Demographic history and genetic structure in pre-Hispanic Central Mexico.

Aridoamerica and Mesoamerica are two distinct cultural areas in northern and central Mexico, respectively, that hosted numerous pre-Hispanic civilizations between 2500 BCE and 1521 CE. The division between these regions shifted southward because of severe droughts ~1100 years ago, which allegedly drove a population replacement in central Mexico by Aridoamerican peoples. In this study, we present shotgun genome-wide data from 12 individuals and 27 mitochondrial genomes from eight pre-Hispanic archaeological sites across Mexico, including two at the shifting border of Aridoamerica and Mesoamerica. We find population continuity that spans the climate change episode and a broad preservation of the genetic structure across present-day Mexico for the past 2300 years. Lastly, we identify a contribution to pre-Hispanic populations of northern and central Mexico from two ancient unsampled "ghost" populations.

Variability in sub-threshold signaling linked to Alzheimer's disease emerges with age and amyloid plaque deposition in mouse ventral CA1 pyramidal neurons.

The hippocampus is vulnerable to deterioration in Alzheimer's disease (AD). It is, however, a heterogeneous structure, which may contribute to the differential volumetric changes along its septotemporal axis during AD progression. Here, we investigated amyloid plaque deposition along the dorsoventral axis in two strains of transgenic AD (ADTg) mouse models. We also used patch-clamp physiology in these mice to probe for functional consequences of AD pathogenesis in ventral hippocampus, which we found bears significantly higher plaque burden in the aged ADTg group compared to corresponding dorsal regions. Despite dorsoventral differences in amyloid load, ventral CA1 pyramidal neurons of aged ADTg mice exhibited subthreshold physiological changes similar to those previously reported in dorsal neurons, indicative of an HCN channelopathy, but lacked exacerbated suprathreshold accommodation. Additionally, HCN channel function could be rescued by pharmacological manipulation of the endoplasmic reticulum. These observations suggest that an AD-linked HCN channelopathy emerges in both dorsal and ventral CA1 pyramidal neurons, but that the former encounter an additional integrative obstacle in the form of reduced intrinsic excitability.

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others' lifespans outlast their "mindspans."

Preoperative Differentiation of Benign and Malignant Non-epithelial Ovarian Tumors: Clinical Features and Tumor Markers.

OBJECTIVE: To evaluate the role of clinical features and preoperative measurement of cancer antigen 125 (CA125), human epididymis protein (HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. METHODS: One hundred and nineteen consecutive women with germ cell, sex cord-stromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. RESULTS: Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, among malignant, four were immature teratomas. The most common tumors in the sex cord-stromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign and malignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. CONCLUSION: Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant cases were diagnosed at initial stages with good prognosis. The measurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

OBJETIVO: Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. MéTODOS: Cento e dezenove mulheres consecutivas com tumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. RESULTADOS: Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estroma malignos foram tratadas com cirurgia preservadora de fertilidade. Cinco (71,4%) mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. CONCLUSãO: Os tumores de ovário não epiteliais foram benignos na maioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico pré-operatório desses tumores.

Impacto del COVID-19 en la educación de los estudiantes de medicina del Perú / Impact Of COVID-19 On The Education Of Medical Students In Peru

La pandemia por el coronavirus del Síndrome Respiratorio Agudo Grave 2 (SARS-CoV-2) que causa la enfermedad Coronavirus 2019 (COVID-19), es una enfermedad altamente contagiosa que representa una emergencia a nivel mundial. Al 22 de mayo del 2020 se cuenta con 4 993 470 casos confirmados y 327738 muertes entre 188 países/regiones, al mismo tiempo en Perú ya existen 111 698 casos positivos y 3244 fallecidos; datos que seguirán extendiéndose y poniendo en peligro la vida de miles de personas, afectando a estados, municipios e instituciones públicas y privadas; en tal sentido, se están tomando medidas más estrictas en el manejo de la cuarentena, aislamiento y distanciamiento social obligatorio, lo que repercute directamente en todas las actividades que involucren las reuniones presenciales.

The pandemic caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) caused by the Coronavirus disease 2019 (COVID-19) is a highly contagious disease that represents an emergency worldwide. On May 22, 2020 we counted 4,993,470 confirmed cases and 327,738 deaths among 188 countries/regions, at the same time there already existed 111,698 positive cases and 3,244 deaths in Peru already existed; data that will continue to expand and that places thousands of lives in danger, affecting states, municipalities and public and private institutions. In that regard, stricter measures are being taken with the obligatory quarantine, isolation and social distancing management, which directly affects all activities that involve in person gatherings.

Retrospective Review of Clinical and Chest X-Ray Findings in Children Admitted to a Community Hospital for Respiratory Syncytial Virus Infection.

INTRODUCTION: We performed a retrospective study to evaluate demographics, clinical course, outcome, and radiological findings of children with respiratory syncytial virus (RSV) infection. METHODS: Four hundred patients admitted between October 2013 and May 2016 were enrolled. Clinical and radiographic trends were evaluated for association with severity of RSV presentation. Severity was defined as hospitalization >2 days, pediatric intensive care unit admission, or need for mechanical ventilation. RESULTS: Common clinical findings included fever (78.5%), coughing (97%), rhinorrhea/congestion (93%), and hypoxia (44.8%). Hypoxia was seen in 64.7% of the severe group compared with 32.0% in the nonsevere group ( P < .001). Airspace opacification was seen in 49.2% of chest X-rays of the severe group compared with 26.4% in the nonsevere group ( P < .001). CONCLUSION: Higher incidence of hypoxia or airspace opacification on chest X-ray may be predictors of poorer outcomes for patients with RSV infection.

Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer's disease.

Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are misregulated in several neurological disorders, causing both gain- and loss-of-function channelopathies in neurons. Using several transgenic mouse models of Alzheimer's disease (AD), we find that sub-threshold voltage signals strongly influenced by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels progressively deteriorate over chronological aging in hippocampal CA1 pyramidal neurons. The degraded signaling via HCN channels in the transgenic mice is accompanied by an age-related global loss of their non-uniform dendritic expression. Both the aberrant signaling via HCN channels and their mislocalization could be restored using a variety of pharmacological agents that target the endoplasmic reticulum (ER). Our rescue of the HCN channelopathy helps provide molecular details into the favorable outcomes of ER-targeting drugs on the pathogenesis and synaptic/cognitive deficits in AD mouse models, and implies that they might have beneficial effects on neurological disorders linked to HCN channelopathies.

Age-dependent contribution of P/Q- and R-type Ca2+ channels to neuromuscular transmission in lethargic mice.

ß-Subunits of voltage-gated calcium channels (VGCCs) regulate assembly and membrane localization of the pore-forming α1-subunit and strongly influence channel function. ß4-Subunits normally coassociate with α1A-subunits which comprise P/Q-type (Cav2.1) VGCCs. These control acetylcholine (ACh) release at adult mammalian neuromuscular junctions (NMJs). The naturally occurring lethargic (lh) mutation of the ß4-subunit in mice causes loss of the α1-binding site, possibly affecting P/Q-type channel expression or function, and thereby ACh release. End-plate potentials and miniature end-plate potentials were recorded at hemidiaphragm NMJs of 5-7-week and 3-5-month-old lh and wild-type (wt) mice. Sensitivity to antagonists of P/Q- [ω-agatoxin IVA (ω-Aga-IVA)], L- (nimodipine), N- (ω-conotoxin GVIA), and R-type [C192H274N52O60S7 (SNX-482)] VGCCs was compared in juvenile and adult lh and wt mice. Quantal content (m) of adult, but not juvenile, lh mice was reduced compared to wt. ω-Aga-IVA (~60%) and SNX-482 (~ 45%) significantly reduced m in adult lh mice. Only Aga-IVA affected wt adults. In juvenile lh mice, ω-Aga-IVA and SNX-482 decreased m by >75% and ~20%, respectively. Neither ω-conotoxin GVIA nor nimodipine affected ACh release in any group. Immunolabeling revealed α1E and α1A, ß1, and ß3 staining at adult lh, but not wt NMJs. Therefore, in lh mice, when the ß-subunit that normally coassociates with α1A to form P/Q channels is missing, P/Q-type channels partner with other ß-subunits. However, overall participation of P/Q-type channels is reduced and compensated for by R-type channels. R-type VGCC participation is age-dependent, but is less effective than P/Q-type at sustaining NMJ function.

Evidence for Alzheimer's disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons.

Alzheimer's disease (AD) is associated with alterations in the distribution, number, and size of inputs to hippocampal neurons. Some of these changes are thought to be neurodegenerative, whereas others are conceptualized as compensatory, plasticity-like responses, wherein the remaining inputs reactively innervate vulnerable dendritic regions. Here, we provide evidence that the axospinous synapses of human AD cases and mice harboring AD-linked genetic mutations (the 5XFAD line) exhibit both, in the form of synapse loss and compensatory changes in the synapses that remain. Using array tomography, quantitative conventional electron microscopy, immunogold electron microscopy for AMPARs, and whole-cell patch-clamp physiology, we find that hippocampal CA1 pyramidal neurons in transgenic mice are host to an age-related synapse loss in their distal dendrites, and that the remaining synapses express more AMPA-type glutamate receptors. Moreover, the number of axonal boutons that synapse with multiple spines is significantly reduced in the transgenic mice. Through serial section electron microscopic analyses of human hippocampal tissue, we further show that putative compensatory changes in synapse strength are also detectable in axospinous synapses of proximal and distal dendrites in human AD cases, and that their multiple synapse boutons may be more powerful than those in non-cognitively impaired human cases. Such findings are consistent with the notion that the pathophysiology of AD is a multivariate product of both neurodegenerative and neuroplastic processes, which may produce adaptive and/or maladaptive responses in hippocampal synaptic strength and plasticity.

Escola de Música de Manguinhos / Manguinhos School of Music

O Projeto Escola de Música de Manguinhos (EMM) teve início em 2008 e, em 2011, entrou em fase de consolidação e expansão. Seu objetivo principal é proporcionar ensino de música a crianças, jovens e adultos da Comunidade de Manguinhos, comunidade esta de baixa renda, objetivando contribuir para a formação e/ou profissionalização desses alunos, bem como para a transformação da realidade social da comunidade. O projeto resulta de uma parceria com a Rede CCAP, OSCIP sediada em Manguinhos, e conta com apoio da Fundação Oswaldo Cruz e da empresa italiana CESVI. A EMM vincula-se à Escola de Música da UFRJ, através do Programa de Pós-Graduação em Música e do Departamento de Musicologia e Educação Musical (Centro de Estudos de Musicologia e Educação Musical), no qual está lotada a coordenadora. Os professores são ALUNOS DE GRADUAÇÃO/UFRJ e de PÓS-GRADUAÇÂO, alguns deles recém-formados (apoios FIOCRUZ e PIBEX/UFRJ). Os fundamentos teórico-metodológicos valorizam a permeabilidade entre metodologias formais, não formais e informais de ensino de música, com opção pelas visões articuladas da pedagogia dialética, da pedagogia crítico-social dos conteúdos e da pedagogia pós-moderna. A EMM propicia laboratório e campo de pesquisa sobre métodos de ensino de música e é acompanhado e avaliado por projeto de pesquisa, gerando comunicações em congressos nacionais e internacionais e publicações diversas...

Geração de modelos de regionalização de vazões máximas, médias de longo período e mínimas de sete dias para a bacia do rio do Carmo, Minas Gerais / Models generation of regionalization of maximum, medium and minimum of seven days flow rates for the Carmo river basin, Minas Gerais

O fato de ser limitada a disponibilidade hídrica de uma bacia hidrográfica, aliado ao crescente aumento da demanda motivado pelos mais variados usos e impulsionado pelo desenvolvimento econômico, exige a adoção de critérios de gestão capazes de minimizar os inevitáveis conflitos pelo uso da água. Para que a gestão seja adequada, requer-se o conhecimento dos diferentes segmentos do ciclo hidrológico, notadamente da precipitação e da vazão. Com isso, e considerando-se a importância de se verem atendidas as regiões com ausência ou escassez de dados fluviométricos, desenvolveu-se o presente estudo de construção de modelos matemáticos de regionalização de vazões na bacia do rio do Carmo. Para isso, foram construídas as séries de chuvas totais anuais, totais do semestre mais chuvoso e máximas diárias, e as séries de vazões máximas, médias e mínimas. As séries de chuvas no ponto foram convertidas em chuvas na área com o uso do método de Thiessen. Com base nas séries anuais das vazões máximas, médias e mínimas, ajustaram-se modelos de probabilidade que permitiram a extrapolação dos dados históricos. Ainda, para pesquisar a influência do relevo sobre as variáveis hidrológicas foram feitas as quantificações de diferentes parâmetros que caracterizam a bacia. Deste modo, ao final foram construídos os modelos de regionalização das vazões.