Brain afferents to the lateral caudal ventrolateral medulla : a retrograde and anterograde tracing study in the rat

The ventrolateral medulla (VLM) modulates autonomic functions, motor reactions and pain responses. The lateralmost part of the caudal VLM (VLMlat) was recently shown to be the VLM area responsible for pain modulation. In the present study, the brain sources of VLMlat afferent fibers were determined by tract-tracing techniques. Following injection of cholera toxin subunit B into the VLMlat, retrogradely labeled neurons in the forebrain occurred at the somatosensory, insular, motor, limbic and infralimbic cortices, and at the central amygdaloid nucleus. Retrogradely labeled neurons in diencephalic regions were observed in the lateral hypothalamus, posterior hypothalamus and paraventricular nucleus. In the brainstem, retrograde labeling occurred at the periaqueductal gray, red nucleus, parabrachial area, nucleus raphe magnus, nucleus tractus solitarii, lateral reticular nucleus and dorsal and ventral medullary reticular formation. In the cerebellum, retrogradely labeled neurons occurred at the lateral nucleus. Following injections of the anterograde tracer biotinylated dextran amine (BDA) into the lateral hypothalamus or paraventricular nucleus, anterogradely labeled fibers were mainly observed in the VLMlat. Injections of BDA into the periaqueductal gray, red nucleus or lateral nucleus of the cerebellum resulted in anterograde labeling in the VLMlat and lateral reticular nucleus. The present study gives an account of the brain regions putatively involved in triggering the modulatory actions elicited from the VLMlat. These include areas committed to somatosensory processing, autonomic control, somatic and visceral motor activity and affective reactions. The findings suggest that the VLMlat may play a major homeostatic role in the integration of nociception with other brain functions.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/NSE/38952/2001.Fundação Calouste Gulbenkian (FCG) – Pain Program

Treatment and seroconversion in a cohort of children suffering from recent chronic Chagas infection in Yoro, Honduras

Between 1999-2002, Médécins Sans Frontières-Spain implemented a project seeking to determine the efficacy and safety of benznidazole in the treatment of recent chronic Chagas disease in a cohort of seropositive children in the Yoro Department, Honduras. A total of 24,471 children were screened for Trypanosoma cruzi IgG antibodies through conventional enzyme-linked immunosorbent assays (ELISA) on filter paper. Recombinant ELISA (0.93% seroprevalence) showed 256 initially reactive cases, including 232 confirmed positive cases. Of these, 231 individuals were treated with benznidazole (7.5 mg/kg/day) for 60 days and were followed with a strict weekly medical control and follow-up protocol. At the end of the project, 229 patients were examined by the Honduras Secretariat of Health for post-treatment serological assessments; 88.2% seroconverted after 18 months and 93.9% seroconverted after three years. No differences were found in the seroconversion rates according to age or sex. Most of the side effects of the treatment were minor. These results support the argument that in areas where T. cruzi I is predominant and in areas affected by T. cruzi II, when vector transmission has been interrupted, Chagas disease diagnosis and treatment are feasible, necessary and ethically indisputable

Impacts of cash transfer and “cash plus” programs on self- perceived stress in Africa:Evidence from Ghana, Malawi, and Tanzania

Poverty and poor mental health are closely linked. Cash transfers have significantly expanded globally. Given their objectives around poverty reduction and improving food security, a major chronic stressor in Africa, cash transfers may affect mental health outcomes. We examine impacts of three large-scale government cash transfer or cash plus programs in Ghana, Malawi, and Tanzania on self-perceived stress using an innovative, newly adapted measure for rural African settings. Linear regression models were used to estimate treatment impacts. We find that cash transfers reduced self-perceived stress in Malawi, but programs in Ghana and Tanzania had no impacts on self-perceived stress. These mixed findings, combined with recent reviews on cash transfers and mental health, suggest that cash transfers may play a role in improving mental health. However, cash alone may not be sufficient to overcome many challenges related to poverty, and complementary programming may also be needed to improve mental health.</p

Simple and Effective Multi-Paragraph Reading Comprehension

We consider the problem of adapting neural paragraph-level question answering models to the case where entire documents are given as input. Our proposed solution trains models to produce well calibrated confidence scores for their results on individual paragraphs. We sample multiple paragraphs from the documents during training, and use a shared-normalization training objective that encourages the model to produce globally correct output. We combine this method with a state-of-the-art pipeline for training models on document QA data. Experiments demonstrate strong performance on several document QA datasets. Overall, we are able to achieve a score of 71.3 F1 on the web portion of TriviaQA, a large improvement from the 56.7 F1 of the previous best system.Comment: 11 pages, updated a referenc

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

BACKGROUND: There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. METHODS: This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). RESULTS: 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. CONCLUSIONS: In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients

Visceral leishmaniasis and HIV co-infection in Bihar, India: long-term effectiveness and treatment outcomes with liposomal amphotericin B (AmBisome).

BACKGROUND: Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012. METHODS AND PRINCIPAL FINDINGS: Intravenous AmBisome (20-25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4-10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4-51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7-14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64-66% reduced risk of mortality and 75% reduced risk of relapse. SIGNIFICANCE: This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed

Sucrose hydrolysis catalyzed by auto-immobilized invertase into intact cells of Cladosporium cladosporioides

The enzyme known as invertase (E.C. 3.2.1.26 - \u3b2-D-fructofuranosidase) catalyzes the sucrose hydrolysis producing an equimolar mixture of glucose and fructose named inverted sugar. The fungus Cladosporium cladosporioides has invertase as its constituent. Hence, its use as a natural immobilized support for the invertase produces interesting results for the enzyme. The present work has the objective of determining the optimum operational conditions of auto-immobilized invertase, as well as its kinetic parameters (KM and Vmax). A complete 23 factorial planning was done for the evaluation of such parameters. Temperature, pH and agitation level were the studied variables. The hydrolysis percentage was the monitored result. Batch tests in optimum conditions were done to determine the kinetic parameters. Temperature of 70\ub0C, pH 6 and agitation of 170 rpm were the established conditions for the hydrolysis process. The auto-immobilized invertase presented a KM of 447 mM and Vmax of 2,805 mmol/min

Atividade antibacteriana do óleo essencial de origanum vulgare frente a staphylococcus sp. Isolados do queijo minas artesanal / Antibacterial activity of origanum vulgare essential oil in front of staphylococcus sp. Isolates of minas artesanal cheese

 O orégano (Origanum vulgare) é um condimento advindo do mediterrâneo muito utilizado na culinária com diversas propriedades terapêuticas conhecidas. O óleo essencial do orégano apresenta compostos fenólicos com propriedades medicinais bem conhecidas como a antimicrobiana e antioxidante apresentando o carvacrol e p-cimeno como seus principais constituintes. Realizou-se no presente trabalho, o estudo da capacidade bactericida e bacteriostática do óleo essencial do orégano frente a Staphylococcus sp. isolados do queijo. Extraiu-se o óleo essencial pelo método de hidrodestilação. O teste de sensibilidade ao óleo essencial de orégano foi realizado em duplicata. Para a definição da CIM foram preparados tubos nas diluições de 133,3 µl/mL, 66,6 µl/ml, 33,3 µl/ml, 16,6 µl/mL e 8,3 µl/mL, além dos controles positivos e negativos. Na concentração de 133,3 µl/ml não houve crescimento microbiano. Após a leitura da CIM, na concentração em que houve resultado negativo (isto é, não houve crescimento bacteriano por inibição do óleo), retirou-se uma alíquota de seus tubos para definição da CBM. Realizou-se o teste de difusão em disco também com antibióticos convencionais e leitura dos halos de ambas as placas, além da leitura do CBM. Os resultados foram efetivos e satisfatórios na concentração de 133,3 uL/mL tanto para a ação bacteriostática quanto bactericida frente a Staphylococcus sp. isolado do Queijo e S. aureus ATCC