinación de patologías para las disciplinas clínicas.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Cerebelo/diagnóstico por imagen , Ataxia , Imagen por Resonancia Magnética , Cerebelo/anatomía & histología , Factores Sexuales , Vértigo , Factores de Edad , Demencia , Trastornos Migrañosos

RESUMEN

Although many studies have been conducted on the effects of COVID-19 on individual lives, only a few focus on the changes in mental health and views of public institutions during the pandemic. This study aimed to investigate how mental health, i.e., life satisfaction, worries, and psychological distress, and views on public institutions' communication and activities have changed among Swedes during the COVID-19 pandemic, and whether this was moderated by age and sex. In April-May 2020 (survey 1) and in January-February 2021 (survey 2), 2554 adults and 1904 newly recruited adults, respectively, anonymously completed online surveys. We found that life satisfaction and psychological distress did not change from survey 1 to survey 2. However, the level of worries increased, and the positive views of the public institutions decreased. Moreover, worries and psychological distress increased more in young adults than older adults. Finally, the change in the views of the public institutions was not related to the change in worries. Our results highlight the COVID-19 long-term impacts on individual mental health and call for the need for future research concerning the consequences for the population, especially among young adults. The results also indicate that the views on activities of public authorities decreased over time, especially among men. Given that loss of this trust can have vastly negative effects, for instance, on the vaccine campaign, it is important to monitor this trend, to increase awareness among Swedish authorities. The results also stress for institutions to provide adequate support both during the COVID-19 pandemic and in a future crisis.

RESUMEN

Background: The novel coronavirus-19 (COVID-19) pandemic is a collective crisis that imposed an abrupt and unprecedented impact on college students, as universities were closed with little warning. Paired with the challenges associated with physical distancing (e.g. economic stress, job loss, food insecurity, housing challenges) and the simultaneous need to balance continued and new academic demands, impact will be wide-ranging. It is critical to determine the structure of the impact of this heterogeneous stressor (e.g. health concerns, pandemic worry, financial concerns) for prevention and intervention planning. Objective: Through an existing recruitment pipeline we were in a unique position to study the wide-ranging reach of this pandemic in a cohort of students for whom their university experiences were like no other cohort in history. Method: Data were collected from students who were in their third year of college during the onset of the pandemic; of the N = 1,899 in the cohort who were invited to participate in this COVID-related survey, 897 (47.2%) completed measures of impact between May and July of 2020. Results: A series of confirmatory and exploratory models were fit to examine the structure of the pandemic-related domains. Following estimation of a single-factor model, a correlated five factors model, as well as two second-order factor structures, the five correlated factors (exposure, worry, housing/food instability, social media, substance use) model was found to represent the data most appropriately, while producing an interpretable solution. Conclusions: These measurement model analyses set the stage for future research to examine how these correlated factors impact psychiatric, substance, and academic outcomes in this vulnerable population.

---

Antecedentes: La nueva pandemia de coronavirus-19 (COVID-19) es una crisis colectiva que impuso un impacto abrupto y sin precedentes en los estudiantes universitarios, ya que las universidades se cerraron con poco aviso. Junto con los desafíos asociados al distanciamiento físico (por ejemplo, el estrés económico, la pérdida de empleo, la inseguridad alimentaria, los problemas de vivienda) y la necesidad simultánea de equilibrar las demandas académicas continuas y nuevas, el impacto será de gran alcance. Es fundamental determinar la estructura del impacto de estos estresores heterogéneos (por ejemplo, las preocupaciones de salud, la preocupación por la pandemia, las preocupaciones financieras) para la planificación de la prevención y la intervención.Objetivo: A través de una línea de reclutamiento existente, nos encontramos en una posición única para estudiar el amplio alcance de esta pandemia en una cohorte de estudiantes para quienes sus experiencias universitarias fueron como ninguna otra cohorte en la historia.Método: Se recogieron datos de estudiantes que estaban en su tercer año de universidad durante el inicio de la pandemia; de los N = 1.899 de la cohorte que fueron invitados a participar en esta encuesta relacionada con la COVID, 897 (47,2%) completaron las medidas de impacto entre mayo y julio de 2020.Resultados: Se ajustaron una serie de modelos confirmatorios y exploratorios para examinar la estructura de los dominios relacionados con la pandemia. Tras la estimación de un modelo de un solo factor, un modelo correlacionado de cinco factores, así como dos estructuras factoriales de segundo orden, se encontró que el modelo de cinco factores correlacionados (exposición, preocupación, inestabilidad de la vivienda/alimentación, medios sociales, uso de sustancias) representaba los datos de forma más adecuada, a la vez que producía una solución interpretable.Conclusiones: Estos análisis del modelo de medición sientan las bases para futuras investigaciones que examinen cómo estos factores correlacionados impactan en los resultados psiquiátricos, de sustancias y académicos en esta población vulnerable.

RESUMEN

BACKGROUND: While survival in overall pediatric malignancy has improved during recent decades, brain/central nervous system (CNS) tumors has not demonstrated comparable survival advantage. Incidence and mortality data in this malignancy continue to illustrate race and sex differences; however, there are few data in the pediatric setting. This study sought to characterize brain/CNS tumors by socio-demographic and assess racial and sex variances in both cumulative incidence and mortality. METHODS: A retrospective cohort design with Surveillance, Epidemiology and End Results (SEER) 1973-2014 was used for the assessment of children aged < 1-19 years diagnosed with brain/CNS tumors. The age-adjusted incidence rates were used for temporal trends, percent change, and annual percent change. We utilized binomial regression model to determine the exposure effect of race and sex on cancer mortality, adjusting for potential confounders. RESULTS: Childhood brain/CNS tumor cumulative incidence (CmI) continues to rise in annual percent change, and mortality varied by race, sex, and year of diagnosis. The CmI was highest among whites, intermediate among blacks, and lowest among Asians, as well as lower in females relative to that in males. Compared to whites, blacks were 21% more likely to die from brain/CNS tumors [risk ratio (RR) 1.21, 95% confidence interval (C.I.) 1.13-1.28], while males were 4% more likely to die relative to females (RR 1.04, 95% C.I. 1.00-1.08). After controlling for age, sex, and tumor grade, racial disparities persisted, with 16% increased risk of dying among blacks relative to whites [adjusted risk ratio 1.16, (99% C.I.) 1.08-1.25, p < 0.001]. CONCLUSION: The cumulative incidence of brain/CNS malignancy is higher among whites relative to that in blacks; however, blacks experienced survival disadvantage even after adjustment for potential tumor prognostic and predisposing factors.

Asunto(s)

Neoplasias Encefálicas/etnología , Etnicidad/estadística & datos numéricos , Mortalidad/etnología , Adolescente , Negro o Afroamericano , Asiático , Neoplasias Encefálicas/mortalidad , Neoplasias del Sistema Nervioso Central/etnología , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Preescolar , Femenino , Disparidades en el Estado de Salud , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Programa de VERF , Distribución por Sexo , Población Blanca

RESUMEN

Work psychology has noted the importance of considering the temporal dimension of behavior in organizations. Given that society widely operates on a 24-hr schedule, it is important to know how circadian typologies are distributed in the general population. In this study, diurnal preference was analyzed among 4,175 Spanish participants (61.3% women), 12-59 years old, who completed the Composite Scale of Morningness (Smith, Reilly, & Midkiff, 1989). Several measurement models of the CSM were analyzed using exploratory structural equation modeling and confirmatory factor analysis. The bifactor model showed the best fit, with a general factor (morningness/eveningness) and three subfactors (morningness, morning affect, and time of retiring). The age and sex factorial invariance of the bifactor model were tenable at the latent variance-covariance level. Next, age and sex differences analysis indicated a progressive increase in morningness with age, but over 40 years old, men were more morningness oriented than women were. These results indicate that morningness/eveningness can be considered a multidimensional construct and that psychosocial factors must be considered when estimating the prevalence of morningness/eveningness in different populations or countries.

Asunto(s)

Ritmo Circadiano/fisiología , Desarrollo Humano/fisiología , Adolescente , Adulto , Factores de Edad , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , España , Adulto Joven

RESUMEN

In the present study, in vitro effects of synthetic vasotocin (VT), isotocin (4Ser, 8Ile- oxytocin; ITb) and the recently cloned IT gene paralog product (8Val-Isotocin, ITa) were studied on the expression of pituitary gonadotropin (GtH) subunit mRNA levels. In male pituitaries of early (preparatory phase) and late (prespawning phase) recrudescing catfish, Heteropneustes fossilis, VT (10 nM, 100 nM and 1000 nM) stimulated fshß expression dose-dependently. But in females, the dose-dependent effect was found only in the preparatory phase. In males, VT stimulated lhß expression only at higher doses. In females, VT produced a significant dose-dependent increase of the lhß expression only in the prespawning phase. VT stimulated the expression of gpα, dose-dependently in the preparatory phase in males and in the prespawning phase in females. The incubation of the pituitaries with ITb did not alter the fshß expression in either sex in both preparatory and prespawning phases. In males, ITb stimulated the expression of lhß and gpα only at the highest concentration (1000 nM) in both phases. In females, ITb stimulated both lhß and gpα expression only at 1000 nM in the preparatory phase and dose-dependently in the prespawning phase. The incubation of the pituitaries with ITa produced effects similar to ITb on the expression of fshß, lhß, and gpα. The results show that the basic peptide VT modulates both fshß and lhß expressions, which are influenced by the sex and reproductive stage. The neutral peptide ITA/ITb exerts an insignificant effect on the fshß expression regardless of sex or season. Both VT and ITa/ITb elicit a significant effect on the lhß expression in late recrudescent phase especially in females.

Asunto(s)

Bagres , Gonadotropinas Hipofisarias/genética , Hormonas Neurohipofisarias/farmacología , Reproducción/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Animales , Bagres/genética , Bagres/crecimiento & desarrollo , Bagres/metabolismo , Femenino , Hormona Folículo Estimulante de Subunidad beta/genética , Hormona Folículo Estimulante de Subunidad beta/metabolismo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Gonadotropinas Hipofisarias/metabolismo , Técnicas In Vitro , Hormona Luteinizante de Subunidad beta/genética , Hormona Luteinizante de Subunidad beta/metabolismo , Masculino , Oxitocina/análogos & derivados , Oxitocina/farmacología , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Reproducción/genética , Estaciones del Año , Caracteres Sexuales , Maduración Sexual/genética , Vasotocina/farmacología

RESUMEN

The monocyte-lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variation in MLR level in the general population is heritable and influenced by age, sex, and smoking. We identified gene variants in the ITGA4 gene associated with variation in MLR. The significant SNP-heritability indicates that more genetic variants are likely to be involved.

Asunto(s)

Estudio de Asociación del Genoma Completo , Linfocitos/citología , Monocitos/citología , Carácter Cuantitativo Heredable , Adulto , Índice de Masa Corporal , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Cadenas alfa de Integrinas/genética , Factores Reguladores del Interferón/genética , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Receptores del Ácido Lisofosfatídico/genética , Fumar/efectos adversos

RESUMEN

BACKGROUND: Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. METHODS: DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [(3)H]flunitrazepam binding to the mouse brain membranes. RESULTS: DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [(3)H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. CONCLUSION: Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status, which may underline observed sex differences in the relationship between DHEAS and various health outcomes.

Asunto(s)

Encéfalo/efectos de los fármacos , Sulfato de Deshidroepiandrosterona/farmacología , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Factores de Edad , Animales , Encéfalo/metabolismo , Sulfato de Deshidroepiandrosterona/administración & dosificación , Esquema de Medicación , Femenino , Flunitrazepam/metabolismo , Masculino , Ratones , Ratones Endogámicos CBA , Neuronas/metabolismo , Convulsiones/etiología , Factores Sexuales

RESUMEN

Prominent disturbances in the experience, expression, and emotion recognition in patients with schizophrenia have been relatively well documented over the last few years. Furthermore, sex differences in behavior and brain activity, associated with the processing of various emotions, have been reported in the general population and in schizophrenia patients. Others proposed that sex differences should be rather attributed to testosterone, which may play a role in the etiology of schizophrenia. Also, it had been suggested that estradiol may play a protective role in schizophrenia. Surprisingly, few studies investigating this pathology have focused on both brain substrates and gonadal steroid hormone levels, in emotional processing. In the present study, we investigated electrocortical responses related to emotional valence and arousal as well as gonadal steroid hormone levels in patients with schizophrenia. Event-Related Potentials (ERP) were recorded during exposition to emotional pictures in 18 patients with schizophrenia and in 24 control participants paired on intelligence, manual dominance and socioeconomic status. Given their previous sensitivity to emotional and attention processes, the P200, N200 and the P300 were selected for analysis. More precisely, emotional valence generally affects early components (N200), which reflect early process of selective attention, whereas emotional arousal and valence both influences the P300 component, which is related to memory context updating, and stimulus categorization. Results showed that, in the control group, the amplitude of the N200 was significantly more lateralized over the right hemisphere, while there was no such lateralization in patients with schizophrenia. In patients with schizophrenia, significantly smaller anterior P300 amplitude was observed to the unpleasant, compared to the pleasant. That anterior P300 reduction was also correlated with negative symptoms. The N200 and P300 amplitudes were positively correlated with the estradiol level in all conditions, revealing that the N200 and the P300 were reduced, when estradiol level was higher. Conversely, only the P300 amplitude showed positive correlation with the testosterone level.