Overexpression of Forkhead Box Protein M1 (FOXM1) in Ovarian Cancer Correlates with Poor Patient Survival and Contributes to Paclitaxel Resistance

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Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system

Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis

Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment

Development of a LAMP assay for detection of Leishmania infantum infection in dogs using conjunctival swab samples

Background: Leishmania infantum infections in dogs play a crucial role in the transmission of pathogens causing visceral leishmaniasis to humans in the Gansu province, northwest China. To be able to control zoonotic transmission of the parasite to humans, a non-invasive loop-mediated isothermal amplification (LAMP) assay to specifically detect L. infantum infections in dogs was developed. Methods: The primers used in the LAMP assay were designed to target kinetoplast DNA minicircle sequences of the L. infantum isolate MCAN/CN/90/SC and tested using DNA isolated from promastigotes of different Leishmania species. The LAMP assay was evaluated with conjunctional swab samples obtained from 111 and 33 dogs living in an endemic and a non-endemic region of zoonotic visceral leishmaniasis in the Gansu province, respectively. The LAMP assay was also compared with conventional PCR, ELISA and microscopy using conjunctional swab, serum and bone marrow samples from the dogs, respectively. Results: The LAMP assay detected 1 fg of L. infantum DNA purified from cultured promastigotes which was 10-fold more sensitive than a conventional PCR test using Leishmania genus-specific primers. No cross reaction was observed with DNA isolated from promastigotes of L. donovani, L. major, L. tropica, and L. braziliensis, and the L. infantum reference strain MHOM/TN/80/IPT1. The L. infantum-positive rates obtained for field-collected samples were 61.3%, 58.6%, 40.5% and 10.8% by LAMP, PCR, ELISA and microscopy, respectively. As only one out of the 33 samples from control dogs from the non-endemic region of zoonotic visceral leishmaniasis was positive by the LAMP assay and the PCR test, the observed true negative rate (specificity) was 97% for both methods. Conclusion: This study has shown that the non-invasive, conjunctional swab-based LAMP assay developed was more sensitive in the detection of leishmaniasis in dogs than PCR, ELISA and microscopy. The findings indicate that the LAMP assay is a sensitive and specific method for the field surveillance of domestic dogs, particularly of asymptomatic canines, in ZVL-endemic areas in western China

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4^{+} and CD8^{+} T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1^{+}, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8^{+}CD45RA^{+}CD27^{-} T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis

Atenção ao idoso na estratégia de Saúde da Família: atuação do enfermeiro

Este estudo objetivou descrever a consulta de enfermagem ao idoso realizada na ESF; identificar possíveis dificuldades na atenção à saúde do idoso, bem como os cursos de qualificação profissional realizados e as necessidades de aprendizagem. Os dados foram coletados por meio da entrevista semiestruturada e submetidos à análise descritiva e temática. Foram entrevistadas 12 enfermeiras, a maioria estando na faixa etária de anos de formada (41%) em instituição particular (75%). Emergiram duas categorias temáticas: consulta de enfermagem ao idoso na ESF e qualificação profissional para a atenção à saúde do idoso. Foi considerado como desafio na realização da consulta de enfermagem a obtenção de dados fidedignos, a resolutividade e o apoio familiar. Os cursos para qualificar a atenção ao idoso ocorreram durante o período de graduação, destacando a falta de oportunidade, a pouca oferta e a necessidade de se aprofundar sobre o processo de envelhecimento.Este estudio tuvo como objetivo describir la consulta de enfermería realizada por el anciano en la ESF; identificar posibles dificultades en la atención a la salud del anciano, así como los cursos de calificación profesional realizados y las necesidades de aprendizaje. Los datos fueron recogidos a través de la entrevista semiestructurada y sometidos al análisis descriptivo temático. Fueron entrevistadas doce enfermeras, estando la mayoría situadas en la faja etaria de 23 a 28 años (66%), con 1-2 años de graduadas (41%) en instituciones particulares (75%). Emergieron dos categorías temáticas: consulta de enfermería del anciano en la ESF y calificación profesional para la atención de la salud del anciano. Fue considerado como desafío en la realización de la consulta de enfermería la obtención de datos fidedignos, la resolutividad y el apoyo familiar. Los cursos para calificar la atención al anciano, tuvieron lugar durante el período de graduación, destacándose la falta de oportunidad, la poca oferta y la necesidad de profundizar sobre el proceso de envejecimiento.This study aimed to describe the nursing consultation for the elderly provided at the Family Health Strategy (ESF, acronym in Portuguese); identify possible difficulties in delivering health care to the elderly, as well as the professional qualification courses performed and the learning needs. Data were collected through semi-structured interviews and submitted to descriptive and thematic analysis. Interviews were performed with 12 nurses, most with ages between years since graduation (41%) in private institutions (75%). Two thematic categories emerged from the analysis: nursing consultation for the elderly performed at ESF and professional qualification in health care for the elderly. Obtaining reliable data in the nursing consultation, resolution and family support were considered as challenges. The courses to qualify professionals for elderly care occurred during their graduation course, highlighting the lack of opportunity, the short supply and the need for deeper studies about the aging process

Isokinetic muscle function comparison of lower limbs among elderly fallers and non-fallers

O objetivo deste estudo foi identificar se há diferenças entre o desempenho muscular de tornozelo, joelho e quadril em idosos com e sem relato de queda nos últimos seis meses. Foram incluídos 81 idosos com 65 anos ou mais: 56 negaram quedas (G1) e 25 relataram quedas (G2). Utilizou-se o questionário perfil de atividade humana para medir o nível de atividade física, e o dinamômetro isocinético para mensurar os parâmetros físicos da função muscular. Os grupos não diferiram entre si em relação à idade (p=0,925), duração (p=0,065) e frequência (p=0,302) da prática do exercício físico, índice de massa corpórea (p=0,995) e nível de atividade física (p=0,561). O G2 apresentou menor desempenho para as variáveis pico de torque de flexão e extensão de joelho esquerdo (p=0,027 e p=0,030, respectivamente) e trabalho por peso corporal (p=0,040) de flexão de joelho esquerdo a 60°/s; pico de torque e trabalho por peso corporal de flexão e extensão de joelho a 180°/s bilateralmente (p<0,050); e potência média de flexão de joelhos direito e esquerdo (p=0,030). A maioria das variáveis do tornozelo e quadril não apresentou diferenças entre os grupos. Apenas a variável pico de torque de extensão de quadril esquerdo foi significativamente maior no G1 (p=0,035). É importante considerar a função muscular do joelho na avaliação clínica de idosos para direcionar a intervenção terapêutica e a prevenção de quedas.The aim of this study was to identify whether there are differences between the performance of muscular groups of ankle, knee and hip among elderly people who didn't have falls and individuals who reported falls in the last six months. The study included 81 elderly aged 65 or older: 56 non-faller subjects (G1) and 25 faaller subjects (G2). To obtain the level of physical activity, the questionnaire Human Activity Profile was used, and the muscle function of the lower limbs was assessed using isokinetic dynamometer. The groups did not differ regarding age (p=0.925), duration (p=0.065) and frequency (p=0.302) of the practice of physical exercise, body mass index (BMI) (p=0.995) and level of physical activity (p=0.561). The G2 showed a lower performance of peak torque of left knee flexion and extension (p=0.027 and p=0.030, respectively) and work proportional to body weight (p=0.040) of left knee flexion at 60°/s; peak torque and work proportional to body weight of bilaterally knee flexion and extension at 180°/s (p<0.05) and average power of right and left knee extension (p=0.03). Most variables of ankle and hip joints did not differ between groups. Only peak torque of left hip extension was significantly higher in the non-faller group (p=0.035). It is important to consider knee muscle function in the clinical evaluation of elderly in order to make the intervention more assertive and thus to prevent falls

Evaluative and discriminative properties of the Portuguese MacNew Heart Disease Health‐related Quality of Life Questionnaire.

Qual Life Res. 2005 Dec;14(10):2335-41. Evaluative and discriminative properties of the Portuguese MacNew Heart Disease Health-related Quality of Life Questionnaire. Leal A, Paiva C, Höfer S, Amado J, Gomes L, Oldridge N. Cardiac Rehabilitation Unit, Hospital Sto António Porto, Largo Prof Abel Salazar 400, Portugal. [email protected] Abstract The aim of this study was to validate the Portuguese version of the self-administered MacNew Heart Disease Health-related Quality of Life (MacNew) questionnaire in patients after diagnosis of acute coronary syndrome. The MacNew, with a Global score and physical, emotional and social subscales, the Short Form SF-36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline by 150 patients and again by 48 clinically stable patients 2-3 weeks later. A cohort of 50 different patients completed the same questionnaires before and after a cardiac rehabilitation program in order to examine responsiveness. Acceptance of the MacNew by the patients was good and the three factor model was substantiated and explained 52.2% of the variance. Internal consistency, intra-class-correlation, and test-retest reliability each exceeded 0.72. The predicted construct validity hypotheses were partially confirmed. The discriminative validity of the MacNew was confirmed with significantly higher MacNew scores for patients with normal left ventricular function, with improved health status, and who were not anxious or depressed. Even though MacNew scores improved significantly following cardiac rehabilitation, the evaluative validity of the MacNew was less robust with small responsiveness statistics. The Portuguese version of the MacNew HRQL questionnaire appears to be a reliable, valid, and moderately responsive instrument to evaluate health-related quality of life after diagnosis of acute coronary syndrome. PMID: 16328913 [PubMed - indexed for MEDLINE