The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence.

Rejuvenation of an old organism was achieved in heterochronic parabiosis experiments, implicating different soluble factors in this effect. Extracellular vesicles (EVs) are the secretory effectors of many cells, including cardiosphere-derived cells (CDCs) with demonstrated anti-senescent effect. 1. To determine the role of EVs (versus other blood fractions) on the rejuvenating effect of the young blood. 2. To evaluate the anti-aging properties of therapeutically administered EVs secreted by young-CDCs in an old organism. Neonatal blood fractioned in 4 components (whole blood, serum, EV-depleted serum and purified EVs) was used to treat old human cardiac stromal cells (CSPCs). CDCs were generated from neonatal rat hearts and the secreted CDC-EVs were purified. CDC-EVs were then tested in naturally-aged rats, using monthly injections over 4-months period. For validation in human samples, pediatric CDC-EVs were tested in aged human CSPCs and progeric fibroblasts. While the purified EVs reproduced the rejuvenating effects of the whole blood, CSPCs treated with EV-depleted serum exhibited the highest degree of senescence. Treatment with young CDC-EVs induce structural and functional improvements in the heart, lungs, skeletal muscle, and kidneys of old rats, while favorably modulating glucose metabolism and anti-senescence pathways. Lifespan was prolonged. EVs secreted by young CDCs exert broad-ranging anti-aging effects in aged rodents and in cellular models of human senescence. Our work not only identifies CDC-EVs as possible therapeutic candidates for a wide range of age-related pathologies, but also raises the question of whether EVs function as endogenous modulators of senescence.

Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury.

Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial-grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation.

Assessing fetal human neural stem cells tumorigenicity potential in athymic rats with penetrating traumatic brain injury (pTBI).

Traumatic brain injuries (TBI) often produce disability in survivors due to unresolved inflammation and progressive neurodegeneration. The central nervous system in mammals is incapable of self-repair. Two decades of preclinical studies and clinical trials have provided insights into TBI pathophysiology that could be utilized to develop clinically relevant therapy. Our laboratory recently reported efficacy of clinical trial grade fetal human neural stem cells (hNSCs) in immunosuppressed rats with penetrating traumatic brain injury (pTBI). Next, in compliance with the United States Food and Drug Administration (USFDA) guidance, this study explores safety by assessing the tumorigenicity potential of intracranial hNSC transplants in athymic rats with pTBI. First, the maximum tolerated dose (MTD) was determined. Then, forty athymic pTBI rats were randomized to either: Group A. pTBI + vehicle or Group B. pTBI + hNSCs at MTD one week after injury with 6-months survival, sufficient time to uncover transplant associated tumorigenicity. A board-certified Pathologist examined hematoxylin-eosin (H&E), Ki67 immunostained brain and spinal cord, serial sections along with several abnormal peripheral masses for evidence of lesion, transplant, and oncogenesis. There was no evidence of transplant derived tumors or oncogenic tissue necrosis. Consistent with athymic literature, the lesion remained unchanged even after robust hNSC engraftment. This safety study supports the conclusion that hNSCs are safe for transplantation in pTBI. The differences in lesion expansion between immunosuppressed and athymic rats in the presence of hNSCs suggests an unexpected role for thymus derived cells in resolution of trauma induced inflammation.

Factores asociados a la homofobia en estudiantes de Medicina de once universidades peruanas / Factors associated with homophobia in medical students from eleven Peruvian universities

RESUMEN Introducción: Las consecuencias de la homofobia pueden afectar a la integridad y la salud mental y física de los individuos homosexuales en la sociedad. En Perú hay escasos estudios que hayan evaluado la homofobia en la población médico-estudiantil. Objetivo: Determinar los factores sociales, educativos y culturales asociados con la homofobia entre estudiantes de Medicina peruanos. Métodos: Se realizó un estudio de tipo transversal analítico en 12 sedes de Medicina humana peruanas. Se definió homofobia según un test validado, que se asoció con otras variables. Se obtuvieron estadísticos de asociación. Resultados: Las 4 universidades de Lima obtuvieron menores porcentajes de alumnos homofóbicos (15-20%) que las universidades del interior del país (22-62%). Al realizar el análisis multivariable, disminuyeron la frecuencia de homofobia: ser mujer (RPa = 0,74; IC95%, 0,610,92; p = 0,005), estudiar en una universidad de Lima (RPa = 0,57; IC95%, 0,43-0,75; p < 0,001), profesar la religión católica (RPa = 0,53; IC95%, 0,37-0,76; p < 0,001), conocer a un homosexual (RPa = 0,73; IC95%, 0,60-0,90; p = 0,003) y haber atendido a un paciente homosexual (RPa = 0,76; IC95%, 0,59-0,98; p = 0,036); en cambio, ser machista aumentó la frecuencia de homofobia (RPa = 1,37; IC95%, 1,09-1,72; p = 0,007), ajustado por 4 variables. Conclusiones: La homofobia fue menos frecuente entre las mujeres, los que estudiaban en la capital, los que profesan el catolicismo y los que conocen/han atendido a un homosexual; por el contrario, los machistas fueron más homofóbicos.

ABSTRACT Background: The consequences of homophobia can affect the integrity, mental and physical health of homosexual individuals in society. There are few studies in Peru that have evaluated homophobia in the medical student population. Objective: To establish the social, educational and cultural factors associated with homophobia among Peruvian medical students. Methods: A cross-sectional analytical study was conducted in 12 medicine schools in Peru. Homophobia was defined according to a validated test, which was associated with other variables. Statistical associations were identified. Results: The lowest percentages of homophobic students (15-20%) were found in the four universities in Lima, while universities in the interior of the country had the highest percentages (22-62%). Performing a multivariate analysis, we found that the frequency of homophobia was lower for the following variables: the female gender (PRa=0.74; 95% CI, 0.61-0.92; p=0.005), studying at a university in Lima (PRa=0.57; 95% CI, 0.43-0.75; p<0.001), professing the Catholic religion (PRa=0.53; 95% CI, 0.37-0.76;p<0.001), knowing a homosexual (PRa=0.73; 95% CI, 0.60-0.90; p=0.003) and having treated a homosexual patient (PRa=0.76; 95% CI, 0.59-0.98; p=0.036). In contrast, the frequency of homophobia increased in male chauvinists (PRa=1.37; 95% CI, 1.09-1.72; p=0.007), adjusted by four variables. Conclusions: Homophobia was less common in women, in those who study in the capital, those who profess Catholicism and those who know/have treated a homosexual. In contrast, male chauvinists were more homophobic.

Factors associated with homophobia in medical students from eleven Peruvian universities. / Factores asociados a la homofobia en estudiantes de Medicina de once universidades peruanas.

BACKGROUND: The consequences of homophobia can affect the integrity, mental and physical health of homosexual individuals in society. There are few studies in Peru that have evaluated homophobia in the medical student population. OBJECTIVE: To establish the social, educational and cultural factors associated with homophobia among Peruvian medical students. METHODS: A cross-sectional analytical study was conducted in 12 medicine schools in Peru. Homophobia was defined according to a validated test, which was associated with other variables. Statistical associations were identified. RESULTS: The lowest percentages of homophobic students (15-20%) were found in the four universities in Lima, while universities in the interior of the country had the highest percentages (22-62%). Performing a multivariate analysis, we found that the frequency of homophobia was lower for the following variables: the female gender (PRa=0.74; 95% CI, 0.61-0.92; p=0.005), studying at a university in Lima (PRa=0.57; 95% CI, 0.43-0.75; p<0.001), professing the Catholic religion (PRa=0.53; 95% CI, 0.37-0.76; p<0.001), knowing a homosexual (PRa=0.73; 95% CI, 0.60-0.90; p=0.003) and having treated a homosexual patient (PRa=0.76; 95% CI, 0.59-0.98; p=0.036). In contrast, the frequency of homophobia increased in male chauvinists (PRa=1.37; 95% CI, 1.09-1.72; p=0.007), adjusted by four variables. CONCLUSIONS: Homophobia was less common in women, in those who study in the capital, those who profess Catholicism and those who know/have treated a homosexual. In contrast, male chauvinists were more homophobic.

Cumplimiento de la norma técnica de salud para la atención integral de la tuberculosis el Centro de Salud "Atusparias" del Distrito de José Leonardo Ortiz, enero ­ junio del 2016 / Compliance of the technical health standard for the integral care of tuberculosis the "Atusparias" Health Center of the District Jose Leonardo Ortiz, january - june 2016

Objetivo: Determinar el Cumplimiento de la norma técnica de salud para la atención integral de la Tuberculosis en el Centro de Salud Atusparias en el distrito de José Leonardo Ortiz, Enero - Junio 2016. Material y métodos: Se llevó a cabo un análisis de datos de fuente secundaria, mediante la técnica check list utilizando una ficha para recolección de datos, empleando el libro de registro de sintomáticos respiratorios, libro de terapia de 1era y 2da línea, así como las tarjetas de control de tratamiento para pacientes TB diagnosticada de los meses Enero - Junio del 2016. La muestra de estudio estuvo constituida por 160 Sintomáticos Respiratorios. Resultados: los pacientes BK positivos predominó el sexo femenino, las edades entre 30 - 59 años, correspondientes a la etapa de vida adulta; el porcentaje de Sintomáticos Respiratorios examinados con dos muestras de esputo fue 43,3%; el porcentaje de visitas domiciliarias a los pacientes con diagnóstico de BK positivo fue 34,78%, el número de contactos examinados en relación a los contactos censados fue 41,09% del total. Conclusión: el 53% de incumplimiento de la Norma Técnica de Salud para la atención integral de la Tuberculosis en relación a los criterios de control de contactos, seguimiento diagnóstico y visita domiciliaria.

Amazon River dissolved load: temporal dynamics and annual budget from the Andes to the ocean.

The aim of the present study is to estimate the export fluxes of major dissolved species at the scale of the Amazon basin, to identify the main parameters controlling their spatial distribution and to identify the role of discharge variability in the variability of the total dissolved solid (TDS) flux through the hydrological cycle. Data are compiled from the monthly hydrochemistry and daily discharge database of the "Programa Climatologico y Hidrologico de la Cuenca Amazonica de Bolivia" (PHICAB) and the HYBAM observatories from 34 stations distributed over the Amazon basin (for the 1983-1992 and 2000-2012 periods, respectively). This paper consists of a first global observation of the fluxes and temporal dynamics of each geomorphological domain of the Amazon basin. Based on mean interannual monthly flux calculations, we estimated that the Amazon basin delivered approximately 272 × 10(6) t year(-1) (263-278) of TDS during the 2003-2012 period, which represents approximately 7 % of the continental inputs to the oceans. This flux is mainly made up by HCO3, Ca and SiO2, reflecting the preferential contributions of carbonate and silicate chemical weathering to the Amazon River Basin. The main tributaries contributing to the TDS flux are the Marañon and Ucayali Rivers (approximately 50 % of the TDS production over 14 % of the Amazon basin area) due to the weathering of carbonates and evaporites drained by their Andean tributaries. An Andes-sedimentary area-shield TDS flux (and specific flux) gradient is observed throughout the basin and is first explained by the TDS concentration contrast between these domains, rather than variability in runoff. This observation highlights that, under tropical context, the weathering flux repartition is primarily controlled by the geomorphological/geological setting and confirms that sedimentary areas are currently active in terms of the production of dissolved load. The log relationships of concentration vs discharge have been characterized over all the studied stations and for all elements. The analysis of the slope of the relationship within the selected contexts reveals that the variability in TDS flux is mainly controlled by the discharge variability throughout the hydrological year. At the outlet of the basin, a clockwise hysteresis is observed for TDS concentration and is mainly controlled by Ca and HCO3 hysteresis, highlighting the need for a sampling strategy with a monthly frequency to accurately determine the TDS fluxes of the basin. The evaporite dissolution flux tends to be constant, whereas dissolved load fluxes released from other sources (silicate weathering, carbonate weathering, biological and/or atmospheric inputs) are mainly driven by variability in discharge. These results suggest that past and further climate variability had or will have a direct impact on the variability of dissolved fluxes in the Amazon. Further studies need to be performed to better understand the processes controlling the dynamics of weathering fluxes and their applicability to present-day concentration-discharge relationships at longer timescales.

Spatial-temporal variation of dissolved inorganic material in the Amazon basin / Variação espaço-temporal do material inorgânico dissolvido na bacia Amazônica

The Amazon River basin is important in the contribution of dissolved material to oceans (4% worldwide). The aim of this work was to study the spatial and the temporal variability of dissolved inorganic materials in the main rivers of the Amazon basin. Data from 2003 to 2011 from six gauging stations of the ORE-HYBAM localized in Solimões, Purus, Madeira and Amazon rivers were used for this study. The concentrations of Ca2+, Na+, K+, Mg2+, Cl-, SO4 -2, HCO3 - and SiO2 were analyzed. At the stations of Solimões and Amazon rivers, the concentrations of Ca2+, Mg2+, HCO3 - and SO4 -2 had heterogeneous distribution over the years and did not show seasonality. At the stations of Madeira river, the concentration of these ions had seasonality inversely proportional to water discharge (dilution-concentration effect). Similar behavior was observed for the concentrations of Cl- and Na+ at the stations of the Solimões, Amazon and Madeira rivers, indicating almost constant release of Cl- and Na+ fluxes during the hydrological cycle. K+ and SiO2 showed almost constant concentrations throughout the years and all the stations, indicating that their flows depend on the river discharge variation. Therefore, the temporal variability of the dissolved inorganic material fluxes in the Solimões and Amazon rivers depends on the hydro-climatic factor and on the heterogeneity of the sources. In the Madeira and Purus rivers there is less influence of these factors, indicating that dissolved load fluxes are mainly associated to silicates weathering. As the Solimões basin contributes approximately 84% of the total flux of dissolved materials in the basin and is mainly under the influence of a hydro-climatic factor, we conclude that the temporal variability of this factor controls the temporal variability of the dissolved material fluxes of the Amazon basin.

A bacia do rio Amazonas é importante no aporte de material dissolvido para o oceano (4% a nível mundial). O objetivo deste trabalho foi estudar a variabilidade espaço-temporal do material inorgânico dissolvido nos principais rios da bacia Amazônica, para o qual foram utilizados dados entre 2003 e 2011 de seis estações hidrológicas do ORE-HYBAM localizadas nos rios Solimões, Purus, Madeira e Amazonas, analisados Ca2+, Na+, K+, Mg2+, Cl-, SO4 -2, HCO3 - e SiO2. Nas estações do rio Solimões e Amazonas as concentrações de Ca2+, Mg2+, HCO3 - e SO4 -2 tiveram distribuição heterogênea ao longo dos anos e não apresentaram sazonalidade. Nas estações do rio Madeira a concentração desses íons mostraram sazonalidade inversamente proporcional à vazão (efeito diluição-concentração). Comportamento similar tiveram Cl- e Na+ nas estações dos rios Solimões, Amazonas e Madeira, indicando liberação quase constante desses fluxos ao longo do ciclo hidrológico. K+ e SiO2 apresentaram concentrações quase constantes ao longo dos anos e entre as estações, indicando que seus fluxos dependem da variação da vazão. Portanto, a variação temporal do fluxo de material inorgânico dissolvido no rio Solimões e Amazonas depende do fator hidroclimatológico e da heterogeneidade das fontes. Nos rios Madeira e Purus há menor influência desses fatores, o que evidencia maior aporte dos silicatos. Como a bacia do Solimões aporta aproximadamente 84% do fluxo total de material dissolvido na bacia e está sob influência, principalmente, do fator hidroclimático, pode-se concluir que a variabilidade temporal desse fator controla a temporalidade dos fluxos do material dissolvido na bacia Amazônica.