Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools.

Technical innovation in neuroscience introduced powerful tools for measuring and manipulating neuronal activity via optical, chemogenetic, and calcium-imaging tools. These tools were initially tested primarily in male animals but are now increasingly being used in females as well. In this review, we consider how these tools may work differently in males and females. For example, we review sex differences in the metabolism of chemogenetic ligands and their downstream signaling effects. Optical tools more directly alter depolarization or hyperpolarization of neurons, but biological sex and gonadal hormones modulate synaptic inputs and intrinsic excitability. We review studies demonstrating that optogenetic manipulations are sometimes consistent across the rodent estrous cycle but within certain circuits; manipulations can vary across the ovarian cycle. Finally, calcium-imaging methods utilize genetically encoded calcium indicators to measure neuronal activity. Testosterone and estradiol can directly modulate calcium influx, and we consider these implications for interpreting the results of calcium-imaging studies. Together, our findings suggest that these neuroscientific tools may sometimes work differently in males and females and that users should be aware of these differences when applying these methods.

Prevalence of the H5N8 influenza virus in birds: Systematic review with meta-analysis.

INTRODUCTION: Avian influenza viruses are members of the Orthomyxoviridae family, considered highly pathogenic (HPAI). They result from genetic variations from their low virulence predecessors. HPAI is a global problem. Large outbreaks of HAPI have significant health and economic impacts. OBJECTIVE: The objective of this study was to assess the prevalence of the H5N8 Influenza virus in birds, as well as to assess its variability according to the countries and years. METHODS: A systematic review of the literature was carried out in six databases (Web of Sciences, Scopus, PubMed, SciELO, Lilacs and Google Scholar) to evaluate the proportion of birds infected with the H5N8 Influenza virus, by molecular and immunological techniques. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence, 95% confidence intervals (95%CI). A 2-tailed 5% alpha level was used for hypothesis testing. Measures of heterogeneity were estimated and reported, including the Cochrane Q statistic, the I2 index, and the tau-squared test. In addition, bird species performed subgroup analyzes. RESULTS: 152 data groups were analyzed, a combined prevalence of 1.6% (95% CI 1.3-1.9%) was found for molecular studies, and the ELISA study yielded a seroprevalence of 66.7%; those results of molecular detection varied by year, from 0.2% in 2014 to 52.6% in 2020 and 96.9% in 2015. CONCLUSION: The combined prevalence was substantial because large outbreaks have caused severe economic repercussions. In addition, it is considered a serious concern for public health due to its possible zoonotic activity.

A Cre-driver rat model for anatomical and functional analysis of glucagon (Gcg)-expressing cells in the brain and periphery.

OBJECTIVE: The glucagon gene (Gcg) encodes preproglucagon, which is cleaved to form glucagon-like peptide 1 (GLP1) and other mature signaling molecules implicated in metabolic functions. To date there are no transgenic rat models available for precise manipulation of GLP1-expressing cells in the brain and periphery. METHODS: To visualize and manipulate Gcg-expressing cells in rats, CRISPR/Cas9 was used to express iCre under control of the Gcg promoter. Gcg-Cre rats were bred with tdTomato reporter rats to tag Gcg-expressing cells. Cre-dependent AAVs and RNAscope in situ hybridization were used to evaluate the specificity of iCre expression by GLP1 neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt), and by intestinal and pancreatic secretory cells. Food intake was assessed in heterozygous (Het) Gcg-Cre rats after chemogenetic stimulation of cNTS GLP1 neurons expressing an excitatory DREADD. RESULTS: While genotype has minimal effect on body weight or composition in chow-fed Gcg-Cre rats, homozygous (Homo) rats have lower plasma glucose levels. In neonatal and adult Gcg-Cre/tdTom rats, reporter-labeled cells are present in the cNTS and IRt, and in additional brain regions (e.g., basolateral amygdala, piriform cortex) that lack detectable Gcg mRNA in adults but display transient developmental or persistently low Gcg expression. Compared to wildtype (WT) rats, hindbrain Gcg mRNA and GLP1 protein in brain and plasma are markedly reduced in Homo Gcg-Cre rats. Chemogenetic stimulation of cNTS GLP1 neurons reduced overnight chow intake in males but not females, the effect in males was blocked by antagonism of central GLP1 receptors, and hypophagia was enhanced when combined with a subthreshold dose of cholecystokinin-8 to stimulate gastrointestinal vagal afferents. CONCLUSIONS: Gcg-Cre rats are a novel and valuable experimental tool for analyzing the development, anatomy, and function of Gcg-expressing cells in the brain and periphery. In addition, Homo Gcg-Cre rats are a unique model for assessing the role of Gcg-encoded proteins in glucose homeostasis and energy metabolism.

Repetitive Mild Traumatic Brain Injury in an Awake, Unanesthetized Mouse Model of Perinatal Nicotine Exposure Produces Transient Novelty-Seeking and Depression-Like Behaviors.

Attention deficit hyperactivity disorder (ADHD) can be a risk factor for repetitive mild traumatic brain injury (mTBI) or concussions such as those that can occur in contact sports. Individuals with ADHD also appear to have a higher risk of poor neurocognitive outcomes after repetitive mTBI. Findings from clinical studies examining the interactions between ADHD and repetitive mTBI vary, likely because of variabilities in experimental design and outcome measures. We used a mouse model of perinatal nicotine exposure (PNE), which displays behavioral, neuroanatomical, and neurotransmitter features consistent with ADHD and subjected the mice to repetitive mTBI. We used a closed head model of mTBI in awake, unanesthetized mice to mimic concussions in humans. The mTBI was repeated three times daily for seven days. The mice in the PNE-mTBI group took longer to regain consciousness after the mTBI and showed transient novelty-seeking and depression-like behaviors. Before the repetitive mTBI, the mice in the PNE group showed attention deficit, which persisted after the mTBI. The mice in the control (non-PNE) group showed a transient attention deficit after the repetitive mTBI but not any of the other behavioral changes seen in the PNE-mTBI group. These findings from an unanesthetized mouse model with a pre-existing condition show that ADHD and repetitive mTBI together contribute to transient novelty-seeking and depression-like behavior supporting the notion that untreated ADHD may be a risk factor for poor neurocognitive outcomes after concussions.

Feasibility of using death certificates for studying place of death in Latin America.

OBJECTIVE: This paper assesses the availability and quality of death certificate data in Latin America and the feasibility of using these data to study place of death and associated factors. METHODS: In this comparative study, we collected examples of current official death certificates and digital data files containing information about all deaths that occurred during 1 year in 19 Latin American countries. Data were collected from June 2019 to May 2020. The records for place of death and associated variables were studied. The criteria for data quality were completeness, number of ill-defined causes of death and timeliness. RESULTS: All 19 countries provided copies of current official death certificates and 18 of these registered the place of death. Distinguishing among hospital or other health care institution, home and other was possible for all countries. Digital data files with death certificate data were available from 12 countries and 1 region. Three countries had data considered to be of high quality and seven had data considered to be of medium quality. Categories for place of death and most of the predetermined factors possibly associated with place of death were included in the data files. CONCLUSIONS: The quality of data sets was rated medium to high in 10 countries. Hence, death certificate data make it feasible to conduct an international comparative study on place of death and the associated factors in Latin America.

Feasibility of using death certificates for studying place of death in Latin America

[ABSTRACT]. Objective. This paper assesses the availability and quality of death certificate data in Latin America and the feasibility of using these data to study place of death and associated factors. Methods. In this comparative study, we collected examples of current official death certificates and digital data files containing information about all deaths that occurred during 1 year in 19 Latin American countries. Data were collected from June 2019 to May 2020. The records for place of death and associated variables were studied. The criteria for data quality were completeness, number of ill-defined causes of death and timeliness. Results. All 19 countries provided copies of current official death certificates and 18 of these registered the place of death. Distinguishing among hospital or other health care institution, home and other was possible for all countries. Digital data files with death certificate data were available from 12 countries and 1 region. Three countries had data considered to be of high quality and seven had data considered to be of medium quality. Categories for place of death and most of the predetermined factors possibly associated with place of death were included in the data files. Conclusions. The quality of data sets was rated medium to high in 10 countries. Hence, death certificate data make it feasible to conduct an international comparative study on place of death and the associated factors in Latin America.

[RESUMEN]. Objetivo. En este artículo se evalúa la disponibilidad y la calidad de los datos del certificado de defunción en América Latina y la factibilidad de emplear estos datos para estudiar el lugar de defunción y factores asociados. Métodos. En este estudio comparativo, se recogieron ejemplos de certificados oficiales de defunción actuales y archivos digitales de datos que contenían información acerca de todas las defunciones que ocurrieron durante un año en 19 países latinoamericanos. Se recopilaron datos desde junio del 2019 hasta mayo del 2020. Se estudiaron los registros del lugar de la muerte y las variables asociadas. Los criterios para determinar la calidad de los datos fueron la exhaustividad, el número de causas de muerte mal definidas y la presentación oportuna de la información. Resultados. Los 19 países proporcionaron copias de los certificados oficiales de defunción actuales; en 18 de estos se registraba el lugar de la muerte. En todos los países fue posible distinguir entre hospital u otra institución de atención de salud, el hogar y otros. Se obtuvieron los archivos de datos digitales con los datos del certificado de defunción de 12 países y una región. Tres países tenían datos considerados de buena calidad y siete tenían datos considerados de calidad media. En los archivos de datos se incluyeron categorías para lugar de defunción y la mayoría de los factores predeterminados posiblemente asociados con el lugar de defunción. Conclusiones. La calidad de los conjuntos de datos se calificó de media a buena en 10 países. En consecuencia, es factible realizar un estudio internacional comparativo sobre el lugar de defunción y los factores asociados en América Latina con los datos del certificado de defunción.

[RESUMO]. Objetivo. Este estudo avalia a disponibilidade e a qualidade dos dados das declarações de óbito na América Latina e a viabilidade de usar esses dados para estudar o local do óbito e fatores associados. Métodos. Neste estudo comparativo, coletamos exemplos de declarações de óbito oficiais atuais e arquivos de dados digitais contendo informações sobre todos os óbitos que ocorreram durante 1 ano em 19 países latinoamericanos. Os dados foram coletados no período de junho de 2019 a maio de 2020. Foram estudados os registros do local do óbito e variáveis associadas. Os critérios de qualidade dos dados foram preenchimento completo, número de causas mal definidas de morte e oportunidade. Resultados. Todos os 19 países forneceram cópias das declarações de óbito oficiais atuais, e 18 deles registraram o local do óbito . Foi possível distinguir em todos os países entre hospital ou outra instituição de saúde, lar ou outro local. Arquivos de dados digitais com os dados das declarações de óbito foram disponibilizados por 12 países e 1 região. Três países tiveram dados considerados de alta qualidade, e sete tiveram dados considerados de qualidade média. As categorias de local do óbito e a maioria dos fatores predeterminados possivelmente associados ao local do óbito foram incluídos nos arquivos de dados. Conclusões. A qualidade dos conjuntos de dados foi classificada como média a alta em 10 países. Portanto, os dados de declarações de óbito possibilitam a realização de um estudo comparativo internacional sobre local do óbito e fatores associados na América Latina.

Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) increases the risk for concussion or mild traumatic brain injury (mTBI). At the same time, recommendations for the management of ADHD include participation in sports and other organized physical activities, including those that carry an increased risk of mTBI. Very little work has been done to determine the extent to which untreated ADHD adversely impacts behavioral outcomes of repeated mild concussions. Here, we used a perinatal nicotine exposure (PNE) mouse model of ADHD combined with a closed-head, repetitive mTBI model. The PNE mouse model carries significant construct, face, and predictive validity as a preclinical model of ADHD. Two-month-old PNE and control mice were subjected to closed-head repetitive mTBI or sham procedure once daily for 5 days. Object-based attention, novel object recognition memory, spatial working memory, and depression-like behavior were analyzed 1 day and 2 weeks following repeated mTBI. Consistent with our previous reports, mice in the PNE group showed significant deficits in object-based attention and working memory prior to mTBI. These deficits persisted following the repeated mTBI. Repeated mTBI produced a transient attention deficit in the control group but did not exacerbate the attention deficit that is characteristic of the PNE group. Although neither PNE nor repetitive mTBI alone influenced immobility in the tail suspension test, when PNE mice were subjected to mTBI, there was a transient increase in this measurement suggesting a synergistic effect of ADHD and mTBI on depression-like behavior. Thus, our data using the PNE mouse model suggest that ADHD may be a risk factor for transient depression following repeated mTBI and that repeated mTBI may be a risk factor for transient attention deficit.

Feasibility of using death certificates for studying place of death in Latin America

Objective: this paper assesses the availability and quality of death certificate data in Latin America and the feasibility of using these data to study place of death and associated factors. Methods: in this comparative study, we collected examples of current official death certificates and digital data files containing information about all deaths that occurred during 1 year in 19 Latin American countries. Data were collected from June 2019 to May 2020. The records for place of death and associated variables were studied. The criteria for data quality were completeness, number of ill-defined causes of death and timeliness. Results: all 19 countries provided copies of current official death certificates and 18 of these registered the place of death. Distinguishing among hospital or other health care institution, home and other was possible for all countries. Digital data files with death certificate data were available from 12 countries and 1 region. Three countries had data considered to be of high quality and seven had data considered to be of medium quality. Categories for place of death and most of the predetermined factors possibly associated with place of death were included in the data files. Conclusions: the quality of data sets was rated medium to high in 10 countries. Hence, death certificate data make it feasible to conduct an international comparative study on place of death and the associated factors in Latin America.

Relación entre cifras de tensión arterial e indicadores de sobrepeso en población de adolescentes escolarizados de Manizales, Colombia, 2011 / Relationship between blood pressure, body mass index in school population of Manizales, Colombia, 2011

Antecedentes: La obesidad se relaciona con el desarrollo de hipertensión arterial en el adulto, se pretende estudiar la presencia de indicadores de riesgo de sobrepeso y su relación con cifras tensionales altas en una población de adolescentes escolarizados de Manizales (Colombia). Materiales y métodos: Participaron en el estudio 923 adolescentes. A estos se les tomaron las medidas antropomértricas, y tensión arterial. Resultados: 51,1% de sexo femenino, entre 10 y 18 años de edad, con promedio de 14,25 sños. El 82,4% de los adolescentes presentaron un índice de masa corporal normal, promedio de índice cintura cadera de 0,85, promedio de perímetro abdominal de 74,99 cms, y de índice de masa corporal de 20,74 en niñas y 74,87, 0,87 y 20,29 en jóvenes. El promedio de presión arterial sistólica fue de 102.07 mmHg para mujeres y 103,62 mmHg para los hombres, en cuanto a la presión diastólica el promedio para mujeres fue de 63,45 mmHg y en los hombres fue de 64,07 mmHg. Tanto los análisis univariados como multivariados mostraron una relación significativa de ambas presiones, tanto para mujeres como paras hombres en todos los casos con el índice de masa corporal, los análisis multivariados mostraron dependencia de ambas medidas de presión con perímetro abdominal para hombres, en mujeres solo el análisis univariado mostró relación con la presión arterial diastólica, el índice cintura caderano mostró relación con nada en ningún caso. Conclusión: El indicador de sobrepeso más apropiado para medir riesgo de hipertensión en adolescentes es el índice de masa corporal...

Tumor de células gigantes de hueso: serie de casos durante 64 años en un único centro / Giant cell tumor of bone: a 64 years single center experience

Introducción: El tumor de células gigantes de hueso es una lesión localmente agresiva que tien-de a la recurrencia local y ocasionalmente presenta metástasis a distancia. Objetivo: describir la presentación clínica e histológica y la frecuencia relativa del tumor de células gigantes de hueso en un único centro, Medellín-Colombia. Materiales y métodos: estudio descriptivo; se revisaron todos los casos diagnosticados como tumor de células gigantes de hueso entre 1944 y 2008 en el Departamento de Patología de la Universidad de Antioquia, y para cada uno se revisaron las prin-cipales características clínicas e histológicas. Resultados: entre 1944 y 2008 se diagnosticaron 2.185 tumores óseos; de éstos, 302 tenían diagnóstico de tumor de células gigantes del hueso y se confirmó el diagnóstico en 117, correspondiente al 5,3% de todos los tumores óseos. La rela-ción mujer: hombre fue de 1,1:1. Las localizaciones más frecuentes fueron fémur distal (19,7%), tibia proximal (25,6%), manos y pies (11,1%), radio distal (9,4%) y húmero proximal (8,5%). Las características histológicas atípicas que se observaron fueron áreas fusocelulares, invasión de tejidos blandos, necrosis, hemorragia, áreas de quiste óseo aneurismático secundario, áreas de células mononucleadas con escasas células gigantes y formación de osteoide dentro del tumor...

Introduction: Giant cell tumors of bone are locally aggressive lesions that tend to recur locally and that rarely metastasize. Objective: to describe clinical and histological features, and relative frequency of giant cell tumors of bone in a single center, in the city of Medellín-Colombia. Materials and methods: a cross-sectional study was conducted. All the tumors diagnosed as giant cell tumor of bone between 1944 and 2008 in the Department of Pathology of Universidad de Antioquia were reviewed, and for each patient, important clinical and histological features were assessed. Results: between the years 1944 and 2008, 2,185 bone tumors were diagnosed; of these, 302 were diagnosed as giant cell tumor of bone, but in this study the diagnosis was confirmed only in 117 cases; 5.3% of all bone tumors. The female: male ratio was 1.1:1. The tumors were most requently found in the distal femur (19.7%), proximal tibia (25.6%), hands and feet (11.1%), distal radio (9.4%), and proximal humerus (8.5%). Atypical features observed in the tumors included spindle cell areas, soft tissue invasion, necrosis, hemorrhage, aneurysmal bone cyst-like changes, and osteoid formation...