Investigation of the pathways related to intrinsic miltefosine tolerance in Leishmania (Viannia) braziliensis clinical isolates reveals differences in drug uptake

In Brazil, cutaneous leishmaniasis is caused predominantly by L. (V.) braziliensis. The few therapeutic drugs available exhibit several limitations, mainly related to drug toxicity and reduced efficacy in some regions. Miltefosine (MF), the only oral drug available for leishmaniasis treatment, is not widely available and has not yet been approved for human use in Brazil. Our group previously reported the existence of differential susceptibility among L. (V.) braziliensis clinical isolates. In this work, we further characterized three of these isolates of L. (V.) braziliensis chosen because they exhibited the lowest and the highest MF half maximal inhibitory concentrations and were therefore considered less tolerant or more tolerant, respectively. Uptake of MF, and also of phosphocholine, were found to be significantly different in more tolerant parasites compared to the less sensitive isolate, which raised the hypothesis of differences in the MF transport complex Miltefosine Transporter (MT)-Ros3. Although some polymorphisms in those genes were found, they did not correlate with the drug susceptibility phenotype. Drug efflux and compartmentalization were similar in the isolates tested, and amphotericin B susceptibility was retained in MF tolerant parasites, suggesting that increased fitness was also not the basis of observed differences. Transcriptomic analysis revealed that Ros3 mRNA levels were upregulated in the sensitive strain compared to the tolerant ones. Increased mRNA abundance in more tolerant isolates was validated by quantitative PCR. Our results suggest that differential gene expression of the MT transporter complex is the basis of the differential susceptibility in these unselected, naturally occurring parasites

Determinants of frequency and longevity of hospital encounters' data use

<p>Abstract</p> <p>Background</p> <p>The identification of clinically relevant information enables improvement in user interfaces and in data management. However, it is difficult to identify what information is important in daily clinical care, and what is used occasionally. This study aims to determine for how long clinical documents are used in a Hospital Information System (HIS).</p> <p>Methods</p> <p>The access logs of 3 years of usage of a HIS were analysed concerning report departmental source, type of hospital encounter, and inpatient encounter ICD-9-CM main diagnosis. Reports median life indicates the median time elapsed between information creation and its usage. The models that better explains report views over time were explored.</p> <p>Results</p> <p>The number of report views in the study period was 656 583. Fifty two percent of the reports viewed by medical doctors in emergency encounters were from previous encounters - 21% at outpatient attendance, 19% in inpatient (wards) and 12% during emergency encounters. In an inpatient setting, 20% of the reports viewed were produced in previous encounters. The median life of information in documents is 1.5 days for emergency, 4.8 days for inpatient and 37.8 days for outpatient encounters. Immune-haemotherapy reports reach their median lives faster (7 days) than clinical pathology (15 days), gastroenterology (80 days) and pathology (118 days). The median life of reports produced in inpatient encounters varied from 36 days for neoplasms as the main diagnosis to 0.7 days for injury and poisoning. The model with the best fit (R²> 0.9) was the exponential.</p> <p>Conclusions</p> <p>The usage of past patient information varied significantly according to patient age, type of information, type of hospital encounter and medical cause (main diagnosis) for the encounter. The exponential model is a good fit to model how the reports are seen over time, so the design of user interfaces and repository management algorithms should take it in consideration.</p

Prebiotics, Probiotics, Synbiotics and Functional Foods in Control and Treatment of Type II Diabetes Mellitus and Colorectal Cancer

Prebiotics, probiotics and synbiotics are components that enhance human health by several mechanisms. Patients suffering from type II diabetes mellitus (T2DM) and colorectal cancer have seen benefits when treated with a prebiotic, probiotic or synbiotic therapy. These benefits include the improvement of their lipid profile, oxidative stress status, as well as the modulation of the inflammatory and immune responses. The associated benefits of prebiotic, probiotic or synbiotic functional foods have been studied, showing promising results into the prevention or control of diabetes and colorectal cancer. This novelty research provides new evidence that the use of functional foods along with medical therapy could be used to further enhance patient’s health

Tolerancia al frío en el cultivo del arroz en el mundo

El arroz (Oryza sativa L.) es una de las principales fuentes de alimentación para la población mundial y está sujeto a una demanda cada vez más difícil de cubrir (Khush, 1997; Cantrell y Reeves, 2002). Este cultivo es sensible a las bajas temperaturas y crece en regiones tropicales, subtropicales y templadas (Biswas et al., 2019). Se considera que el cultivo del arroz crece en condiciones óptimas entre los 25 y 35 °C y temperaturas mínimas críticas de crecimiento que varían según el estado de desarrollo (Biswas et al., 2019). Las bajas temperaturas son un importante factor limitante respecto a la productividad del cultivo y restringe su ubicación geográfica (Xin y Browse, 2001). Éste es un problema que afecta, principalmente, a regiones montañosas de los trópicos y regiones templadas (Xie et al., 2012). En el ámbito mundial, 15 millones de hectáreas en África, Asia, Australia, Europa y América del Sur y del Norte son afectadas por las bajas temperaturas cada año, lo que resulta en una pérdida de rendimiento anual de 1,0 a 3,9 t ha-1 (Jena y Hardy, 2012; Hyun et al., 2016). En Australia, la variación en los rendimientos promedio se debe en especial a eventos de temperatura inferiores a 15 °C durante la etapa reproductiva del cultivo, donde es común que las temperaturas sean tan bajas como a 11 o 12 °C (Reinke et al., 2012). En Bután, país ubicado al sur de la China y al norte de la India, el patrón de temperaturas es bajo-alto-bajo, como en Japón, el norte de China y Corea, donde la baja temperatura es un problema en la etapa temprana de crecimiento y también en la etapa reproductiva y de maduración. En Japón, 1,6 millones de hectáreas plantadas con arroz están expuestas a bajas temperaturas del verano. En Corea, donde se cultivan alrededor de un millón de hectáreas, los daños por frío pueden presentarse en la primavera y el otoño. En Nepal, 1,5 millones de hectáreas son amenazadas por bajas temperaturas. El clima frío recurrente con temperaturas de 8 a 10 °C (al inicio de la etapa vegetativa) hasta 13 a 15 °C (durante la floración y maduración) son las que afectan el arroz en Rusia. En California (U.S.A.), al igual que en Uruguay, el desafío relacionado con el clima es el vigor de las plántulas y la tolerancia al frío, tanto en estado vegetativo como en el reproductivo para ganar estabilidad en el rendimiento. En Chile, el país mas austral del mundo donde se cultiva el arroz (Donoso et al., 2014), tiene temperaturas mínimas inferiores a 10 °C durante la etapa vegetativa e inferiores a 15 °C, durante la etapa reproductiva (Donoso et al., 2015). En los distritos del norte de Bangladesh, el arroz se afecta por el frío durante el establecimiento y la etapa reproductiva del cultivo y la mortalidad de las plántulas puede llegar hasta el 90 %. Dos millones de hectáreas de arroz en el norte y el noreste de Bangladesh se han visto afectadas por una fuerte ola de frío que causa pérdidas parciales o totales del cultivo (Rashid y Yasmeen, 2018). Aumentar la producción de arroz en todo el mundo, incrementando la superficie sembrada es altamente improbable, pudiéndose generar un escenario de escasez alimentaria (Khush, 1997). Por ello, la sustentabilidad de la producción de arroz depende del desarrollo de nuevos cultivares de arroz, con rendimientos altos y estables, y tolerantes al frío, entre otros factores

Pseudo-Labeling Enhanced by Privileged Information and Its Application to In Situ Sequencing Images

Various strategies for label-scarce object detection have been explored by the computer vision research community. These strategies mainly rely on assumptions that are specific to natural images and not directly applicable to the biological and biomedical vision domains. For example, most semi-supervised learning strategies rely on a small set of labeled data as a confident source of ground truth. In many biological vision applications, however, the ground truth is unknown and indirect information might be available in the form of noisy estimations or orthogonal evidence. In this work, we frame a crucial problem in spatial transcriptomics - decoding barcodes from In-Situ-Sequencing (ISS) images - as a semi-supervised object detection (SSOD) problem. Our proposed framework incorporates additional available sources of information into a semi-supervised learning framework in the form of privileged information. The privileged information is incorporated into the teacher's pseudo-labeling in a teacher-student self-training iteration. Although the available privileged information could be data domain specific, we have introduced a general strategy of pseudo-labeling enhanced by privileged information (PLePI) and exemplified the concept using ISS images, as well on the COCO benchmark using extra evidence provided by CLIP.Comment: This paper has been accepted for publication at IJCAI 202

Inscrição votiva em língua lusitana (Arronches Portalegre)

Propõe-se leitura, interpretação e integração histórica da epígrafe redi- gida em língua lusitana, proveniente de uma herdade dos arredores de Arronches. Documenta o sacrifício de animais, designadamente de dez ovelhas, a divindades indígenas – Banda, Reva, Munis, Broeneia... – cujos nomes se fazem acompanhar de epítetos, um dos quais repetido com grafias diferentes (em dativo, Haracui, Aharacui, Harase), passí- vel de relacionar-se com o topónimo actual, Arronches. Na segunda parte, os três dedicantes, que poderão identificar-se como criadores de ovelhas, suplicam às divindades que lhes aceitem os sacrifícios. Considera-se muito viável a hipótese de relacionar esta e as outras epígrafes em língua lusitana – de Lamas de Moledo e Cabeço das Frá- guas – com as rotas da transumância logo nos primórdios da domina- ção romana

A Mathematical Model to Optimize the Neoadjuvant Chemotherapy Treatment Sequence for Triple-Negative Locally Advanced Breast Cancer

Background: Triple-negative locally advanced breast cancer is an aggressive tumor type. Currently, the standard sequence treatment is applied, administering anthracyclines first and then a taxane plus platinum. Clinical studies for all possible treatment combinations are not practical or affordable, but mathematical modeling of the active mitotic cell population is possible. Our study aims to show the regions with the tumor’s most substantial cellular population variation by utilizing all possible values of the parameters () that define the annihilatory drug capacity according to the proposed treatment. Method: A piecewise linear mathematical model was used to analyze the cell population growth by applying four treatments: standard sequences of 21 days (SS21) and 14 days (SS14), administering anthracyclines first, followed by a taxane plus platinum, and inverted sequences of 21 days (IS21) and 14 days (IS14), administering a taxane plus platinum first then anthracyclines. Results: The simulation showed a higher effect of IS14 over SS14 when the rate of drug resistance was larger in the cell population during DNA synthesis (G1 and S) compared to cells in mitosis (G2 and M). However, if the proportion of resistant cells in both populations was equivalent, then treatments did not differ. Conclusions: When resistance is considerable, IS14 is more efficient than SS14, reducing the tumor population to a minimum

Closure of a large lumbosacral myelomeningocele post operative defect with a human cadaveric split-thickness skin graft: a case report

Spina bifida is the most common birth defect of the central nervous system that is compatible with life, and myelomeningocele represents its most frequent form. Congenital myelomeningocele (CMM) has a worldwide incidence of 0.5 to 0.8 per 1,000 live newborns. CMM is a complex condition resulting from incomplete closure of the neural tube, mainly in the lumbosacral region. The objective of the surgical repair of the CMM is the reconstruction of all the tissue layers of the defect, avoiding possible postoperative complications. The aim of this case review is to present a re-epithelialization closure in a patient with a large CMM defect in who primary hermetic closure was not possible because there was too much tension at the edges of the defect. Therefore, human cadaveric split-thickness skin grafts were placed over the dura mater and the aponeurotic layer, covering the entire defect and an adequate healing and completely closure of the defect were observed in eight weeks. The surgical management of large meningomyelocele defects represents a major challenge and no single protocol exists for its reconstruction. The repair of an MMC defect should be performed during the first 72 hours after birth. After neurosurgical closure of the neural tube and dura, the myelomeningocele defect requires good quality skin and subcutaneous tissue with minimal wound tension for stable coverage. Human cadaveric skin grafts are considered a useful technique for temporary wound coverage because they lead to a more natural healing environment, possess ideal properties, and provide a physiological barrier that reduces microbiological contamination, in addition, it acts as a bridge to adhere to and to seal wound beds

Características de programas de atividade física na atenção básica de saúde do Brasil

The aim of this study was to describe the characteristics of programs that promote physical activity in the public primary care system by region of Brazil, subject to the presence or absence of multidisciplinary primary care teams (NASF). We conducted a cross sectional and population-based telephone survey of the health unit coordinators from 1,251 health care units. Coordinators were asked about the presence and characteristics of physical activity programs. Four out of ten health units reported having a physical activity intervention program, the most common involving walking groups. Most of the activities were performed in the morning, once or twice a week, and in sessions of 30 minutes or more. Physical education professionals were primarily responsible for directing the activities. Interventions occurred in the health unit itself or in adjacent community spaces. In general, these characteristics were similar between units with or without NASF, but varied substantially across regions. These findings will guide future physical activity policies and programs within primary care in Brazil.El objetivo fue describir las características de los programas de actividad física en atención primaria, de acuerdo con el Centro de Apoyo a la Salud de la Familia (NASF) y las regiones de Brasil. Se realizó una encuesta transversal telefónica con 1.251 coordinadores de las unidades de salud. Se preguntó a los coordinadores acerca de la presencia y características de intervenciones de actividad física en funcionamiento. Cuatro de cada diez centros de salud reportaron tener una intervención de actividad física, especialmente, grupos de paseo. La mayor parte de las actividades se llevan a cabo por la mañana una vez o dos veces por semana con sesiones de 30 minutos o más. Los profesores de educación física son los principales responsables de la supervisión de las actividades. Los programas se llevan a cabo en la clínica o en otros espacios públicos. Estas características fueron similares en unidades con o sin NASF y mostraron una variación regional en su prevalencia. Estas características permitirán enfocar próximas acciones para promover la actividad física dentro de la atención primaria de salud.O objetivo foi descrever as características dos programas de atividade física na atenção básica de saúde de acordo com a presença de Núcleo de Apoio à Saúde da Família (NASF) no município e por regiões do Brasil. Foi realizado um estudo transversal por inquérito telefônico com 1.251 coordenadores de unidades de saúde. Foi aplicado um questionário sobre presença de intervenções com atividade física e suas características de funcionamento. Quatro em cada dez unidades de saúde relataram ter uma intervenção com atividade física, especialmente grupos de caminhada. A maior parte da atividade é realizada na manhã uma vez ou duas vezes por semana, com sessões de 30 minutos ou mais. Profissionais de educação física são os principais responsáveis por supervisionar as atividades. Os programas ocorrem na unidade de saúde ou outros espaços comunitários. Estas características, de modo geral, foram semelhantes entre unidades com ou sem NASF no município e apresentaram variação entre as regiões. Os resultados desse estudo irão permitir melhor direcionamento das próximas ações de promoção de atividade física na atenção básica de saúde.Universidade Federal de São Carlos Departamento de GerontologiaUniversidade Estadual Paulista Núcleo de Atividade Física, Esporte e SaúdeUniversidade Federal de Pelotas Grupo de Estudos em Epidemiologia da Atividade FísicaUniversidade Federal de São Paulo (UNIFESP)Centers for Disease Control and Prevention National Center for Chronic Disease Prevention and Health PromotionWashington University in St. Louis George Warren Brown School of Social WorkUniversidade de São Paulo Escola de Artes, Ciências e HumanidadesHospital Israelita Albert EinsteinMinistério da SaúdeEmory University Rollins School of Public HealthUNIFESPSciEL

High-velocity collimated outflows in planetary nebulae: NGC 6337, He 2-186, and K 4-47

We have obtained narrow-band images and high-resolution spectra of the planetary nebulae NGC 6337, He 2-186, and K 4-47, with the aim of investigating the relation between their main morphological components and several low-ionization features present in these nebulae. The data suggest that NGC 6337 is a bipolar PN seen almost pole on, with polar velocities higher than 200 km/s. The bright inner ring of the nebula is interpreted to be the "equatorial" density enhancement. It contains a number of low-ionization knots and outward tails that we ascribe to dynamical instabilities leading to fragmentation of the ring or transient density enhancements due to the interaction of the ionization front with previous density fluctuations in the ISM. The lobes show a pronounced point-symmetric morphology and two peculiar low-ionization filaments whose nature remains unclear. The most notable characteristic of He 2-186 is the presence of two high-velocity (higher than 135 km/s) knots from which an S-shaped lane of emission departs toward the central star. K 4-47 is composed of a compact core and two high-velocity, low-ionization blobs. We interpret the substantial broadening of line emission from the blobs as a signature of bow shocks, and using the modeling of Hartigan, Raymond, & Hartman (1987), we derive a shock velocity of 150 km/s and a mild inclination of the outflow on the plane of the sky. We discuss possible scenarios for the formation of these nebulae and their low-ionization features. In particular, the morphology of K 4-47 hardly fits into any of the usually adopted mass-loss geometries for single AGB stars. Finally, we discuss the possibility that point-symmetric morphologies in the lobes of NGC 6337 and the knots of He 2-186 are the result of precessing outflows from the central stars.Comment: 16 pages plus 7 figures, ApJ accepted. Also available at http://www.iac.es/publicaciones/preprints.htm