Evidence map of diagnosis, treatment, prognosis, prevention, and control in visceral leishmaniasis.

Objective: To develop an evidence map on visceral leishmaniasis prevention, control, diagnosis, treatment, and prognosis. Methods: Systematic reviews on visceral leishmaniasis were searched using MEDLINE/PubMed and Virtual Health Library. After selection, each included systematic review was assessed, characterized, and categorized by intervention type and by outcomes, according to the methodology offered by the PAHO/WHO Latin American and Caribbean Center on Health Sciences Information (BIREME). The methodological quality was assessed using the AMSTAR2 tool to determine the confidence level of the evidence obtained. Results: Among the prevention and control interventions, insecticide spraying, bednets, dog collars, and dog culling were the most assessed, emphasizing that insecticidal dog collars can reduce visceral leishmaniasis incidence in dogs. Regarding diagnosis, polymerase chain reaction (PCR), rK39 immunochromatographic test (rK39 ICT), and direct agglutination test (DAT) presented high sensitivity and specificity. As for treatment, pentavalent antimonials and amphotericin B were the most analyzed drugs and showed therapeutic success; however, serious adverse events can occur due to their use. The prognostic factors identified were anemia, edema, bleeding, jaundice, age, and HIV coinfection. Conclusions: The evidence map developed shows rK39 ICT and DAT as promising diagnostic alternatives and reinforces the efficacy of liposomal amphotericin B and pentavalent antimonials. Insecticide-impregnated dog collars appear as a promising measure for the control of visceral leishmaniasis, but there is also a need for future studies and reviews with higher methodological quality, especially on prevention and control interventions.

Valosin-containing protein VCP/p97 is essential for the intracellular development of Leishmania and its survival under heat stress.

Valosin-containing protein (VCP)/p97/Cdc48 is one of the best-characterised type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homologue (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, Leishmania infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive (ts) LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity. Interestingly, these VCP mutants are also unable to survive heat stress, and a ts VCP mutant is defective in amastigote growth. Consistent with LiVCP's essential function in amastigotes, LiVCP messenger ribonucleic acid undergoes 3'Untranslated Region (UTR)-mediated developmental regulation, resulting in higher VCP expression in amastigotes. Furthermore, we show that parasite mutant lines expressing lower VCP levels or dominant negative VCP forms exhibit high accumulation of polyubiquitinated proteins and increased sensitivity to proteotoxic stress, supporting the ubiquitin-selective chaperone function of LiVCP. Together, these results emphasise the crucial role LiVCP plays under heat stress and during the parasite intracellular development.

Sarcopenia and Skeletal Muscle Quality as Predictors of Postoperative Complication and Early Mortality in Gynecologic Cancer.

OBJECTIVE: This study aimed to evaluate the influence of sarcopenia and the indicators of skeletal muscle (SM) quality on surgical outcomes in women with ovarian and endometrial cancer who underwent oncologic surgery. METHODS: Endometrial and ovarian cancer patients admitted between 2008 and 2015 and who had computerized tomography images available within 45 days before surgery were enrolled in a retrospective cohort (n = 250). Computerized tomography images at the third lumbar vertebra were used to assess SM. Skeletal muscle index (SMI) was calculated in the range from -29 to +150 Hounsfield Units; reduced muscle attenuation (range, -29 to +29 HU) was classified as low-radiodensity skeletal muscle index (LRSMI). By subtracting the LRSMI area from total SMI, high-radiodensity skeletal muscle index (HRSMI) was created. Sarcopenia was defined when SMI was less than 38.9 cm/m. Multiple logistic regression evaluated predictors of surgical complications. RESULTS: Patients in lower HRSMI quartiles and in the highest quartiles of LRSMI had more postoperative surgical complication and had prolonged hospital stay. Both sarcopenia and the quality indicators of SM were predictors of increased risk of surgical complication, HRSMI being the strongest predictor. However, in a combined adjustment with sarcopenia, only HRSMI remained in the model as an independent predictor for surgical complication. In addition, HRSMI was the only indicator associated with early mortality (<30 days). CONCLUSIONS: The indicators of SM quality were the most significant predictors of surgical complications. Classifying muscle quality in terms of low-radiodensity or high-radiodensity area is a promising strategy to understand the impact of SM quality on unfavorable surgical outcomes in cancer patients.

No evidence for Fabaceae Gametophytic self-incompatibility being determined by Rosaceae, Solanaceae, and Plantaginaceae S-RNase lineage genes.

BACKGROUND: Fabaceae species are important in agronomy and livestock nourishment. They have a long breeding history, and most cultivars have lost self-incompatibility (SI), a genetic barrier to self-fertilization. Nevertheless, to improve legume crop breeding, crosses with wild SI relatives of the cultivated varieties are often performed. Therefore, it is fundamental to characterize Fabaceae SI system(s). We address the hypothesis of Fabaceae gametophytic (G)SI being RNase based, by recruiting the same S-RNase lineage gene of Rosaceae, Solanaceae or Plantaginaceae SI species. RESULTS: We first identify SSK1 like genes (described only in species having RNase based GSI), in the Trifolium pratense, Medicago truncatula, Cicer arietinum, Glycine max, and Lupinus angustifolius genomes. Then, we characterize the S-lineage T2-RNase genes in these genomes. In T. pratense, M. truncatula, and C. arietinum we identify S-RNase lineage genes that in phylogenetic analyses cluster with Pyrinae S-RNases. In M. truncatula and C. arietinum genomes, where large scaffolds are available, these sequences are surrounded by F-box genes that in phylogenetic analyses also cluster with S-pollen genes. In T. pratense the S-RNase lineage genes show, however, expression in tissues not involved in GSI. Moreover, levels of diversity are lower than those observed for other S-RNase genes. The M. truncatula and C. arietinum S-RNase and S-pollen like genes phylogenetically related to Pyrinae S-genes, are also expressed in tissues other than those involved in GSI. To address if other T2-RNases could be determining Fabaceae GSI, here we obtained a style with stigma transcriptome of Cytisus striatus, a species that shows significant difference on the percentage of pollen growth in self and cross-pollinations. Expression and polymorphism analyses of the C. striatus S-RNase like genes revealed that none of these genes, is the S-pistil gene. CONCLUSION: We find no evidence for Fabaceae GSI being determined by Rosaceae, Solanaceae, and Plantaginaceae S-RNase lineage genes. There is no evidence that T2-RNase lineage genes could be determining GSI in C. striatus. Therefore, to characterize the Fabaceae S-pistil gene(s), expression analyses, levels of diversity, and segregation analyses in controlled crosses are needed for those genes showing high expression levels in the tissues where GSI occurs.

Validity of a Smartphone-Based Fall Detection Application on Different Phones Worn on a Belt or in a Trouser Pocket.

The objective of this study was to evaluate the sensitivity and specificity of a smartphone-based fall detection application when different smartphone models are worn on a belt or in a trouser pocket. Eight healthy adults aged between 18 and 24 years old simulated 10 different types of true falls, 5 different types of falls with recovery, and 11 daily activities, five consecutive times. Participants wore one smartphone in a pocket that was attached to their belt and another one in their trouser pocket. All smartphones were equipped with a built-in accelerometer and the fall detection application. Four participants tested the application on a Samsung S3 and four tested the application on a Samsung S3 mini. Sensitivity scores were .75 (Samsung S3 belt), .88 (Samsung S3 mini trouser pocket), and .90 (Samsung S3 mini belt/Samsung S3 trouser pocket). Specificity scores were .87 (Samsung S3 trouser pocket), .91 (Samsung S3 mini trouser pocket), .97 (Samsung S3 belt), and .99 (Samsung S3 mini belt). These results suggest that an application on a smartphone can generate valid fall alarms when worn on a belt or in a trouser pocket. However, sensitivity should be improved before implementation of the application in practice.

Patterns of evolution at the gametophytic self-incompatibility Sorbus aucuparia (Pyrinae) S pollen genes support the non-self recognition by multiple factors model.

S-RNase-based gametophytic self-incompatibility evolved once before the split of the Asteridae and Rosidae. In Prunus (tribe Amygdaloideae of Rosaceae), the self-incompatibility S-pollen is a single F-box gene that presents the expected evolutionary signatures. In Malus and Pyrus (subtribe Pyrinae of Rosaceae), however, clusters of F-box genes (called SFBBs) have been described that are expressed in pollen only and are linked to the S-RNase gene. Although polymorphic, SFBB genes present levels of diversity lower than those of the S-RNase gene. They have been suggested as putative S-pollen genes, in a system of non-self recognition by multiple factors. Subsets of allelic products of the different SFBB genes interact with non-self S-RNases, marking them for degradation, and allowing compatible pollinations. This study performed a detailed characterization of SFBB genes in Sorbus aucuparia (Pyrinae) to address three predictions of the non-self recognition by multiple factors model. As predicted, the number of SFBB genes was large to account for the many S-RNase specificities. Secondly, like the S-RNase gene, the SFBB genes were old. Thirdly, amino acids under positive selection-those that could be involved in specificity determination-were identified when intra-haplotype SFBB genes were analysed using codon models. Overall, the findings reported here support the non-self recognition by multiple factors model.

Profile of hospital admissions and deaths due to severe acute respiratory syndrome caused by COVID-19 in Piauí, Brazil: a descriptive study, 2020-2021. / Perfil de internações e óbitos hospitalares por síndrome respiratória aguda grave causada por COVID-19 no Piauí: estudo descritivo, 2020-2021.

OBJECTIVE: To describe the profile and temporal variation of hospital admissions and deaths due to severe acute respiratory syndrome (SARS) caused by COVID-19 in Piauí, Brazil, according to place of hospitalization. METHODS: We performed a descriptive study using data from the Influenza Surveillance Information System between 2020 and 2021. Case fatality ratio among hospital records with outcome and respective 95% confidence intervals (95%CI) were calculated. RESULTS: We included 12,649 individuals who were mostly male (57.1%), Black (61.2%) and had one or two comorbidities (30.5%). Case fatality ratio among hospital records with outcome was higher in the state's interior region than in its capital, with proportion of 44.1% (95%CI 42.0;46.3) for those who were hospitalized, 82.3% (95%CI 79.7;84.8) for those admitted to intensive care units and 96.6% (95%CI 94.9;97.8) for those undergoing invasive mechanical ventilation. CONCLUSION: The study enabled characterization of the profile of SARS hospitalizations due to COVID-19 in Piauí and demonstrated high case fatality ratio, among hospital records with outcome, which remained high during the study period, especially in the interior of the state.

[Epidemiological profile and time trend in visceral leishmaniasis: Piauí, Brazil, 2008-2018]. / Perfil epidemiológico e tendência temporal da leishmaniose visceral: Piauí, Brasil, 2008 a 2018.

Visceral leishmaniasis (VL) or kala azar is one of the main neglected tropical diseases, of major importance due to the lethal nature of this zoonosis caused by protozoa of genus Leishmania. The study aimed to analyze the time trend in VL cases in the state of Piauí, Brazil, from 2008 to 2018, within the total period from 1971 to 2018. Data were obtained from the Brazilian Information System for Notificable Diseases (SINAN) and the Brazilian Mortality Information System (SIM). For burden of disease analysis, data were collected from the Institute for Health Metrics and Evaluation through the Global Burden of Diseases, Injuries, and Risk Factors (GBD Compare). Prais-Winsten regression analysis was used. A total of 2,374 cases were recorded with probable infection in the state of Piauí and 2,492 cases in residents of the state. The historical series analyzed, from 1971 to 2018, reaffirms the cyclical nature of the disease, based on the identification of epidemic peaks in 1983-1984, 1993-1994, 2003-2004, and 2013-2014. No significant alterations were identified in the trends in incidence, mortality, and case-fatality coefficients in the state. However, there was a significant increase in the incidence coefficient in the Chapada das Mangabeiras Development Territory, with an annual percent change of 17.5%, and a decrease in the Vale do Sambito Development Territory (-18.3%) and Vale do Rio Guaribas Development Territory (-8,1%). VL has a high burden of disease, measured by disability-adjusted life years, and is among the leading neglected tropical diseases in the state of Piauí. The study concludes by recommending the improvement of surveillance and control measures for this disease.

A leishmaniose visceral (LV) ou calazar é uma das principais doenças tropicais negligenciadas, de grande importância devido ao caráter letal desta zoonose causada por protozoários do gênero Leishmania. Objetivou-se analisar a tendência temporal dos casos de LV no Estado do Piauí, Brasil, de 2008 a 2018, inserindo-o dentro do período total de 1971 a 2018. Utilizaram-se dados do Sistema de Informação de Agravos de Notificação (SINAN) e do Sistema de Informações sobre Mortalidade (SIM). Para análise da carga da doença, foram coletados dados do Instituto de Métricas e Avaliação em Saúde através do estudo Carga Global de Doenças, Lesões e Fatores de Risco. Foi empregada a análise de regressão Prais-Winsten. Foram registrados 2.374 casos com provável local de infecção no Piauí e 2.492 casos em residentes do estado. A série histórica analisada, de 1971 a 2018, reafirma o caráter cíclico da doença, pela presença dos picos epidêmicos identificados em 1983 e 1984, 1993 e 1994, 2003 e 2004 e 2013 e 2014. Não foram identificadas alterações significativas na tendência dos coeficientes de incidência, mortalidade e letalidade no estado. No entanto, houve aumento significativo do coeficiente de incidência no Território de Desenvolvimento (TD) Chapada das Mangabeiras (variação percentual anual de 17,5%) e redução no TD Vale do Sambito (-18,3%) e TD Vale do Rio Guaribas (-8,1%). A LV tem a maior carga de doença medida em anos de vida ajustados por deficiência entre as doenças tropicais negligenciadas do estado. Recomenda-se o aprimoramento das medidas de vigilância e controle do agravo.

La leishmaniasis visceral (LV) o kala azar es una de las principales enfermedades tropicales desatendidas de gran importancia, debido al carácter letal de esta zoonosis causada por protozoos del género Leishmania. El objetivo fue analizar la tendencia temporal de los casos de LV en el estado de Piauí, Brasil, de 2008 a 2018, incluyéndola dentro del período total de 1971 a 2018. Se utilizaron datos del Sistema Brasileño de Información de Enfermedades de Notificación (SINAN) y del Sistema de Información sobre Mortalidad (SIM). Para el análisis de la carga de la enfermedad, se recogieron datos del Instituto de Métricas y Evaluación en Salud, a través del estudio Carga Global de Enfermedades, Lesiones y Factores de Riesgo (GBD Compare). Se empleó el análisis de regresión Prais-Winsten. Se registraron 2.374 casos con probable lugar de infección en Piauí y 2492 casos en residentes del estado. La serie histórica analizada, de 1971-2018, reafirma el carácter cíclico de la enfermedad por la presencia de los picos epidémicos, identificados en 1983 y 1984, 1993 y 1994, 2003 y 2004 y 2013 y 2014. No se identificaron alteraciones significativas en la tendencia de los coeficientes de incidencia, mortalidad y letalidad en el estado. No obstante, hubo un aumento significativo del coeficiente de incidencia en el Territorio de Desarrollo (TD) Chapada das Mangabeiras (variación del porcentaje anual de 17,5%) y reducción en el TD Vale do Sambito (-18,3%) y TD Vale do Rio Guaribas (-8,1%). La LV tiene una mayor carga de enfermedad medida en años de vida ajustados por deficiencia entre las enfermedades tropicales olvidadas del estado. Se recomienda el perfeccionamiento de las medidas de vigilancia y control de la enfermedad.

Evolutionary patterns at the RNase based gametophytic self - incompatibility system in two divergent Rosaceae groups (Maloideae and Prunus).

BACKGROUND: Within Rosaceae, the RNase based gametophytic self-incompatibility (GSI) system has been studied at the molecular level in Maloideae and Prunus species that have been diverging for, at least, 32 million years. In order to understand RNase based GSI evolution within this family, comparative studies must be performed, using similar methodologies. RESULT: It is here shown that many features are shared between the two species groups such as levels of recombination at the S-RNase (the S-pistil component) gene, and the rate at which new specificities arise. Nevertheless, important differences are found regarding the number of ancestral lineages and the degree of specificity sharing between closely related species. In Maloideae, about 17% of the amino acid positions at the S-RNase protein are found to be positively selected, and they occupy about 30% of the exposed protein surface. Positively selected amino acid sites are shown to be located on either side of the active site cleft, an observation that is compatible with current models of specificity determination. At positively selected amino acid sites, non-conservative changes are almost as frequent as conservative changes. There is no evidence that at these sites the most drastic amino acid changes may be more strongly selected. CONCLUSIONS: Many similarities are found between the GSI system of Prunus and Maloideae that are compatible with the single origin hypothesis for RNase based GSI. The presence of common features such as the location of positively selected amino acid sites and lysine residues that may be important for ubiquitylation, raise a number of issues that, in principle, can be experimentally addressed in Maloideae. Nevertheless, there are also many important differences between the two Rosaceae GSI systems. How such features changed during evolution remains a puzzling issue.

The AAA + ATPase valosin-containing protein (VCP)/p97/Cdc48 interaction network in Leishmania.

Valosin-containing protein (VCP)/p97/Cdc48 is an AAA + ATPase associated with many ubiquitin-dependent cellular pathways that are central to protein quality control. VCP binds various cofactors, which determine pathway selectivity and substrate processing. Here, we used co-immunoprecipitation and mass spectrometry studies coupled to in silico analyses to identify the Leishmania infantum VCP (LiVCP) interactome and to predict molecular interactions between LiVCP and its major cofactors. Our data support a largely conserved VCP protein network in Leishmania including known but also novel interaction partners. Network proteomics analysis confirmed LiVCP-cofactor interactions and provided novel insights into cofactor-specific partners and the diversity of LiVCP complexes, including the well-characterized VCP-UFD1-NPL4 complex. Gene Ontology analysis coupled with digitonin fractionation and immunofluorescence studies support cofactor subcellular compartmentalization with either cytoplasmic or organellar or vacuolar localization. Furthermore, in silico models based on 3D homology modeling and protein-protein docking indicated that the conserved binding modules of LiVCP cofactors, except for NPL4, interact with specific binding sites in the hexameric LiVCP protein, similarly to their eukaryotic orthologs. Altogether, these results allowed us to build the first VCP protein interaction network in parasitic protozoa through the identification of known and novel interacting partners potentially associated with distinct VCP complexes.

Inferences on specificity recognition at the Malus×domestica gametophytic self-incompatibility system.

In Malus × domestica (Rosaceae) the product of each SFBB gene (the pollen component of the gametophytic self-incompatibility (GSI) system) of a S-haplotype (the combination of pistil and pollen genes that are linked) interacts with a sub-set of non-self S-RNases (the pistil component), but not with the self S-RNase. To understand how the Malus GSI system works, we identified 24 SFBB genes expressed in anthers, and determined their gene sequence in nine M. domestica cultivars. Expression of these SFBBs was not detected in the petal, sepal, filament, receptacle, style, stigma, ovary or young leaf. For all SFBBs (except SFBB15), identical sequences were obtained only in cultivars having the same S-RNase. Linkage with a particular S-RNase was further established using the progeny of three crosses. Such data is needed to understand how other genes not involved in GSI are affected by the S-locus region. To classify SFBBs specificity, the amino acids under positive selection obtained when performing intra-haplotypic analyses were used. Using this information and the previously identified S-RNase positively selected amino acid sites, inferences are made on the S-RNase amino acid properties (hydrophobicity, aromatic, aliphatic, polarity, and size), at these positions, that are critical features for GSI specificity determination.

Perfil clínico-epidemiológico e desfecho de pessoas idosas hospitalizadas por COVID-19 / Clinical-epidemiological profile and outcome of old people hospitalized for COVID-19

Objetivo: Descrever o perfil clínico-epidemiológico e desfecho de pessoas idosas hospitalizados por COVID-19 no Hospital Universitário do Piauí. Métodos: Realizou-se um estudo observacional, transversal, realizado com dados secundários envolvendo 137 prontuários de pacientes idosos internados por COVID-19 no HU durante o período de abril a dezembro de 2020. Os dados foram coletados nos meses de agosto e setembro de 2021. Utilizou-se um formulário formado por questões equivalentes aos dados sociodemográficos e epidemiológicos dos pacientes idosos. Os dados foram analisados utilizando o Software estatístico SPSS versão 25. Resultados Observou-se que o "uso de ventilação mecânica" (Odds Ratio: 35,96 [10,23-126,47]) e "tipo de leito de internação" (Odds Ratio: 9,40 [2,69-32,82]) foram as variáveis que melhor explicam os óbitos sendo preditoras independentes para esse desfecho. Houve associação estatisticamente significativa entre a quantidade de comorbidades (p=0,007), a presença de manifestações clínicas (p=0,003), a quantidade de manifestações clínicas (p=0,003) e óbito. O menor tempo de sobrevida foi associado à internação em UTI e uso de ventilação mecânica (p=0,000). Conclusão: Os resultados do estudo evidenciam que a presença de fatores de risco para a COVID-19, manifestações clínicas da doença, estavam internados em leitos de UTI, em uso de VM e os que apresentavam idade superior tiveram piores desfechos. Descritores: Perfil de saúde; Saúde do idoso; Coronavirus. COVID-19.

Objective: To describe the clinical-epidemiological profile and outcome of old people hospitalized for COVID-19 at the University Hospital of Piauí. Methods:An observational, cross-sectional study was carried out with secondary data involving 137 medical records of old patients hospitalized for COVID-19 in the UH during the period from April to December 2020. Data were collected in August and September 2021. Aform consisting of questions equivalent to the sociodemographic and epidemiological data of old patients was used. Data were analyzed using SPSS statistical software version 25. Results: It was observed that the "use of mechanical ventilation" (Odds Ratio: 35.96 [10.23-126.47]) and "type of hospitalization bed" (Odds Ratio: 9.40 [2.69-32.82]) were the variables that best explain the deaths being independent predictors for this outcome. There was a statistically significant association between the number of comorbidities (p=0.007), the presence of clinical manifestations (p=0.003), the number of clinical manifestations (p=0.003) and death. The shorter survival time was associated with ICU admission and use of mechanical ventilation (p=0.000). Conclusion: The results of the study show that the presence of risk factors for COVID-19, clinical manifestations of the disease, to be admitted to ICU beds, using MV and those who were older had worse outcomes. Descriptors: Health profile; Health of old people; Coronavirus. COVID-19.

Seizure impact on the school attendance in children with epilepsy.

RATIONALE: Epilepsy has a significant influence on the patient's quality of life. The objective of this study was to evaluate the impact of ongoing seizures on school attendance amongst children with epilepsy. METHODS: This was a prospective study, conducted at the University of Campinas, in the pediatric epilepsy clinic, from January 2005 to August 2006. We enrolled 50 consecutive children who had a diagnosis of epilepsy. Parents were interviewed by one of the authors using a semi-structured questionnaire that included questions specifically addressing the impact of epilepsy on the child's academic life. RESULTS: Fifty patients were evaluated, 34 boys and 16 girls; ages ranged from 6 to 18 years old (mean=11). Eighty-eight percent of patients in the study missed at least 1 day of school due to seizures. The reason given by parents for a school absence was seizure in 75%, medical appointment in 79.5%, epilepsy related tests (EEG, MRI, etc.) in 68.2%, and other in 0.03%. Almost half of the parents (46%) believed that if the child had a seizure at school he/she should leave school immediately. Sixty percent of families allowed the child to skip a school day even if there was no illness and the child had no seizures on that day. Among those patients with siblings, 12.5% had a brother or sister who was absent from school for at least 1 day due to his/her sibling's epilepsy. CONCLUSION: Seizures have a significant impact on school attendance, and as a result may increase the academic difficulties faced by children with epilepsy. This effect may be especially pronounced in children with symptomatic epilepsy and medically intractable seizures.

Evidence map of diagnosis, treatment, prognosis, prevention, and control in visceral leishmaniasis / Mapa de evidencia sobre el diagnóstico, tratamiento, pronóstico, prevención y control de la leishmaniasis visceral / Mapa de evidências de diagnóstico, tratamento, prognóstico, prevenção e controle da leishmaniose visceral

ABSTRACT Objective. To develop an evidence map on visceral leishmaniasis prevention, control, diagnosis, treatment, and prognosis. Methods. Systematic reviews on visceral leishmaniasis were searched using MEDLINE/PubMed and Virtual Health Library. After selection, each included systematic review was assessed, characterized, and categorized by intervention type and by outcomes, according to the methodology offered by the PAHO/WHO Latin American and Caribbean Center on Health Sciences Information (BIREME). The methodological quality was assessed using the AMSTAR2 tool to determine the confidence level of the evidence obtained. Results. Among the prevention and control interventions, insecticide spraying, bednets, dog collars, and dog culling were the most assessed, emphasizing that insecticidal dog collars can reduce visceral leishmaniasis incidence in dogs. Regarding diagnosis, polymerase chain reaction (PCR), rK39 immunochromatographic test (rK39 ICT), and direct agglutination test (DAT) presented high sensitivity and specificity. As for treatment, pentavalent antimonials and amphotericin B were the most analyzed drugs and showed therapeutic success; however, serious adverse events can occur due to their use. The prognostic factors identified were anemia, edema, bleeding, jaundice, age, and HIV coinfection. Conclusions. The evidence map developed shows rK39 ICT and DAT as promising diagnostic alternatives and reinforces the efficacy of liposomal amphotericin B and pentavalent antimonials. Insecticide-impregnated dog collars appear as a promising measure for the control of visceral leishmaniasis, but there is also a need for future studies and reviews with higher methodological quality, especially on prevention and control interventions.

RESUMEN Objetivo. Elaborar un mapa de evidencia sobre la prevención, el control, el diagnóstico, el tratamiento y el pronóstico de la leishmaniasis visceral. Métodos. Se realizaron búsquedas de revisiones sistemáticas sobre la leishmaniasis visceral en MEDLINE/PubMed y la Biblioteca Virtual en Salud. Tras la selección, cada revisión sistemática incluida fue sometida a evaluación, caracterización y categorización según tipo de intervención y resultados, de acuerdo con la metodología ofrecida por el Centro Latinoamericano y del Caribe de Información en Ciencias de la Salud de la OPS/OMS (BIREME). La calidad metodológica se evaluó con la herramienta AMSTAR2 para determinar el nivel de confianza de la información obtenida. Resultados. Entre las intervenciones de prevención y control, las más evaluadas fueron la fumigación con insecticidas, los mosquiteros, los collares para perros y el sacrificio de perros y se hizo hincapié en que los collares insecticidas para perros pueden reducir la incidencia de leishmaniasis visceral en perros. En cuanto al diagnóstico, la reacción en cadena de la polimerasa (PCR, por su sigla en inglés), la prueba inmunocromatográfica rK39 (rK39 ICT) y la prueba de aglutinación directa (DAT, por su sigla en inglés) mostraron alta sensibilidad y especificidad. Con respecto al tratamiento, los fármacos más analizados que arrojaron éxito terapéutico fueron los antimoniales pentavalentes y la anfotericina B; sin embargo, su uso puede provocar efectos adversos graves. Los factores pronósticos que se identificaron fueron anemia, edema, sangrado, ictericia, edad y coinfección por el VIH. Conclusiones. El mapa de evidencia elaborado presenta la prueba inmunocromatográfica rK39 y la prueba de aglutinación directa como alternativas diagnósticas prometedoras, y consolida la eficacia de la anfotericina B liposomal y los antimoniales pentavalentes. Los collares de perro impregnados de insecticida parecen ser una medida prometedora para el control de la leishmaniasis visceral, si bien también son necesarios estudios y revisiones adicionales de mayor calidad metodológica, especialmente sobre intervenciones de prevención y control.

RESUMO Objetivo. Desenvolver um mapa de evidências de prevenção, controle, diagnóstico, tratamento e prognóstico da leishmaniose visceral. Métodos. Foram realizadas buscas por revisões sistemáticas sobre leishmaniose visceral no MEDLINE/PubMed e na Biblioteca Virtual em Saúde. Após a seleção, cada revisão sistemática incluída foi avaliada, caracterizada e classificada por tipo de intervenção e por desfechos, de acordo com a metodologia oferecida pelo Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde (BIREME) da OPAS/OMS. A qualidade metodológica foi avaliada utilizando a ferramenta AMSTAR2 para determinar o nível de confiança das evidências obtidas. Resultados. Entre as intervenções de prevenção e controle, pulverização com inseticida, mosquiteiros, coleiras para cães e abate de cães foram as mais frequentemente avaliadas, com destaque para as coleiras inseticidas na redução da incidência de leishmaniose visceral em cães. Quanto ao diagnóstico, a reação em cadeia da polimerase (PCR), o teste imunocromatográfico rK39 (rK39 ICT) e o teste de aglutinação direta (DAT, sigla em inglês para direct agglutination test) apresentaram alta sensibilidade e especificidade. Em relação ao tratamento, os antimoniais pentavalentes e a anfotericina B foram os medicamentos mais analisados e demonstraram sucesso terapêutico, embora seu uso possa resultar em eventos adversos graves. Os fatores prognósticos identificados foram anemia, edema, sangramento, icterícia, idade e coinfecção com HIV. Conclusões. O mapa de evidências desenvolvido mostra o rK39 ICT e o DAT como alternativas promissoras para o diagnóstico e reforça a eficácia da anfotericina B lipossomal e dos antimoniais pentavalentes. As coleiras impregnadas com inseticida aparecem como medida promissora para o controle da leishmaniose visceral, mas estudos e revisões futuras com mais qualidade metodológica, especialmente sobre intervenções de prevenção e controle, são necessários.

Perfil de internações e óbitos hospitalares por síndrome respiratória aguda grave causada por COVID-19 no Piauí: estudo descritivo, 2020-2021 / Perfil de ingresos y fallecimientos hospitalarios por síndrome respiratorio agudo grave por COVID-19 en Piauí, Brasil: estudio descriptivo, 2020-2021 / Profile of hospital admissions and deaths due to severe acute respiratory syndrome caused by COVID-19 in Piauí, Brazil: a descriptive study, 2020-2021

Objetivo: Descrever o perfil e a variação temporal de internações e óbitos hospitalares por síndrome respiratória aguda grave (SRAG) por COVID-19 no Piauí, Brasil, segundo local de internação. Métodos: Estudo descritivo sobre dados do Sistema de Informação da Vigilância Epidemiológica da Gripe de 2020 a 2021. Calculou-se a letalidade entre registros hospitalares com desfecho e respectivos intervalos de confiança de 95% (IC95%). Resultados: Foram incluídos 12.649 indivíduos majoritariamente do sexo masculino (57,1%), negros (61,2%), com uma ou duas comorbidades (30,5%). No interior, entre registros hospitalares com desfecho, a letalidade para internados (44,1%; IC95% 42,0;46,3), admitidos em unidades de terapia intensiva (82,3%; IC95% 79,7;84,8) e indivíduos submetidos a ventilação mecânica invasiva (96,6%; IC95% 94,9;97,8) foi maior do que na capital do estado. Conclusão: O estudo permitiu a caracterização do perfil das internações devidas a SRAG por COVID-19 no Piauí e demonstrou elevada letalidade entre registros hospitalares com desfechos, mantendo-se alta no período estudado, sobretudo no interior.

Objetivo: Describir el perfil y variación temporal de los ingresos y fallecimientos hospitalarios por síndrome respiratorio agudo grave (SRAG) causado por COVID-19 en Piauí, Brasil, según el lugar de ingreso. Métodos: Estudio descriptivo con datos del Sistema de Información de Vigilancia Epidemiológica de la Gripe de 2020 a 2021. Se calculó la letalidad entre los registros hospitalarios con desenlace con intervalo de confianza del 95% (IC95%). Resultados: Se incluyeran 12.649 individuos que eran en su mayoría del sexo masculino (57,1%), negros (61,2%) y tenían una o dos comorbilidades (30,5%). La letalidad entre los registros hospitalarios con desenlace fue mayor en el interior, con proporciones de 44,1% (IC95% 42,0;46,3) en individuos hospitalizados, 82,3% (IC95% 79,7;84,8) en unidades de cuidados intensivos y 96,6% (IC95% 94,9;97,8) de los sometidos a ventilación mecánica invasiva. Conclusión: El estudio permitió caracterizar el perfil de hospitalizaciones por SRAG por COVID-19 en Piauí y mostró una alta letalidad entre los registros hospitalarios con desenlace, que se mantuvo alta durante el período de estudio, especialmente en el interior.

Objective: To describe the profile and temporal variation of hospital admissions and deaths due to severe acute respiratory syndrome (SARS) caused by COVID-19 in Piauí, Brazil, according to place of hospitalization. Methods: We performed a descriptive study using data from the Influenza Surveillance Information System between 2020 and 2021. Case fatality ratio among hospital records with outcome and respective 95% confidence intervals (95%CI) were calculated. Results: We included 12,649 individuals who were mostly male (57.1%), Black (61.2%) and had one or two comorbidities (30.5%). Case fatality ratio among hospital records with outcome was higher in the state's interior region than in its capital, with proportion of 44.1% (95%CI 42.0;46.3) for those who were hospitalized, 82.3% (95%CI 79.7;84.8) for those admitted to intensive care units and 96.6% (95%CI 94.9;97.8) for those undergoing invasive mechanical ventilation. Conclusion: The study enabled characterization of the profile of SARS hospitalizations due to COVID-19 in Piauí and demonstrated high case fatality ratio, among hospital records with outcome, which remained high during the study period, especially in the interior of the state.

DDX3 DEAD-box RNA helicase plays a central role in mitochondrial protein quality control in Leishmania.

DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death. Importantly, this phenotype is exacerbated upon oxidative stress in parasites forced to use the mitochondrial oxidative respiratory machinery. Furthermore, we show that in the absence of DDX3, levels of major components of the unfolded protein response as well as of polyubiquitinated proteins increase in the parasite, particularly in the mitochondrion, as an indicator of mitochondrial protein damage. Consistent with these findings, immunoprecipitation and mass-spectrometry studies revealed potential interactions of DDX3 with key components of the cellular stress response, particularly the antioxidant response, the unfolded protein response, and the AAA-ATPase p97/VCP/Cdc48, which is essential in mitochondrial protein quality control by driving proteosomal degradation of polyubiquitinated proteins. Complementation studies using DDX3 deletion mutants lacking conserved motifs within the helicase core support that binding of DDX3 to ATP is essential for DDX3's function in mitochondrial proteostasis. As a result of the inability of DDX3-depleted Leishmania to recover from ROS damage and to survive various stresses in the host macrophage, parasite intracellular development was impaired. Collectively, these observations support a central role for the Leishmania DDX3 homolog in preventing ROS-mediated damage and in maintaining mitochondrial protein quality control.

Perfil epidemiológico e tendência temporal da leishmaniose visceral: Piauí, Brasil, 2008 a 2018 / Epidemiological profile and time trend in visceral leishmaniasis: Piauí, Brazil, 2008-2018 / Perfil epidemiológico y tendencia temporal de la leishmaniasis visceral: Piauí, Brasil, 2008 a 2018

A leishmaniose visceral (LV) ou calazar é uma das principais doenças tropicais negligenciadas, de grande importância devido ao caráter letal desta zoonose causada por protozoários do gênero Leishmania. Objetivou-se analisar a tendência temporal dos casos de LV no Estado do Piauí, Brasil, de 2008 a 2018, inserindo-o dentro do período total de 1971 a 2018. Utilizaram-se dados do Sistema de Informação de Agravos de Notificação (SINAN) e do Sistema de Informações sobre Mortalidade (SIM). Para análise da carga da doença, foram coletados dados do Instituto de Métricas e Avaliação em Saúde através do estudo Carga Global de Doenças, Lesões e Fatores de Risco. Foi empregada a análise de regressão Prais-Winsten. Foram registrados 2.374 casos com provável local de infecção no Piauí e 2.492 casos em residentes do estado. A série histórica analisada, de 1971 a 2018, reafirma o caráter cíclico da doença, pela presença dos picos epidêmicos identificados em 1983 e 1984, 1993 e 1994, 2003 e 2004 e 2013 e 2014. Não foram identificadas alterações significativas na tendência dos coeficientes de incidência, mortalidade e letalidade no estado. No entanto, houve aumento significativo do coeficiente de incidência no Território de Desenvolvimento (TD) Chapada das Mangabeiras (variação percentual anual de 17,5%) e redução no TD Vale do Sambito (-18,3%) e TD Vale do Rio Guaribas (-8,1%). A LV tem a maior carga de doença medida em anos de vida ajustados por deficiência entre as doenças tropicais negligenciadas do estado. Recomenda-se o aprimoramento das medidas de vigilância e controle do agravo.

Visceral leishmaniasis (VL) or kala azar is one of the main neglected tropical diseases, of major importance due to the lethal nature of this zoonosis caused by protozoa of genus Leishmania. The study aimed to analyze the time trend in VL cases in the state of Piauí, Brazil, from 2008 to 2018, within the total period from 1971 to 2018. Data were obtained from the Brazilian Information System for Notificable Diseases (SINAN) and the Brazilian Mortality Information System (SIM). For burden of disease analysis, data were collected from the Institute for Health Metrics and Evaluation through the Global Burden of Diseases, Injuries, and Risk Factors (GBD Compare). Prais-Winsten regression analysis was used. A total of 2,374 cases were recorded with probable infection in the state of Piauí and 2,492 cases in residents of the state. The historical series analyzed, from 1971 to 2018, reaffirms the cyclical nature of the disease, based on the identification of epidemic peaks in 1983-1984, 1993-1994, 2003-2004, and 2013-2014. No significant alterations were identified in the trends in incidence, mortality, and case-fatality coefficients in the state. However, there was a significant increase in the incidence coefficient in the Chapada das Mangabeiras Development Territory, with an annual percent change of 17.5%, and a decrease in the Vale do Sambito Development Territory (-18.3%) and Vale do Rio Guaribas Development Territory (-8,1%). VL has a high burden of disease, measured by disability-adjusted life years, and is among the leading neglected tropical diseases in the state of Piauí. The study concludes by recommending the improvement of surveillance and control measures for this disease.

La leishmaniasis visceral (LV) o kala azar es una de las principales enfermedades tropicales desatendidas de gran importancia, debido al carácter letal de esta zoonosis causada por protozoos del género Leishmania. El objetivo fue analizar la tendencia temporal de los casos de LV en el estado de Piauí, Brasil, de 2008 a 2018, incluyéndola dentro del período total de 1971 a 2018. Se utilizaron datos del Sistema Brasileño de Información de Enfermedades de Notificación (SINAN) y del Sistema de Información sobre Mortalidad (SIM). Para el análisis de la carga de la enfermedad, se recogieron datos del Instituto de Métricas y Evaluación en Salud, a través del estudio Carga Global de Enfermedades, Lesiones y Factores de Riesgo (GBD Compare). Se empleó el análisis de regresión Prais-Winsten. Se registraron 2.374 casos con probable lugar de infección en Piauí y 2492 casos en residentes del estado. La serie histórica analizada, de 1971-2018, reafirma el carácter cíclico de la enfermedad por la presencia de los picos epidémicos, identificados en 1983 y 1984, 1993 y 1994, 2003 y 2004 y 2013 y 2014. No se identificaron alteraciones significativas en la tendencia de los coeficientes de incidencia, mortalidad y letalidad en el estado. No obstante, hubo un aumento significativo del coeficiente de incidencia en el Territorio de Desarrollo (TD) Chapada das Mangabeiras (variación del porcentaje anual de 17,5%) y reducción en el TD Vale do Sambito (-18,3%) y TD Vale do Rio Guaribas (-8,1%). La LV tiene una mayor carga de enfermedad medida en años de vida ajustados por deficiencia entre las enfermedades tropicales olvidadas del estado. Se recomienda el perfeccionamiento de las medidas de vigilancia y control de la enfermedad.

Smartphone serious games for vision and hearing assessment.

Falls are the second leading cause of accidental injury deaths worldwide. In this paper, it is intended to define methodologies that permit the evaluation of two potential factors which might have an impact on fall risk, these are: visual and hearing loss. The aim of the work developed is not to replace clinic visits, but to offer the user the means to continue the tracking of his vision and hearing at home, during the long time intervals between clinical tests. Tests conducted in a sample of our target users indicate a good ability to measure vision and hearing using an android smartphone and the proposed methodologies. While some tests require further validation, promising results were achieved in the most common tests for vision and hearing, presenting a good correlation between the system's results when compared to the traditional tests (for distance visual acuity) and the data gathered from the users (for hearing tests).

Convergent evolution at the gametophytic self-incompatibility system in Malus and Prunus.

S-RNase-based gametophytic self-incompatibility (GSI) has evolved once before the split of the Asteridae and Rosidae. This conclusion is based on the phylogenetic history of the S-RNase that determines pistil specificity. In Rosaceae, molecular characterizations of Prunus species, and species from the tribe Pyreae (i.e., Malus, Pyrus, Sorbus) revealed different numbers of genes determining S-pollen specificity. In Prunus only one pistil and pollen gene determine GSI, while in Pyreae there is one pistil but multiple pollen genes, implying different specificity recognition mechanisms. It is thus conceivable that within Rosaceae the genes involved in GSI in the two lineages are not orthologous but possibly paralogous. To address this hypothesis we characterised the S-RNase lineage and S-pollen lineage genes present in the genomes of five Rosaceae species from three genera: M. × domestica (apple, self-incompatible (SI); tribe Pyreae), P. persica (peach, self-compatible (SC); Amygdaleae), P. mume (mei, SI; Amygdaleae), Fragaria vesca (strawberry, SC; Potentilleae), and F. nipponica (mori-ichigo, SI; Potentilleae). Phylogenetic analyses revealed that the Malus and Prunus S-RNase and S-pollen genes belong to distinct gene lineages, and that only Prunus S-RNase and SFB-lineage genes are present in Fragaria. Thus, S-RNase based GSI system of Malus evolved independently from the ancestral system of Rosaceae. Using expression patterns based on RNA-seq data, the ancestral S-RNase lineage gene is inferred to be expressed in pistils only, while the ancestral S-pollen lineage gene is inferred to be expressed in tissues other than pollen.

Genes belonging to the insulin and ecdysone signaling pathways can contribute to developmental time, lifespan and abdominal size variation in Drosophila americana.

Even within a single genus, such as Drosophila, cases of lineage-specific adaptive evolution have been found. Therefore, the molecular basis of phenotypic variation must be addressed in more than one species group, in order to infer general patterns. In this work, we used D. americana, a species distantly-related to D. melanogaster, to perform an F2 association study for developmental time (DT), chill-coma recovery time (CRT), abdominal size (AS) and lifespan (LS) involving the two strains (H5 and W11) whose genomes have been previously sequenced. Significant associations were found between the 43 large indel markers developed here and DT, AS and LS but not with CRT. Significant correlations are also found between DT and LS, and between AS and LS, that might be explained by variation at genes belonging to the insulin and ecdysone signaling pathways. Since, in this F2 association study a single marker, located close to the Ecdysone receptor (EcR) gene, explained as much as 32.6% of the total variation in DT, we performed a second F2 association study, to determine whether large differences in DT are always due to variation in this genome region. No overlapping signal was observed between the two F2 association studies. Overall, these results illustrate that, in D. americana, pleiotropic genes involved in the highly-conserved insulin and ecdysone signaling pathways are likely responsible for variation observed in ecologically relevant phenotypic traits, although other genes are also involved.