RESUMO
OBJECTIVE: To test the short-term impact of Conexiones, a culturally adapted cancer parenting education program for diagnosed child-rearing Hispanic mothers. DESIGN: Single group, pre-post-test design. SAMPLE: 18 U.S. Hispanic mothers diagnosed within 2 years with early-stage cancer (0-III) raising a child (5-17 years). METHODS: Participants completed consent, baseline measures, and five telephone-delivered Conexiones sessions at 2-week intervals from trained patient educators in English or Spanish. Outcomes were assessed at baseline and at 3 months. RESULTS: Maternal depressed mood, parenting self-efficacy, and parenting quality significantly improved. Children's anxious/depressed mood tended to significantly improve. Outcomes did not co-vary with mothers' level of acculturation. CONCLUSIONS: Conexiones appears to positively improve Hispanic mothers' distress and parenting competencies; efficacy testing is warranted within a larger randomized control trial. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: A brief, culturally adapted cancer parenting education program has potential to enhance Hispanic mothers' and children's behavioral-emotional adjustment to a mother's cancer.
Assuntos
Mães , Neoplasias , Feminino , Humanos , Mães/psicologia , Poder Familiar/psicologia , Estudos de Viabilidade , Hispânico ou Latino , Neoplasias/terapia , Educação não Profissionalizante , TelefoneRESUMO
The purpose of the present study was to evaluate the efficacy of the treatment with a recombinant cysteine proteinase from Leishmania, rldccys1, associated with allopurinol or miltefosine on Leishmania (Leishmania) infantum chagasi-infected hamsters. Golden Syrian hamsters infected with L. (L.) infantum chagasi were treated with either miltefosine (46 mg/kg) or allopurinol (460 mg/kg) alone by oral route or associated with rldccys1 (150 µg/hamster) by subcutaneous route for 30 days. Infected hamsters were also treated with miltefosine (46 mg/kg) plus rldccys1 (150 µg/hamster) for 30 days (phase 1) followed by two additional doses of rldccys1 (250 µg/hamster) (phase 2). After the end of treatment, the animals were analyzed for parasite load, body weight, serum levels of immunoglobulins, cytokine expression, and drug toxicity. The data showed a significant decrease of parasite load in infected hamsters treated with allopurinol or miltefosine alone or associated with rldccys1, as well as in those treated with rldccys1 alone. Significantly lower levels of serum IgG were detected in hamsters treated with allopurinol plus rldccys1. The treatment with miltefosine associated with rldccys1 prevented relapse observed in animals treated with miltefosine alone. A significant loss of body weight was detected only in some hamsters treated with miltefosine for 1 month and deprived of this treatment for 15 days. There were no significant differences in transcript expression of IFN-γ and IL-10 in any of treated groups. Neither hepatotoxicity nor nephrotoxicity was observed among controls and treated groups. These findings open perspectives to further explore this immunochemotherapeutic schedule as an alternative for treatment of visceral leishmaniasis.
Assuntos
Antiprotozoários , Leishmania infantum , Leishmaniose Visceral , Alopurinol/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Peso Corporal , Cricetinae , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Mesocricetus , Fosforilcolina/uso terapêuticoRESUMO
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the German language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. The participating centres were asked to collect demographic and clinical data along the JAMAR questionnaire in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 319 JIA patients (2.8% systemic, 36.7% oligoarticular, 23.5% RF negative polyarthritis, and 37% other categories) and 100 healthy children were enrolled in eight centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the German version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research.
Assuntos
Artrite Juvenil/diagnóstico , Avaliação da Deficiência , Medidas de Resultados Relatados pelo Paciente , Reumatologia/métodos , Adolescente , Idade de Início , Artrite Juvenil/fisiopatologia , Artrite Juvenil/psicologia , Artrite Juvenil/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Características Culturais , Feminino , Alemanha , Nível de Saúde , Humanos , Masculino , Pais/psicologia , Pacientes/psicologia , Valor Preditivo dos Testes , Prognóstico , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , TraduçãoRESUMO
In response to nutrient shortage or organelle damage, cells undergo macroautophagy. Starvation of glucose, an essential nutrient, is thought to promote autophagy in mammalian cells. We thus aimed to determine the role of autophagy in cell death induced by glucose deprivation. Glucose withdrawal induces cell death that can occur by apoptosis (in Bax, Bak-deficient mouse embryonic fibroblasts or HeLa cells) or by necrosis (in Rh4 rhabdomyosarcoma cells). Inhibition of autophagy by chemical or genetic means by using 3-methyladenine, chloroquine, a dominant negative form of ATG4B or silencing Beclin-1, Atg7, or p62 indicated that macroautophagy does not protect cells undergoing necrosis or apoptosis upon glucose deprivation. Moreover, glucose deprivation did not induce autophagic flux in any of the four cell lines analyzed, even though mTOR was inhibited. Indeed, glucose deprivation inhibited basal autophagic flux. In contrast, the glycolytic inhibitor 2-deoxyglucose induced prosurvival autophagy. Further analyses indicated that in the absence of glucose, autophagic flux induced by other stimuli is inhibited. These data suggest that the role of autophagy in response to nutrient starvation should be reconsidered.
Assuntos
Autofagia/fisiologia , Fibroblastos/metabolismo , Glucose/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Antimetabólitos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Proteína Beclina-1 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisteína Endopeptidases/metabolismo , Desoxiglucose/farmacologia , Glucose/farmacologia , Células HeLa , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Sequestossoma-1 , Edulcorantes/metabolismo , Edulcorantes/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Transcrição TFIIH , Fatores de Transcrição/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismoRESUMO
Wastewater surveillance represents an alternative approach to regulating contamination and the early detection of infectious agents and outbreaks of diseases of public health importance. This study evaluated domestic wastewater effects on recreational waters in estuarine and seawater bodies in Guayas and Santa Elena provinces in Ecuador, South America. Fecal indicator bacteria (thermotolerant coliforms) served as key indicators for evaluation. Physical, chemical, and microbiological quality markers following the Ecuadorian environmental quality standard and the discharge of effluents to the water resource were analyzed. Samples were collected from 44 coastal sites and 2 oxidation lagoons during the dry and rainy seasons of 2020 and 2021, respectively. SARS-CoV-2 RNA was detected in samples with higher E. coli concentrations using reverse transcription quantitative PCR to detect the genes N and ORF1ab. All samples analyzed for SARS-CoV-2 showed Ct Ë 40 for at least one gene. Four samples showed at least 20 genome copies of gene N per reaction. These were at an artisanal fishing port, an estuarine area (Palmar), a recreational bay, and an oxidation lagoon. A moderate correlation was found between SARS-CoV-2 RNA, thermotolerant coliform and E. coli (p-value ≤ 0.0037), and a strong and positive correlation between thermotolerant coliform and E. coli. (p-value ≤ 0.00001), highlighting the utility of these established parameters as a proxy of the virus. Significant differences were found in the concentrations of thermotolerant coliforms between seasons (p-value = 0.016) and sites (p-value = 0.005). The highest levels of coliforms were found in the dry season (63000 MPN/100 mL) in Anconcito and during the rainy season (14000 MPN/100 mL) at Esterillo in Playas County. It is recommended that the decentralized autonomous governments of the surveyed provinces in Ecuador implement urgent corrective actions and establish medium-term mechanisms to minimize a potential contamination route. Additional parameters must be included in the monitoring, such as Enterococcus and intestinal parasites, due to their public health implications. In the oxidation lagoons, maintenance actions must be carried out, including the dissolution of sediments, an increase in water retention times, and in situ treatment of the sludge, to improve the system's performance.
Assuntos
COVID-19 , RNA Viral , SARS-CoV-2 , Esgotos , Qualidade da Água , Equador , Esgotos/virologia , Esgotos/microbiologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , RNA Viral/análise , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/genética , Microbiologia da Água , Monitoramento Ambiental/métodos , Água do Mar/virologia , Água do Mar/microbiologia , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Águas Residuárias/virologia , Águas Residuárias/microbiologiaRESUMO
OBJECTIVE: To assess the impact of the COVID-19 pandemic on routine childhood vaccination coverage in Colombia by age group, rural/urban residence, state and vaccine type. DESIGN: Ecological study of official monthly vaccination records. SETTING: Vaccination records from the Colombian Ministry of Health (March-October 2019 and 2020). PARTICIPANTS: Aggregated data for Colombian children (<12 months, n=676 153; 12-23 months, n=700 319; and 5 years, n=734 295) participating in the Expanded Program on Immunization. MAIN OUTCOME MEASURES: Proportion of eligible population receiving vaccination. RESULTS: Vaccination coverage showed an overall decline of approximately 14.4% from 2019 to 2020 (2019 coverage=76.0, 2020 coverage=61.6%). The greatest reduction in proportion vaccinated was observed in children <12 months of age for pneumococcal vaccine (second dose) (2019 coverage=81.4%; 2020 coverage=62.2%; 2019-2020 absolute difference, 19.2%; 95% CI 14.8% to 23.7%). For children aged 12-23 months, the proportion vaccinated for yellow fever declined by 16.4% (12.4% to 20.9%) from 78.3% in 2019 to 61.8% in 2020. Among children 5 years of age, the biggest decrease occurred for the oral polio vaccine (second dose), with a difference of 11.4% (7.1% to 15.7%) between 2019 and 2020 (73.1% and 61.7% for 2019 and 2020). We observed a statistically significant effect on vaccine coverage in rural versus urban areas for children <12 months and 5 years of age. CONCLUSIONS: Reduced uptake of immunisations during the COVID-19 pandemic poses a serious risk of vaccine-preventable disease outbreaks. Colombia and other middle-income countries need to continue to monitor immunisation programme coverage and disease outbreaks at the national and subnational levels and undertake catch-up vaccination activities.
Assuntos
COVID-19/epidemiologia , Programas de Imunização , Pandemias , Cobertura Vacinal , Doenças Preveníveis por Vacina/prevenção & controle , Pré-Escolar , Colômbia/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Lactente , Aceitação pelo Paciente de Cuidados de Saúde , População Rural , SARS-CoV-2 , População UrbanaRESUMO
BACKGROUND: The infant gut microbiota establishes during a critical window of opportunity when metabolic and immune functions are highly susceptible to environmental changes, such as diet. Human milk oligosaccharides (HMOs) for instance are suggested to be beneficial for infant health and gut microbiota. Infant formulas supplemented with the HMOs 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) reduce infant morbidity and medication use and promote beneficial bacteria in the infant gut ecosystem. To further improve infant formula and achieve closer proximity to human milk composition, more complex HMO mixtures could be added. However, we currently lack knowledge about their effects on infants' gut ecosystems. METHOD: We assessed the effect of lactose, 2'-FL, 2'-FL + LNnT, and a mixture of six HMOs (HMO6: consisting of 2'-FL, LNnT, difucosyllactose, lacto-N-tetraose, 3'- and 6'-sialyllactose) on infant gut microbiota and intestinal barrier integrity using a combination of in vitro models to mimic the microbial ecosystem (baby M-SHIME®) and the intestinal epithelium (Caco-2/HT29-MTX co-culture). RESULTS: All the tested products had bifidogenic potential and increased SCFA levels; however, only the HMOs' fermented media protected against inflammatory intestinal barrier disruption. 2'-FL/LNnT and HMO6 promoted the highest diversification of OTUs within the Bifidobactericeae family, whereas beneficial butyrate-producers were specifically enriched by HMO6. CONCLUSION: These results suggest that increased complexity in HMO mixture composition may benefit the infant gut ecosystem, promoting different bifidobacterial communities and protecting the gut barrier against pro-inflammatory imbalances.
Assuntos
Microbioma Gastrointestinal , Leite Humano , Células CACO-2 , Ecossistema , Humanos , Lactente , Fórmulas Infantis , Lactose/metabolismo , Lactose/farmacologia , Leite Humano/metabolismo , Oligossacarídeos/metabolismoRESUMO
INTRODUCTION: The Latin American Society of Pediatric Infectious Diseases (SLIPE by its Spanish acronyms) is working to understand the current situation, gaps, and opportunities for traceability of the quality vaccination process in Latin America and the Caribbean. AREAS COVERED: On September 24th and 25th, a Latin American forum of experts in immunization programs was held through the Zoom platform; the topics discussed included: computerized systems for recording immunizations, vaccination programs traceability, challenges, and information systems for the integrated management of vaccination. EXPERT OPINION: Latin American countries have transitioned from having a nominal registration system to a nominal tracking system, with many of them not migrating their platforms to new technologies; therefore, the low-quality data, fragmented databases, and slow information traffic present a challenge that must be taken on.
Assuntos
Programas de Imunização , Vacinação , Região do Caribe , Humanos , Imunização , América LatinaRESUMO
A 500 bp fragment encoding an isoform of cysteine proteinase from Leishmania (Leishmania) amazonensis was subcloned and expressed in the pHis vector, resulting in a recombinant protein of 24 kDa, rLacys24. In Western blots of L. (L.) amazonensis extracts, antibodies directed to rLacys24 recognized a cysteine proteinase isoform of 30 kDa. Analysis by fluorescence-activated cell sorter showed a significantly higher expression of CD8(+) lymphocytes in animals immunized with rLacys24 plus CFA, whereas a low expression of CD4(+) lymphocytes was observed in these animals. The cytotoxicity of lymphocytes isolated from mice immunized with rLacys24 plus CFA on L. (L.) amazonensis-infected macrophages was significantly higher than that observed in the presence of lymphocytes from control animals. Immunization of BALB/c mice with rLacys24 plus CFA resulted in a low but significant decrease of foot lesions after challenge with L. (L.) amazonensis compared to those exhibited by control mice.
Assuntos
Cisteína Proteases/imunologia , Leishmania mexicana/enzimologia , Leishmania mexicana/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/prevenção & controle , Animais , Western Blotting , Cricetinae , Cisteína Proteases/genética , Cisteína Proteases/isolamento & purificação , DNA de Protozoário/química , Modelos Animais de Doenças , Eletroforese em Gel de Poliacrilamida , Feminino , Regulação Enzimológica da Expressão Gênica , Leishmania mexicana/genética , Linfonodos/citologia , Linfonodos/imunologia , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Linfócitos T/imunologiaRESUMO
BACKGROUND: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis. METHODS: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-ß from the treated macrophages were studied. RESULTS AND DISCUSSION: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 µg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 µg/mL). In addition, TGF-ß was significantly reduced after the treatment with all toxins evaluated. CONCLUSION: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.
Assuntos
Antiprotozoários , Venenos de Crotalídeos/química , Crotalus , Leishmania/crescimento & desenvolvimento , Leishmaniose/tratamento farmacológico , Proteínas de Répteis , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Feminino , Leishmaniose/metabolismo , Leishmaniose/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Répteis/química , Proteínas de Répteis/isolamento & purificação , Proteínas de Répteis/farmacologiaRESUMO
A recombinant protein, rLdccys1, produced by expression of the gene encoding a 30kDa cysteine proteinase from Leishmania (Leishmania) chagasi, was used to detect specific antibodies in serum by enzyme-linked immunosorbent assays and to test for reactivity in delayed-type hypersensitivity (DTH) responses of dogs from an endemic region of visceral leishmaniasis (VL), Teresina, Piauí State, Brazil. Amastigote or promastigote extracts were also assayed for comparison. The sensitivity for detection of specific antibodies to L. (L.) chagasi using rLdccys1, lysates from L. (L.) chagasi promastigotes and amastigotes was 96%, 68%, and 69%, respectively. No cross-reactivity between rLdccys1 and Chagas disease was observed, and little reactivity was found with sera from dogs with babesiosis and ehrlichiosis. Among 106 sera from symptomatic dogs and 22 from non-infected controls, no false negatives and only two false positive sera were found for rLdccys1. In contrast, amastigote lysates yielded 11 false positives and 13 false negatives, whereas the corresponding numbers for promastigote lysates were 17 and 16. DTH responses were determined after intradermal injection of rLdccys1 or amastigote extract and the induration area was measured at 24, 48 and 72h after injection. All asymptomatic dogs showed a positive intradermal response to rLdccys1 (>10mm) which peaked at 48h, whereas no significant reactivity to the recombinant antigen was found in the symptomatic group. Histological analysis of the intradermal induration showed a predominance of necrotic and hemorrhagic areas in sections from asymptomatic dogs injected with L. (L.) chagasi amastigote extract, whereas a typical granulomatous reaction mediated by mononuclear cells was observed in sections from asymptomatic animals injected with rLdccys1. Grouping data from ELISA and DTH assays with rLdccys1 and L. (L.) chagasi amastigote extracts showed that humoral and cellular responses were inversely correlated during the development of canine VL. Overall, these findings indicate that L. (L.) chagasi recombinant cysteine proteinase is potentially useful for diagnosis of canine VL, as well as for the discrimination of clinical and subclinical forms of the disease.
Assuntos
Cisteína Endopeptidases/imunologia , Doenças do Cão/diagnóstico , Leishmania/enzimologia , Leishmaniose Visceral/veterinária , Proteínas Recombinantes/imunologia , Testes Sorológicos/veterinária , Animais , Cricetinae , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Doenças do Cão/parasitologia , Cães , Feminino , Regulação Enzimológica da Expressão Gênica , Hipersensibilidade Tardia/veterinária , Leishmaniose Visceral/diagnóstico , Masculino , Sensibilidade e EspecificidadeRESUMO
Introduction: Human vitamin D levels have been increasingly related to a wide range of clinical outcomes. There is a large amount of reports on its associations, especially with obstetric complications, including preeclampsia and gestational diabetes. These results are scarcely consistent and there is still a lack of quality intervention studies to confirm the role of vitamin D in those outcomes. Objective: To review the available scientific evidence on the role of maternal vitamin D in the development of preeclampsia. Materials and methods: The methodology used followed the recommendations of the Cochrane guide for the preparation of systematic reviews, and for metaanalysis, the Guide of the Metaanalysis of Observational Studies in Epidemiology group (MOOSE). The search included both observational studies and controlled clinical trials. Results: Low vitamin D levels, measured by the 25-hydroxyvitamin D test, are common in pregnancy. The results of this systematic review and metaanalysis suggest an inverse ratio between vitamin D levels and the development of preeclampsia. There was heterogeneity among the studies with regard to the design, population, geographic location, definitions of exposure, and the outcome. We excluded randomized controlled trials from this meta-analysis. Conclusion: The inverse association we found suggests that the higher the levels of vitamin D the lesser the probability of developing preeclampsia, in spite of the heterogeneity of the global measurement in this type of analysis.
Introducción: Cada vez son más los hallazgos sobre la relación entre las concentraciones de vitamina D en el ser humano y diversas condiciones clínicas. Hay una gran cantidad de estudios que informan sobre dicha asociación, especialmente con complicaciones obstétricas, incluidas la preeclampsia y la diabetes mellitus de la gestación, entre otras, pero sus resultados todavía no son definitivos, por lo que se requieren estudios de intervención de calidad que confirmen la relación de la vitamina D con dichos resultados. Objetivo: Revisar la información plasmada en estudios en torno al papel de la vitamina D materna y el desarrollo de la preeclampsia. Materiales y métodos: La metodología usada siguió las recomendaciones de la guía Cochrane para la elaboración de revisiones sistemáticas y de la guía del grupo Meta-analysis of Observational Studies in Epidemiology (MOOSE) para los metaanálisis. La búsqueda incluyó estudios observacionales y ensayos clínicos controlados. Resultados: Los niveles bajos de vitamina D, medida con el examen de 25-hidroxivitamina D, son comunes en el embarazo. Los resultados de esta revisión sistemática y del metaanálisis sugieren una asociación inversa entre los niveles de vitamina D y el desarrollo de preeclampsia. Hubo heterogeneidad en los estudios en cuanto a su diseño, población y ubicación geográfica, así como a las definiciones de exposición y resultado. Los ensayos clínicos controlados aleatorizados se excluyeron del metaanálisis. Conclusión: Se encontró una asociación inversa que sugiere que, a mayores concentraciones de vitamina D, menor es la probabilidad de desarrollar preclampsia, a pesar de la heterogeneidad de la medida global en este tipo de análisis.
Assuntos
Pré-Eclâmpsia , Deficiência de Vitamina D , Vitamina D , Vitaminas , Feminino , Humanos , Gravidez , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitaminas/sangueRESUMO
BACKGROUND: Currently, the waist-to-height ratio (WHtR) has emerged as a practical and useful indicator for identifying cardiometabolic risk in child and adolescent population. OBJECTIVE: To evaluate the association between the WHtR and cardiometabolic risk factors (CMRFs) in a cohort of children in Bucaramanga, Colombia. METHODS: Analytical cross-sectional study. Child population between 6-10 years old from Bucaramanga (n = 1,282). Dependent variables: hypertension, pre-hypertension, overweight/obesity, impaired glucose, insulin resistance and dyslipidemia. Main independent variable: waist-toheight ratio. The association between dependent and independent variables was evaluated using binomial regression models. RESULTS: 9.77% of the children presented a WHtR of risk (95% CI: 8.19% to 11.52%). After adjustment for age, sex, socioeconomic status and physical activity, the WHtR of risk was significantly associated with lower HDL levels and higher levels of triglycerides, insulin resistance, hypertension and pre-hypertension (PR = 2.46 95% CI :1.70 to 3.55, p = 0.000, PR = 2.24 95% CI: 1.50 to 3.35, p = 0.000, PR = 9.39 95% CI: 5.40 to 16.30, p = 0.000, PR = 8.03 95% CI: 2.01 to 32.07, p = 0.003 y PR = 2.67 95% CI: 1.60 to 4.47, p = 0.000, respectively). CONCLUSION: Children with WHtR of risk were more likely to develop high levels of blood pressure and triglycerides, insulin resistance and lower levels of HDL.
Assuntos
Cardiopatias/epidemiologia , Doenças Metabólicas/epidemiologia , Relação Cintura-Quadril , Criança , Estudos de Coortes , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Fatores SocioeconômicosRESUMO
Exoantigens (exo) from Leptomonas seymouri and Crithidia fasciculata were used in an enzyme linked immunosorbent assay (ELISA), showing 100% reactivity with sera from visceral leishmaniasis (VL) cases, and no reactivity with American tegumentary leishmaniasis (ATL) ones. Our results have indicated that these exoantigens can be applied in the discrimination of VL and ATL cases.
Assuntos
Antígenos de Protozoários/sangue , Crithidia fasciculata/imunologia , Leishmania donovani/imunologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Visceral/diagnóstico , Trypanosomatina/imunologia , Anticorpos Antiprotozoários/sangue , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/parasitologiaRESUMO
Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the unfolded protein response transcription factors ATF4 and CHOP. This was associated with the nontranscriptional accumulation of TRAIL receptor 1 (TRAIL-R1) (DR4) and with the ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling. Consistent with this, the ablation of TRAIL-R1, TRAIL-R2, FADD, Bid, and caspase-8 attenuated cell death, although the downregulation of TRAIL did not, suggesting ligand-independent activation of TRAIL receptors. These data indicate that stress triggered by glucose deprivation promotes the ATF4-dependent upregulation of TRAIL-R2/DR5 and TRAIL receptor-mediated cell death.
Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Apoptose , Estresse do Retículo Endoplasmático , Glucose/deficiência , Neoplasias/patologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HeLa , Humanos , Neoplasias/metabolismo , Fator de Transcrição CHOP/metabolismoRESUMO
Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2-DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell types. In contrast, under normoxia, 2-DG at a low-concentration is not toxic in most carcinomas tested, but induces growth inhibition, which is primarily due to ER stress. Here we find a synergistic toxic effect in several tumor cell lines in vitro combining 2-DG with fenofibrate (FF), a drug that has been safely used for over 40 years to lower cholesterol in patients. This combination induces much greater energy stress than either agent alone, as measured by ATP reduction, increased p-AMPK and downregulation of mTOR. Inhibition of mTOR results in blockage of GRP78 a critical component of the unfolded protein response which we speculate leads to greater ER stress as observed by increased p-eIF2α. Moreover, to avoid an insulin response and adsorption by the liver, 2-DG is delivered by slow-release pump yielding significant anti-tumor control when combined with FF. Our results provide promise for developing this combination clinically and others that combine 2-DG with agents that act synergistically to selectively increase energy and ER stress to a level that is toxic to numerous tumor cell types.
Assuntos
Apoptose/efeitos dos fármacos , Desoxiglucose/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fenofibrato/farmacologia , Glicólise/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular Tumoral , Sinergismo Farmacológico , Chaperona BiP do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , Humanos , Hipolipemiantes/farmacologia , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
O objetivo desta revisão sistemática foi analisar o efeito do treinamento combinado na pressão arterial de idosos hipertensos. As buscas foram realizadas em novembro de 2021 nas bases de dados: National library of medicine, Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online, Literatura Latino-Americana e do Caribe em Ciências da Saúde e Scopus. Os critérios de inclusão foram: ensaios clínicos randomizados; população com idade ≥60 anos e com diagnóstico de hipertensão arterial; exercício combinado como intervenção; pressão arterial como um dos desfechos; publicados no idioma inglês e/ou português entre 2007 e 2021 e disponíveis em texto completo. Após as buscas, foram identificados 991 artigos científicos. Destes, 9 estudos foram selecionados por atenderam ao objetivo e aos critérios propostos. O tamanho das amostras variou de 20-115 participantes, com média de 48,7 ± 29,8. Todos os estudos foram conduzidos com idosos; 44,4% foram realizados com população somente do sexo feminino e 22,2% dos estudos com população do sexo masculino. No que se refere ao período de realização da intervenção, observou-se que o treinamento combinado foi executado desde uma única sessão até 16 semanas, numa frequência de três vezes por semana. Os estudos apontaram que após a realização do treinamento combinado, ocorreram reduções significativas nos valores de pressão arterial sistólica e diastólica. Apesar do treinamento combinado ter contribuído significativamente para reduzir os valores de pressão arterial, os resultados desta revisão sistemática devem ser interpretados com cautela, devido ao pequeno número de artigos inclusos e de suas respectivas limitações metodológicas. (AU)
The objective of this systematic review was to analyze the effect of combined training on blood pressure in hypertensive older adults. Searches were conducted in November 2021 in the databases: National library of medicine, Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online, Latin American and Caribbean Literature in Health Sciences, and Scopus. Inclusion criteria were: randomized clinical trials; population aged ≥60 years and diagnosed with hypertension; combined exercise as intervention; blood pressure as one of the endpoints; published in English and/or Portuguese between 2007 and 2021 and available in full text. After the searches, 991 scientific articles were identified. From those, 9 studies were selected as they met the objective and the research criteria. Sample sizes ranged from 20-115 participants, with a mean of 48.7 ± 29.8. All studies were performed with seniors; 44.4% were conducted with a femaleonly population and 22.2% of the studies with a male-only population. Regarding the period of the intervention, it was observed that the combined training was executed from a single session up to 16 weeks, three times a week. The studies indicated that after the combined training, there were significant reductions in the values of systolic and diastolic blood pressure. Although combined training contributed significantly to reduce blood pressure values, the results of this systematic review should be interpreted with caution due to the small number of articles included and their respective methodological limitations. (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Exercício Físico , Revisão , Pressão Arterial , Pressão Sanguínea , Idoso , HipertensãoRESUMO
A recombinant protein, rLdccys1, which was produced by expression of the gene encoding a 30 kDa cysteine proteinase from Leishmania (Leishmania) chagasi, was used for detection of antibodies in sera from patients with active visceral leishmaniasis (VL) in enzyme-linked immunosorbent assays. Analysis of the predicted amino acid sequence of rLdccys1 showed that it contains all the characteristics of a cysteine proteinase. The ability of the protein to react with sera from humans with VL was also shown by Western blotting. The sensitivity for detection of specific antibodies to L. (L.) chagasi bodies using rLdccys1, L. (L.) chagasi promastigote lysates, and amastigote lysates was 80%, 98%, and 99%, respectively. No cross-reactivity between rLdccys1 and Chagas disease was observed, and there was little positive reactivity with sera from patients with cutaneous leishmaniasis and tuberculosis, compared with promastigote and amastigote extracts. Our findings indicate that rLdccys1 from L. (L.) chagasi constitutes a potential tool for the diagnosis of American VL.
Assuntos
Anticorpos Antiprotozoários/sangue , Cisteína Endopeptidases/genética , Leishmania/genética , Leishmania/imunologia , Leishmaniose Visceral/diagnóstico , Sequência de Aminoácidos , Animais , Western Blotting , Estudos de Casos e Controles , Cricetinae , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leishmaniose Visceral/sangue , Mesocricetus , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Proteínas de Protozoários/genética , Proteínas Recombinantes/genética , Sensibilidade e Especificidade , Testes SorológicosRESUMO
Altered metabolism is a hallmark of cancer that opens new therapeutic possibilities. 2-deoxyglucose (2-DG) is a non-metabolizable glucose analog tested in clinical trials and is frequently used in experimental settings to mimic glucose starvation. However, in the present study, conducted in a rhabdomyosarcoma cell line, we find that 2-DG induces classical nuclear apoptotic morphology and caspase-dependent cell death, whereas glucose deprivation drives cells toward necrotic cell death. Necrosis induced by glucose deprivation did not resemble necroptosis or ferroptosis and was not prevented by antioxidants. Both stimuli promote endoplasmic reticulum stress. Moreover, the transcription factor ATF4 is found to mediate both the apoptosis induced by 2-DG and the glycosylation inhibitor tunicamycin, as well as the necrosis provoked by glucose withdrawal. Several hexoses partially prevented glucose deprivation-induced necrosis in rhabdomyosarcoma, although only mannose prevented apoptosis induced by 2-DG. In both cases, a reduction of cell death was associated with decreased levels of ATF4. Our results confirm previous data indicating the differential effects of these two forms with respect to inhibiting glucose metabolism, and they place endoplasmic reticulum stress as the critical mediator of glucose starvation-induced cell death.