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BACKGROUND: The glial cell line-derived neurotrophic factor has a potent neuroprotective action on mesencephalic dopamine neurons, which are progressively lost in Parkinson's disease. Intrastriatal administration of this factor is a promising therapy for Parkinson's disease. Glial cell line-derived neurotrophic factor is naturally produced in restricted cerebral regions, such as the striatum, septum, and thalamus; however, its effects in the adult brain remain under debate. OBJECTIVES: We sought to clarify the physiologic role of endogenous glial cell line-derived neurotrophic factor in the survival of catecholaminergic neurons of the substantia nigra pars compacta and the locus coeruleus in adult mice. METHODS: We used 2 new Cre recombinase-based mouse models to delete a floxed-glial cell line-derived neurotrophic factor gene. The first model had Cre expression in the parvalbumin expressing interneurons, as these cells represent the major source of striatal glial cell line-derived neurotrophic factor. The second model was an estrogen receptor 2-based inducible Cre triggered by tamoxifen at 2 months of age. RESULTS: We found that the floxed-glial cell line-derived neurotrophic factor gene was resilient to ablation by Cre-induced recombination and that parvalbumin-driven Cre was particularly inefficient to do so. The inducible-Cre model allowed an average 70% to 80% reduction in glial cell line-derived neurotrophic factor messenger ribonucleic acid and protein in striatum and septum with moderate significant loss of catecholamine neurons in the nigrostriatal pathway and, more markedly, in the locus coeruleus. This was accompanied with mild locomotor decline. CONCLUSIONS: Our data support qualitatively the view that brain glial cell line-derived neurotrophic factor is needed for the maintenance of adult central catecholaminergic neurons. © 2020 International Parkinson and Movement Disorder Society.
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Fármacos Neuroprotetores , Doença de Parkinson , Animais , Corpo Estriado , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Camundongos , Neostriado , Neurônios , Substância NegraRESUMO
We announce the genome sequencing, assembly, and annotation of the OLsAu1 strain and its taxonomic assignment to Pseudomonas yamanorum. The isolate comes from a wild edible ectomycorrhizal Lactarius sp. mushroom in the Abies forest. There is information regarding the strain's ability to promote plant growth, indicating its potential application in forestry.
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OBJECTIVE: This study reports on food insecurity (FI) amidst the COVID-19 pandemic. PARTICIPANTS AND METHODS: College students in four regions of the US completed the two-item validated Hunger Vital Sign™ screening tool on Qualtrics. RESULTS: FI increased significantly after March 2020 among US students (worry about food running out: 25% to 35%; food did not last: 17% to 21%) with significant regional increase in the Midwest and South. An adjusted multivariable logistic regression model indicated students that ran out of food were significantly at greater odds of experiencing hardship with paying bills (AOR: 5.59, 95% CI =3.90-8.06). CONCLUSIONS: The findings identified an increase in the prevalence of FI among college students during the pandemic. Suggestions of how to address FI are discussed.
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Students at higher institutions of learning are more susceptible to psychosocial problems compared to the general public. These may further be exacerbated by the measures put in place to curb the spread of COVID-19. This mixed methods study examined the factors associated with the psychosocial impact of COVID-19 on students' financial stability, interpersonal relationships and worries related to achieving academic milestones. Data comprised of a series of closed and open-ended questions collected via Qualtrics from students in the United States and Africa (Central and West). The quantitative data were analyzed using frequency counts, percentages and chi-square, while the qualitative data was analyzed using thematic content analysis. More than 90% of the students resided in the United States, 72.5% were females and 78.4% were undergraduates. Financial hardship was experienced by 26.4% of the students, 55.8% indicated that COVID-19 negatively affected their relationship with friends and over 40% worried over delays in achieving academic milestones. Continent of residence, employment status and financial hardship were significantly associated with the negative impact of COVID-19 on one or more of the students' relationships and with worries about achieving academic milestones. Qualitative data support the findings that financial hardship contributed to experience of psychological distress by students. It also revealed negative (compromised relationships - broken or fractured relationships and loneliness) and positive (bonding) impact of COVID-19 on interpersonal relationships. School administrators should provide students with resources to access economic relief packages and tele-counseling services to help meet their financial and psychosocial support needs amidst COVID-19.
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Background: Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts. Methods: Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD. Results: The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HRHispanic = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; HNHW = 1.38, 99% CI = 1.33 to 1.43; 2-sided P heterogeneity = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking. Conclusions: We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.
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Neoplasias da Mama/etnologia , Sobreviventes de Câncer , Doenças Cardiovasculares/etnologia , Hispânico ou Latino , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer/estatística & dados numéricos , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Intervalos de Confiança , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Doenças Linfáticas/etnologia , Doenças Linfáticas/etiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Utah , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
Administration of recombinant glial cell line-derived neurotrophic factor into the putamen has been tested in preclinical and clinical studies to evaluate its neuroprotective effects on the progressive dopaminergic neuronal degeneration that characterizes Parkinson's disease. However, intracerebral glial cell line-derived neurotrophic factor infusion is a challenging therapeutic strategy, with numerous potential technical and medical limitations. Most of these limitations could be avoided if the production of endogenous glial cell line-derived neurotrophic factor could be increased. Glial cell line-derived neurotrophic factor is naturally produced in the striatum from where it exerts a trophic action on the nigrostriatal dopaminergic pathway. Most of striatal glial cell line-derived neurotrophic factor is synthesized by a subset of GABAergic interneurons characterized by the expression of parvalbumin. We sought to identify molecular targets specific to those neurons and which are putatively associated with glial cell line-derived neurotrophic factor synthesis. To this end, the transcriptomic differences between glial cell line-derived neurotrophic factor-positive parvalbumin neurons in the striatum and parvalbumin neurons located in the nearby cortex, which do not express glial cell line-derived neurotrophic factor, were analysed. Using mouse reporter models, we have defined the genomic signature of striatal parvalbumin interneurons obtained by fluorescence-activated cell sorting followed by microarray comparison. Short-listed genes were validated by additional histological and molecular analyses. These genes code for membrane receptors (Kit, Gpr83, Tacr1, Tacr3, Mc3r), cytosolic proteins (Pde3a, Crabp1, Rarres2, Moxd1) and a transcription factor (Lhx8). We also found the proto-oncogene cKit to be highly specific of parvalbumin interneurons in the non-human primate striatum, thus highlighting a conserved expression between species and suggesting that specific genes identified in mouse parvalbumin neurons could be putative targets in the human brain. Pharmacological stimulation of four G-protein-coupled receptors enriched in the striatal parvalbumin interneurons inhibited Gdnf expression presumably by decreasing cyclic adenosine monophosphate formation. Additional experiments with pharmacological modulators of adenylyl cyclase and protein kinase A indicated that this pathway is a relevant intracellular route to induce Gdnf gene activation. This preclinical study is an important step in the ongoing development of a specific pro-endo-glial cell line-derived neurotrophic factor pharmacological strategy to treat Parkinson's disease.
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INTRODUCTION: Mortality rates for coronary heart disease (CHD) have declined markedly since the early 1970s. However, CHD remains the number one cause of death in the United States. The decline in mortality has been attributed to declines in CHD risk factors (tobacco use, hypertension) and the increase in protective behaviors (exercise, weight control). Medical interventions may have also contributed to the decline in mortality. Despite these declines in mortality, racial disparities persist between Blacks and Whites. The purpose of this study was to examine the differences in receipt of cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. METHODS: Data from the National Hospital Discharge Survey were used for the analysis. Patients who were Black or White and > or = 40 years of age were included. Independent variables included age at discharge, sex, race, and insurance coverage. Multivariate logistic regression was used to derive odds ratios for the receipt of the three procedures by age group, sex, insurance type, and race. RESULTS: Significant differences (P < .05) in the odds of receipt of all of cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft were found by age group, insurance type, sex, and race. While the disparities persisted from 1979 to 2004, the magnitude of the differences decreased during this time period. CONCLUSION: Disparities by race, sex, and insurance type existed in the receipt of three cardiac procedures. Although differences are narrowing over time, further in-depth studies are needed to elucidate the patient, physician, and healthcare system factors associated with the disparity in receipt of these beneficial procedures.
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Angioplastia Coronária com Balão/estatística & dados numéricos , População Negra/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Doença das Coronárias/terapia , Disparidades em Assistência à Saúde , População Branca/estatística & dados numéricos , Adulto , Idoso , Doença das Coronárias/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia , Revisão da Utilização de Recursos de SaúdeRESUMO
OBJECTIVES: To explore intrapersonal, social environmental, and physical environmental influences that promote or impede total physical activity (TPA) among Latinas in Lee County, Florida. METHODS: In-depth interviews (n=41) and face-to-face surveys (n=358). RESULTS: Women who worked outside the home, had positive attitudes about activity, perceived themselves to have access to activity facilities, and perceived their neighborhood to be safe reported higher TPA. Women who had more education and whose health information source was radio had lower TPA. CONCLUSIONS: Intrapersonal and environmental factors influence TPA levels among Latinas. Segmenting Latina groups using these factors may promote more involvement in physical activity through targeted programs and messages.
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Hispânico ou Latino/estatística & dados numéricos , Atividade Motora , Meio Social , Adulto , Demografia , Feminino , Nível de Saúde , Humanos , América Latina/epidemiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Prostate Cancer (CaP) is the most commonly diagnosed cancer among Cameroonian men. Due to inadequate infrastructure, record keeping, and resources, little is known about its true burden on the population. There are rural/urban disparities with regards to awareness, screening, treatment, and survivorship. Furthermore, use of traditional medicine and homeopathic remedies is widespread, and some men delay seeking conventional medical treatment until advanced stages of CaP. This study examined the perceptions, beliefs, and practices of men in Cameroon regarding late stage CaP diagnoses; identified factors that influence screening decision; and ascertained how men decided between traditional or conventional medicine for CaP diagnosis and treatment. Semistructured focus groups were used to collect data from men in Bamenda, Cameroon. Qualitative data analysis was used to analyze transcripts for emerging themes and constructs using a socio-ecological framework. Twenty-five men participated in the study, with an average age of 59. Most of the participants had never received a prostate screening recommendation. Socioeconomic status, local beliefs, knowledge levels, awareness of CaP and screening methods, and stigma were prominent themes. A significant number of Cameroonian men receive late stage CaP diagnosis due to lack of awareness, attitudes, cultural beliefs, self-medication, and economic limitation. To effectively address these contributing factors to late stage CaP diagnosis, a contextually based health education program is warranted and should be tailored to fill knowledge gaps about the disease, dispel misconceptions, and focus on reducing barriers to utilization of health services.
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Tomada de Decisões , Diagnóstico Tardio/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Comportamentos Relacionados com a Saúde/etnologia , Educação em Saúde/organização & administração , Adulto , Idoso , Camarões , Estudos de Coortes , Cultura , Diagnóstico Tardio/mortalidade , Países em Desenvolvimento , Detecção Precoce de Câncer/estatística & dados numéricos , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Cooperação do Paciente/estatística & dados numéricos , Percepção , Medição de Risco , Fatores Socioeconômicos , Taxa de SobrevidaRESUMO
This paper identifies naturally occurring lifestyle and self-care practices in managing type 2 diabetes mellitus that are associated with good glycemic control. In-depth, qualitative interviews were conducted in Guadalajara, Mexico, with 31 matched pairs of good and poor control diabetic patients (n=62), who were matched on their duration of disease and use of medications. While many themes were listed by both groups, a comparison of the responses indicated that themes of daily exercise with a preference for walking, eating beef and milk rather than chicken and fish, economic issues, and emotional issues distinguished poor-control patients. Good-control patients were more likely to have a negative reaction to their initial diagnosis, take a more comprehensive approach to control, eat only two meals a day (plus snacks), use noncaloric beverages to satisfy desires for more food, and know what their blood sugar levels should be.
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Atitude Frente a Saúde , Diabetes Mellitus Tipo 2 , Estilo de Vida , Autocuidado/estatística & dados numéricos , Idoso , Automonitorização da Glicemia , Feminino , Hispânico ou Latino , Humanos , Masculino , México , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados UnidosRESUMO
INTRODUCTION: Although less than 3% of medical schools are considered Historically Black Colleges and Universities (HBCU), they have played a significant role in the education of Black physicians. METHODS: The Association of American Medical Colleges (AAMC) databases were used to obtain faculty and student demographic data from 2003-2013. We analyzed racial distributions of faculty and students at HBCU medical schools compared with all other medical schools and calculated correlations between rates of Black chairs, faculty, and students. RESULTS: Although HBCUs represent 2.4% of medical colleges, they house 31% of Black chairs, 10% of Black faculty and 14% of Black students. A significant (a* < .002) positive correlation was found between rates of Black chairs and students. CONCLUSIONS: Black chairs are associated with higher percentages of Black students. Medical colleges may find that increasing the number of Black chairs increases the number of Black medical students.
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Negro ou Afro-Americano/estatística & dados numéricos , Docentes de Medicina/estatística & dados numéricos , Faculdades de Medicina/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Diversidade Cultural , HumanosRESUMO
Gender difference in Parkinson's disease (PD) suggests that female sex steroids may promote dopaminergic neuron survival and protect them from degeneration. The glial cell line-derived neurotrophic factor (GDNF) is believed to be dopaminotrophic; thus it is considered as a potential therapeutic target in PD. Additionally, GDNF is endogenously synthetized in the caudate/putamen of humans and striatum in rodents. A neuroprotective role of estrogens on the nigrostriatal pathway via the stimulation of GDNF has been proposed. Since the GDNF-producing parvalbumin (Parv) interneurons express the estrogen receptor alpha in the mouse striatum, we sought to determine whether ectopic estrogenic compound modulates the GDNF synthesis in mice. Using an ovariectomized-estradiol (E2) replacement regimen, which reliably generates a rise of plasma estradiol, we assessed the effects of different levels of E2 on the activation of striatal neuronal populations, and GDNF production. A strong correlation was found between plasma E2 and the expression of the immediate early gene cFos in the striatum, as well as in other cortical regions. However, moderate and high E2 treatments failed to induce any striatal GDNF mRNA and protein synthesis. High E2 only stimulates cFos induction in a low percentage of striatal Parv neurons whereas the majority of cFos-positive cells are medium spiny neurons. Activation of these projecting neurons by E2 suggests a role of circulating sex steroids in the modulation of striatal neural pathways.
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Estradiol/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Animais , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Imunoensaio , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To explore the perspectives of various stakeholders on whether an HBCU has the resources to establish a farm-to-university program that can improve fruits and vegetables intake among African American students. Additionally, this study assessed students' satisfaction with fruits and vegetables served in University dining halls, and their desire for changes in policies to increase local fruits and vegetables access on campus. METHODS: This study employed a mixed method data collection strategy. Semi-structured interviews were used to explore the stakeholders' perspectives and self-administered questionnaires were used to assess students' satisfaction with fruits and vegetables and desire for policy changes. RESULTS: Barriers reported by both food service administrators and farmers were cost and variation in supply and demand. Students expressed lack of satisfaction with fresh produce served in campus dining halls and a desire for change in policies to increase local fruits and vegetables access on campus. CONCLUSION: While there is student desire for improved access to fresh produce on campus, there are perceived barriers to overcome. University partnerships are needed to address the desired nutritional improvements.
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Dieta/métodos , Abastecimento de Alimentos/métodos , Universidades/organização & administração , Adolescente , Adulto , Negro ou Afro-Americano , Feminino , Frutas , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Política Nutricional , Estudantes/psicologia , Inquéritos e Questionários , Verduras , Adulto JovemRESUMO
Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia.
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OBJECTIVE: To explore causal explanations of obesity among African-American women of diverse weight across the life spectrum. METHODS: In-depth interviews were conducted with adult African-American women of healthy weight (N = 10), overweight (N = 10), and obese weight (N = 20) to evaluate the relationship between causal explanations of obesity and weight. RESULTS: Generally overlooked dimensions of health definitions were discovered. Differences in weight definitions were detected between women of different weights. Terminology, symptoms, and solutions to obesity were detected between the women of different weights and public health recommendations. CONCLUSION: Identified causal discrepancies will help bridge the disconnection between public health recommendations and African-American women's perceptions with tailored interventions.
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Negro ou Afro-Americano/psicologia , Letramento em Saúde , Obesidade/etnologia , Adulto , Idoso , Competência Cultural , Feminino , Florida , Humanos , Controle Interno-Externo , Entrevistas como Assunto , Pessoa de Meia-Idade , Pesquisa Qualitativa , Apoio Social , Estresse Psicológico , Adulto JovemRESUMO
An enzyme-linked immunosorbent assay to quantify the mAb CB.Hep-1 during downstream purification process was standardized and validated. This assay is characterized by a short time of incubation at high temperature, allowing the detection of this antibody with high specificity and sensitivity. Detection of antigen-antibody reaction was achieved using a horseradish peroxidase conjugated anti-mouse IgG whose enzyme activity was revealed with o-phenylenediamine substrate. The immunoassay is linear in a range between 3.12 and 50 ng/mL, with a recovery of 98.55-107.62%. According to results, it is possible to estimate the mAb CB.Hep-1 concentration with high precision and reproducibility. The intra- and interassay coefficient of variation ranged from 0.25 to 8.64% and 1.84 to 9.43%, respectively. Significant differences were not observed in the plant-derived antibody quantification by HRP-ELISA and PhoA-ELISA (n=18), demonstrating that plant endogenous peroxidases do not produce interferences in the quantification of this molecule. Therefore, both antibodies can be tested with the same immunoassay with high precision, specificity and accuracy during their respective purification processes without interference of the buffers and sample characteristics.
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Anticorpos Monoclonais/análise , Antígenos de Superfície da Hepatite B/imunologia , Planticorpos/análise , Animais , Anticorpos Monoclonais/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática/métodos , Camundongos , Camundongos Endogâmicos BALB C , Pichia/imunologia , Planticorpos/isolamento & purificação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. METHODS: A retrospective case-control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. RESULTS: Women with breast carcinoma had a mean DRC of 5.6% +/- 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P<0.001) in DRC when compared with the control group (DRC=8.7% +/- 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR]=4.1), maternal lineage (OR=5.5), and maternal (OR=12.4) history of breast carcinoma were found to be the only statistically significant (P<0.05) risk factors associated with the disease. CONCLUSIONS: The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility.
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Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Reparo do DNA/genética , Adulto , Idoso , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Luciferases/análise , Linfócitos/sangue , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Se comunicó el caso de una paciente con diagnóstico de coagulación intravascular diseminada, de tipo fulminante, cuya causa resultó ser una leucemia promielocítica aguda, de la variedad hipergranular. Se observó, clínicamente, un comportamiento agresivo de la enfermedad que ocasionó la muerte del paciente, en 72 h, por hemorragias viscerales masivas