RESUMEN

Identifying the factors that favor group living is central to studies of animal social behavior. One demographic parameter that is expected to substantially shape spatial and social relationships is population density. Specifically, high population densities may favor group living by constraining opportunities to live alone. In contrast, low densities may allow individuals to spread out within the habitat, leading to a reduction in the prevalence or size of social groups. Abrupt changes in density following natural catastrophic events provide important opportunities to evaluate the effects of population density on patterns of spatial and social organization. As part of long-term studies of the behavioral ecology of a population of highland tuco-tucos (Ctenomys opimus) at Monumento Natural Laguna de los Pozuelos, Jujuy Province, Argentina, we monitored the demographic and behavioral consequences of a flood that inundated our study site during December 2012. Unlike most species of Ctenomys studied to date, highland tuco-tucos are group living, meaning that multiple adults share burrow systems and nest sites. Despite a post-flood reduction in population density of ~75%, animals present on the study site during the 2013 breeding season continued to live in multi-adult social units (groups). No differences between pre- and post-flood home range sizes were detected and although between-unit spatial overlap was reduced in 2013, overlap within social units did not differ from that in pre-flood years. Animals assigned to the same social unit in 2013 had not lived together during 2012, indicating that post-flood groups were not simply the remnants of those present prior to the flood. Collectively, these findings indicate that group living in highland tuco-tucos is not driven by the density of conspecifics in the habitat. In addition to enhancing understanding of the adaptive bases for group living in Ctenomys, our analyses underscore the power of catastrophic events to generate insights into fundamental aspects of social behavior.

Asunto(s)

Densidad de Población , Conducta Social , Animales , Argentina , Ecosistema , Conducta Animal/fisiología , Inundaciones , Roedores/fisiología , Femenino , Masculino

RESUMEN

BACKGROUND: Although household contacts of patients with tuberculosis are known to be particularly vulnerable to tuberculosis, the published evidence focused on this group at high risk within the low-income and middle-income country context remains sparse. Using nationwide data from Brazil, we aimed to estimate the incidence and investigate the socioeconomic and clinical determinants of tuberculosis in a cohort of contacts of tuberculosis patients. METHODS: In this cohort study, we linked individual socioeconomic and demographic data from the 100 Million Brazilian Cohort to mortality data and tuberculosis registries, identified contacts of tuberculosis index patients diagnosed from Jan 1, 2004 to Dec 31, 2018, and followed up the contacts until the contact's subsequent tuberculosis diagnosis, the contact's death, or Dec 31, 2018. We investigated factors associated with active tuberculosis using multilevel Poisson regressions, allowing for municipality-level and household-level random effects. FINDINGS: We studied 420 854 household contacts of 137 131 tuberculosis index patients. During the 15 years of follow-up (median 4·4 years [IQR 1·9-7·6]), we detected 8953 contacts with tuberculosis. The tuberculosis incidence among contacts was 427·8 per 100 000 person-years at risk (95% CI 419·1-436·8), 16-times higher than the incidence in the general population (26·2 [26·1-26·3]) and the risk was prolonged. Tuberculosis incidence was associated with the index patient being preschool aged (<5 years; adjusted risk ratio 4·15 [95% CI 3·26-5·28]) or having pulmonary tuberculosis (2·84 [2·55-3·17]). INTERPRETATION: The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination. FUNDING: Wellcome Trust and Brazilian Ministry of Health.

Asunto(s)

Tuberculosis , Preescolar , Humanos , Estudios de Cohortes , Brasil/epidemiología , Incidencia , Tuberculosis/epidemiología , Factores de Riesgo , Trazado de Contacto

RESUMEN

INTRODUCTION: Housing-related factors can be predictors of health, including of diabetes outcomes. We analysed the association between subsidised housing residency and diabetes mortality among a large cohort of low-income adults in Brazil. RESEARCH DESIGN AND METHODS: A cohort of 9 961 271 low-income adults, observed from January 2010 to December 2015, was created from Brazilian administrative records of social programmes and death certificates. We analysed the association between subsidised housing residency and time to diabetes mortality using a Cox model with inverse probability of treatment weighting and regression adjustment. We assessed inequalities in this association by groups of municipality Human Development Index. Diabetes mortality included diabetes both as the underlying or a contributory cause of death. RESULTS: At baseline, the mean age of the cohort was 40.3 years (SD 15.6 years), with a majority of women (58.4%). During 29 238 920 person-years of follow-up, there were 18 775 deaths with diabetes as the underlying or a contributory cause. 340 683 participants (3.4% of the cohort) received subsidised housing. Subsidised housing residents had a higher hazard of diabetes mortality compared with non-residents (HR 1.17; 95% CI 1.05 to 1.31). The magnitude of this association was more pronounced among participants living in municipalities with lower Human Development Index (HR 1.30; 95% CI 1.04 to 1.62). CONCLUSIONS: Subsidised housing residents had a greater risk of diabetes mortality, particularly those living in low socioeconomic status municipalities. This finding suggests the need to intensify diabetes prevention and control actions and prompt treatment of the diabetes complications among subsidised housing residents, particularly among those living in low socioeconomic status municipalities.

Asunto(s)

Diabetes Mellitus , Vivienda , Humanos , Adulto , Femenino , Brasil/epidemiología , Estudios Retrospectivos , Diabetes Mellitus/epidemiología

RESUMEN

To study morphological evolution, it is necessary to combine information from multiple intersecting research fields. Here, we report on the structure of the bony and muscular elements of the craniomandibular complex of birds, highlighting its morphological architecture and complexity (or simplification) in the context of anatomical networks of the Band-winged Nightjar Systellura longirostris (Caprimulgiformes, Caprimulgidae). This species has skull osteology and jaw myology that departs from the general structural plan of the craniomandibular complex of Neornithes and is considered morphologically simple. Our goal is to test if its simplification is also reflected in its anatomical network, particularly in those parameters that measure complexity and to explore if the distribution of the networks in a phylomorphospace is conditioned by their evolutionary history or by convergence. Our results show that S. longirostris clusters with other Strisores and momotids and is segregated from the other bird species analyzed when plotted in the phylomorphospace, as a consequence of convergence in the network parameters. Systellura has a craniomandibular complex consisting of fewer muscles connecting more bones than the model species (e.g., the rock pigeon or the guira cuckoo). In this sense, Systellura is actually more complex regarding the number of integrative bony parts, while its craniomandibular complex is simpler. According to its anatomical network, Systellura also can be interpreted as less complex, particularly compared with other Strisores and taxa that reflect the general structure of the craniomandibular complex in Neornithes.

Asunto(s)

Estrigiformes , Animales , Cráneo/anatomía & histología , Estrigiformes/fisiología

RESUMEN

The antimicrobial photodynamic activity (aPDA) in fungal and bacterial strains of supramolecular adducts formed between the anionic photosensitizer (PS) Rose Bengal (RB2-) and aromatic polycations derived from (p-vinylbenzyl)triethylammonium chloride was evaluated. Stable supramolecular adducts with dissociation constants Kd ≈ 5 µM showed photosensitizing properties suitable for generating singlet oxygen (ΦΔ = 0.5 ± 0.1) with the added advantage of improving the photostability of the xanthenic dye. However, the aPDA of both free and supramolecular RB2- was highly dependent on the type of microorganism treated, indicating the importance of specific interactions between the different cell wall structures of the microbe and the PSs. Indeed, in the case of Gram-positive Staphylococcus aureus, the aPDA of molecular and supramolecular PSs was highly effective. Instead, in the case of Gram-negative Escherichia coli, only the RB2-:polycation adducts showed aPDA, while RB2- alone was inefficient, but in the case of Candida tropicalis, the opposite behavior was observed. Therefore, the present results indicate the potential of supramolecular chemistry to obtain aPDA à la carte depending on the target microbe and the PS properties.

Asunto(s)

Antiinfecciosos , Fotoquimioterapia , Antiinfecciosos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Polielectrolitos , Rosa Bengala/química , Rosa Bengala/farmacología , Oxígeno Singlete

RESUMEN

Notosuchia is a clade of crocodyliforms that was highly successful and diverse in the Cretaceous of Gondwana. Araripesuchus gomesii is a small notosuchian from the Early Cretaceous of Brazil that belongs to Uruguaysuchidae, one of the subgroups of notosuchians that first radiated, during the Aptian-Albian. Here we present a finite element analysis of A. gomesii based on a model reconstructed from CT scans and performed using published bone properties for crocodiles. The adductor musculature and their respective attachment areas were reconstructed based on Extant Phylogenetic Bracket. Different functional scenarios were tested applying an estimated 158 N bite force: unilateral bite, bilateral bite, pullback, head-shake, and head-twist. The results obtained were compared with those of Alligator mississippiensis, one of its closest living relatives. In the different simulations, the skull and lower jaws of Araripesuchus suffers more stress in the head-shake movement, followed by the unilateral and pullback bites with stress focalized in the premaxillary region. In contrast, the head-twist is the one with smaller stress values. Araripesuchus possess an oreinirostral skull that may provide greater overall resistance in the different scenarios on average, unlike Alligator that has a platyrostral skull with less resistance to dorsoventral mechanical loads. Previous hypotheses that considered A. gomesii as omnivorous coupled with our results, its small size, and likely limited bite force, suggest this taxon probably fed on small prey and other trophic items that could catch and handle entirely with its mouth, such as insects and small vertebrates.

Asunto(s)

Caimanes y Cocodrilos , Fuerza de la Mordida , Animales , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Filogenia , Cráneo/anatomía & histología

RESUMEN

BACKGROUND: Leprosy remains concentrated among the poorest communities in low-and middle-income countries and it is one of the primary infectious causes of disability. Although there have been increasing advances in leprosy surveillance worldwide, leprosy underreporting is still common and can hinder decision-making regarding the distribution of financial and health resources and thereby limit the effectiveness of interventions. In this study, we estimated the proportion of unreported cases of leprosy in Brazilian microregions. METHODOLOGY/PRINCIPAL FINDINGS: Using data collected between 2007 to 2015 from each of the 557 Brazilian microregions, we applied a Bayesian hierarchical model that used the presence of grade 2 leprosy-related physical disabilities as a direct indicator of delayed diagnosis and a proxy for the effectiveness of local leprosy surveillance program. We also analyzed some relevant factors that influence spatial variability in the observed mean incidence rate in the Brazilian microregions, highlighting the importance of socioeconomic factors and how they affect the levels of underreporting. We corrected leprosy incidence rates for each Brazilian microregion and estimated that, on average, 33,252 (9.6%) new leprosy cases went unreported in the country between 2007 to 2015, with this proportion varying from 8.4% to 14.1% across the Brazilian States. CONCLUSIONS/SIGNIFICANCE: The magnitude and distribution of leprosy underreporting were adequately explained by a model using Grade 2 disability as a marker for the ability of the system to detect new missing cases. The percentage of missed cases was significant, and efforts are warranted to improve leprosy case detection. Our estimates in Brazilian microregions can be used to guide effective interventions, efficient resource allocation, and target actions to mitigate transmission.

Asunto(s)

Lepra/epidemiología , Teorema de Bayes , Brasil/epidemiología , Humanos , Incidencia , Lepra/economía , Factores Socioeconómicos

RESUMEN

Sarcopenia, cachexia, and atrophy due to inactivity and disease states are characterized by a loss of skeletal muscle mass, often accompanied by reduced levels of anabolic hormones (e.g. testosterone). These conditions are associated with an increase in mortality, hospitalization and worsening in quality of life. Both physical exercise (EX) and anabolic-androgenic steroid (AAS) administration can improve the prognosis of patients as they increase physical functionality. However, there is a gap in the literature as to the impact of these therapies on the gains in strength and muscle mass and their implications for patient safety. Accordingly, we performed a random-effects meta-analysis to elucidate the effects of AAS and/or EX interventions on lean body mass (LBM) and muscle strength in conditions involving muscle loss. A systematic search for relevant clinical trials was conducted in MEDLINE, EMBASE, SCOPUS, Web of Science, and SPORTDiscus. Comparisons included AAS vs. Control, EX vs. Control, AAS vs. EX, AAS + EX vs. AAS and AAS + EX vs. EX. A total of 1114 individuals were analyzed. AAS increased LBM (effect size [ES]: 0.46; 95% CI: 0.25, 0.68, P = 0.00) and muscle strength (ES: 0.31; 95% CI: 0.08, 0.53, P = 0.01) when compared to a control group. EX promoted an increase in muscular strength (ES: 0.89; 95% CI: 0.53, 1.25, P = 0.00), with no effect on LBM when compared to the control group (ES: 0.15; 95% CI: -0.07, 0.38, P = 0.17). AAS did not demonstrate statistically significant differences when compared to EX for LBM and muscle strength. The combination of EX + AAS promoted a greater increase in LBM and muscular strength when compared to AAS or EX in isolation. Qualitatively, AAS administration had relatively few side effects. Significant heterogeneity was found in some analyses, which may be explained by the use of different AAS types and EX protocols. Our findings suggest that AAS administration in cachectic and sarcopenic conditions may be a viable interventional strategy to enhance muscle function when exercise is not a possible approach. Moreover, combining AAS with exercise may enhance positive outcomes in this population.

Asunto(s)

Anabolizantes , Testosterona , Ejercicio Físico , Humanos , Músculo Esquelético , Calidad de Vida

RESUMEN

INTRODUCTION: Tuberculosis incidence is disproportionately high among people in poverty. Cash transfer programs have become an important strategy in Brazil fight inequalities as part of comprehensive poverty alleviation policies. This study was aimed at assessing the effect of being a beneficiary of a governmental cash transfer program on tuberculosis (TB) treatment cure rates. METHODS: We conducted a longitudinal database study including people ≥18 years old with confirmed incident TB in Brazil in 2015. We treated missing data with multiple imputation. Poisson regression models with robust variance were carried out to assess the effect of TB determinants on cure rates. The average effect of being beneficiary of cash transfer was estimated by propensity-score matching. RESULTS: In 2015, 25,084 women and men diagnosed as new tuberculosis case, of whom 1,714 (6.8%) were beneficiaries of a national cash transfer. Among the total population with pulmonary tuberculosis several determinants were associated with cure rates. However, among the cash transfer group, this association was vanished in males, blacks, region of residence, and people not deprived of their freedom and who smoke tobacco. The average treatment effect of cash transfers on TB cure rates, based on propensity score matching, found that being beneficiary of cash transfer improved TB cure rates by 8% [Coefficient 0.08 (95% confidence interval 0.06-0.11) in subjects with pulmonary TB]. CONCLUSION: Our study suggests that, in Brazil, the effect of cash transfer on the outcome of TB treatment may be achieved by the indirect effect of other determinants. Also, these results suggest the direct effect of being beneficiary of cash transfer on improving TB cure rates.

Asunto(s)

Bases de Datos Factuales , Programas de Gobierno/economía , Pobreza , Tuberculosis Pulmonar , Adulto , Anciano , Brasil/epidemiología , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Tuberculosis Pulmonar/economía , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/terapia

RESUMEN

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a threat for the global TB epidemic control. Despite existing evidence that individualized treatment of MDR-TB is superior to standardized regimens, the latter are recommended in Brazil, mainly because drug-susceptibility tests (DST) are often restricted to first-line drugs in public laboratories. We compared treatment outcomes of MDR-TB patients using standardized versus individualized regimens in Brazil, a high TB-burden, low resistance setting. METHODS: The 2007-2013 cohort of the national electronic database (SITE-TB), which records all special treatments including drug-resistance, was analysed. Patients classified as MDR-TB in SITE-TB were eligible. Treatment outcomes were classified as successful (cure/treatment completed) or unsuccessful (failure/relapse/death/loss to follow-up). The odds for successful treatment according to type of regimen were controlled for demographic and clinical variables. RESULTS: Out of 4029 registered patients, we included 1972 recorded from 2010 to 2012, who had more complete outcome data. The overall success proportion was 60%. Success was more likely in non-HIV patients, sputum-negative at baseline, with unilateral disease and without prior DR-TB. Adjusted for these variables, those receiving standardized regimens had 2.7-fold odds of success compared to those receiving individualized treatments when failure/relapse were considered, and 1.4-fold odds of success when death was included as an unsuccessful outcome. When loss to follow-up was added, no difference between types of treatment was observed. Patients who used levofloxacin instead of ofloxacin had 1.5-fold odds of success. CONCLUSION: In this large cohort of MDR-TB patients with a low proportion of successful outcomes, standardized regimens had superior efficacy than individualized regimens, when adjusted for relevant variables. In addition to the limitations of any retrospective observational study, database quality hampered the analyses. Also, decision on the use of standard or individualized regimens was possibly not random, and may have introduced bias. Efforts were made to reduce classification bias and confounding. Until higher-quality evidence is produced, and DST becomes widely available in the country, our findings support the Brazilian recommendation for the use of standardized instead of individualized regimens for MDR-TB, preferably containing levofloxacin. Better quality surveillance data and DST availability across the country are necessary to improve MDR-TB control in Brazil.

Asunto(s)

Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Brasil , Estudios de Cohortes , Femenino , Humanos , Levofloxacino/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Esputo/microbiología , Resultado del Tratamiento

RESUMEN

Abstract Background: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. Methods: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. Results: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15–19 (OR = 2.86; 95% CI: 2.09–3.91) and 20–39 years old (OR = 2.30; 95% CI: 1.81–2.92) were more likely to default on TB treatment than those aged 0–14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR = 2.22; 95% CI: 1.43–3.44) or other causes (OR = 2.86; 95% CI: 2.14–3.83). Black patients were more likely to default on TB treatment (OR = 1.33; 95% CI: 1.22–1.44) and die from TB (OR = 1.50; 95% CI: 1.29–1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR = 1.94; 95% CI: 1.73–2.17), death due to TB (OR = 1.46; 95% CI: 1.25–1.71), death due to other causes (OR = 1.38; 95% CI: 1.21–1.57) and MDR-TB (OR = 2.29; 95% CI: 1.46–3.58). Conclusions: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Asunto(s)

Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Infecciones por VIH/complicaciones , Antituberculosos/uso terapéutico , Factores Socioeconómicos , Tuberculosis/epidemiología , Brasil/epidemiología , Infecciones por VIH/epidemiología , Estudios Transversales , Insuficiencia del Tratamiento , Notificación de Enfermedades , Coinfección

RESUMEN

BACKGROUND: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. METHODS: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. RESULTS: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15-19 (OR=2.86; 95% CI: 2.09-3.91) and 20-39 years old (OR=2.30; 95% CI: 1.81-2.92) were more likely to default on TB treatment than those aged 0-14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR=2.22; 95% CI: 1.43-3.44) or other causes (OR=2.86; 95% CI: 2.14-3.83). Black patients were more likely to default on TB treatment (OR=1.33; 95% CI: 1.22-1.44) and die from TB (OR=1.50; 95% CI: 1.29-1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR=1.94; 95% CI: 1.73-2.17), death due to TB (OR=1.46; 95% CI: 1.25-1.71), death due to other causes (OR=1.38; 95% CI: 1.21-1.57) and MDR-TB (OR=2.29; 95% CI: 1.46-3.58). CONCLUSIONS: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Asunto(s)

Antituberculosos/uso terapéutico , Infecciones por VIH/complicaciones , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Coinfección , Estudios Transversales , Notificación de Enfermedades , Femenino , Infecciones por VIH/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Insuficiencia del Tratamiento , Tuberculosis/epidemiología , Adulto Joven

RESUMEN

BACKGROUND: Despite the efforts of the National Tuberculosis Programme, TB cure rates in Brazil are sub-optimal. The End TB Strategy for post-2015 identifies conditional cash transfer interventions as powerful tools to improve TB control indicators, including TB cure rate. This study aims to inform the new policy by evaluating the role of the Bolsa Familia Programme (BFP), one of the largest conditional cash transfer programmes in the world, on TB cure rates in Brazil. METHODS: We undertook a retrospective cohort study, based on an unprecedented record linkage of socioeconomic and health data, to compare cases of patients newly diagnosed with TB in 2010 receiving BFP cash benefits (n=5788) with those who did not (n=1467) during TB treatment. We used Poisson regression with robust variance to estimate the relative risks for TB cure adjusted for known confounders. RESULTS: The cure rate among patients exposed to BFP during TB treatment was 82.1% (4752/5788), 5.2% higher than among those not exposed. This was confirmed after controlling for TB type, diabetes mellitus, HIV status and other relevant clinical and socioeconomic covariates (RR=1.07, 95% CI 1.04 to 1.11 for cure rates among BFP beneficiaries). This association seemed higher for patients not under directly observed treatment (RR=1.11; 95% CI 1.05 to 1.16). CONCLUSIONS: Although further research is needed, this study suggests that conditional cash transfer programmes can contribute to improve TB cure rate in Brazil.

Asunto(s)

Financiación de la Atención de la Salud , Asistencia Pública , Tuberculosis Pulmonar/prevención & control , Adolescente , Adulto , Brasil , Niño , Femenino , Programas de Gobierno , Humanos , Masculino , Registro Médico Coordinado , Persona de Mediana Edad , Áreas de Pobreza , Análisis de Regresión , Estudios Retrospectivos , Factores Socioeconómicos , Tuberculosis Pulmonar/terapia , Adulto Joven

RESUMEN

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 µg/mL and 8-16 µg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

Asunto(s)

Antifúngicos/farmacología , Candida/efectos de los fármacos , Hidrazonas/farmacología , Trichosporon/efectos de los fármacos , Antifúngicos/síntesis química , Antifúngicos/química , Benzaldehídos/farmacología , Candida/patogenicidad , Candidiasis/tratamiento farmacológico , Ácidos Carboxílicos/farmacología , Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Pared Celular/efectos de los fármacos , Hidrazinas/farmacología , Hidrazonas/síntesis química , Hidrazonas/química , Leucocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Piridinas/farmacología , Trichosporon/patogenicidad , Tricosporonosis/tratamiento farmacológico

RESUMEN

Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure-activity relationship (Q-SAR) studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87) affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05). The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (-77.8 ± 8.5, p < 0.001) against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize.

RESUMEN

BACKGROUND: The impact of non-communicable diseases on tuberculosis incidence has received significant attention. It has been suggested that the risk of tuberculosis is higher among subjects with diabetes and these subjects also has poor TB treatment outcomes.This study was aimed at assessing the socio-demographic and clinical factors that may influence different outcome of TB in patients with DM (TB-DM) identified in the Brazilian national database from 2001 to 2011. METHODS: TB-DM cases reported in the Brazilian information system were identified and compared.Covariates associated with the outcomes of interest (cure, default, deaths, and development of TB MDR) were included in a hierarchical regression model. RESULTS: TB-DM cases increased from 380/100,000/year in 2001 to 6,150/100,000/year in 2011. Some of the main associations found are pointed. The odds of default was higher among those in the age group 20-39 years (OR = 2.07, 95%CI 1.32-3.24); alcoholics (OR = 2.17, 95%CI 1.86-2.54), and HIV/AIDS (OR = 2.16, 95%CI 1.70-2.74);positive monitoring smear (OR = 1.94, 95%CI 1.55-2.43); prior default (OR = 5.41, 95%CI 4.47-6.54), and unknown type of treatment (OR = 3.33, 95%CI 1.54-7.22). The odds of death was greater for subjects ≥60 years old (OR = 2.74, 95%CI 1.74-4.29); institutionalized in shelter (OR = 2.69, 95%CI 1.07-6.77); alcoholics (OR = 2.70, 95%CI 2.27-3.22); HIV/AIDS (OR = 2.87, 95%CI 2.13-3.86); pulmonary+extrapulmonary TB (OR = 2.49, 95%CI 1.79-3.46); with unknown type of treatment (OR = 14.12, 95%CI 7.04-28.32).Development of MDR TB was more related to relapse (OR = 9.60, 95%CI 6.07-15.14);previous default (OR = 17.13, 95%CI 9.58-30.63); and transfer of treatment center (OR = 7.87, 95%CI 4.74-13.07). CONCLUSIONS: Older subjects and those with comorbidities and with a previous treatment of TB had poorest outcomes. TB control program in Brazil will need to expand efforts to focus on treatment of TB-DM patients to improve their cure rates in order to achieve the goals of tuberculosis elimination.

Asunto(s)

Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/terapia , Monitoreo Epidemiológico , Tuberculosis/epidemiología , Tuberculosis/terapia , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Complicaciones de la Diabetes/tratamiento farmacológico , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Análisis de Regresión , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Adulto Joven

RESUMEN

BACKGROUND: Over the last decade tuberculosis (TB) incidence and mortality in Brazil have been steadily declining. However, this downward trend has not been observed among HIV-infected patients. We describe the epidemiological and clinical profile of TB patients by HIV status using the Brazilian National Surveillance System. METHODS: All TB diagnoses with HIV status information between January 1, 2007 and December 31, 2011 were categorized as either HIV or non-HIV at time of TB diagnosis. Co-infected patients (TB-HIV) were compared to TB patients with no HIV-infection using a hierarchical logistic regression model using Stata 13.0. RESULTS: The prevalence of TB-HIV co-infection was 19% among adults ≥ 15 years of age. We analyzed data from 243,676 individuals, of whom 46,466 were TB-HIV and 197,210 were only TB cases. The following factors increased risk of co-infection: male sex (OR: 1.06, 95% CI 1.03-1.10), 20 to 39 years of age (OR = 4.82, 95% CI 4.34-5.36), black (OR = 1.08, 95% CI 1.04-1.13), 4-7 years of education (OR = 1.13, 95% CI 1.19-1.28), diagnosed following default (OR = 2.65, 95% CI 1.13-6.25), presenting with pulmonary and extra-pulmonary forms of TB simultaneously (OR = 2.80, 95% CI 1.56-5.02), presenting with histopathologic examination suggestive of TB (OR = 2.15, 95% CI 1.13-4.07). Co-infected patients were less likely to live in rural areas (OR = 0.45, 95% CI 0.42-0.48), have diabetes (OR = 0.45, 95% CI 0.40-0.50) and be smear positive (OR = 0.55, 95% CI 0.32-0.95), and co-infected patients had higher risk of default (OR = 2.96, 95% CI 2.36-3.71) and death from TB (OR = 5.16, 95% CI 43.04-5.77). CONCLUSIONS: The prevalence of co-infection with HIV among TB patients is 19% in Brazil. By identifying predictors of co-infection targeted interventions can be developed to prevent both TB and HIV, and to diagnose each disease earlier and ultimately decrease poor treatment outcomes and death.

Asunto(s)

Coinfección/epidemiología , Infecciones por VIH/epidemiología , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Coinfección/microbiología , Coinfección/virología , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Factores de Riesgo , Tuberculosis/complicaciones , Tuberculosis/microbiología , Adulto Joven

RESUMEN

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non-toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene-isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16-32 µg/mL and 4-16 µg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 µg/mL and 8 to 128 µg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.

Asunto(s)

Antifúngicos/síntesis química , Antifúngicos/farmacología , Triterpenos/química , Triterpenos/farmacología , Levaduras/efectos de los fármacos , Antifúngicos/química , Arthrodermataceae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Triterpenos Pentacíclicos , Triterpenos/síntesis química , Ácido Betulínico , Ácido Ursólico

RESUMEN

BACKGROUND: Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM. METHODS: Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients. RESULTS: Subjects with TB - DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26-1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03-2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60-0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51-0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51-0.86). CONCLUSIONS: Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.

Asunto(s)

Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Vigilancia de la Población , Factores Socioeconómicos , Resultado del Tratamiento , Tuberculosis/diagnóstico , Tuberculosis/terapia , Adulto Joven

RESUMEN

The chemical composition of the leaf oils of five Juniperus species (Juniperus sabina L., Juniperus communis Lam., Juniperus scopulorum Sarg., Juniperus virginiana L., Juniperus chinensis L., Cupressaceae) was determined by co-chromatography with authentic samples, GC-MS and Kováts retention indices. Sabinene was the most abundant component in the oils of Juniperus from western Patagonia Argentina. However, limonene and germacrene B constituted 25.1 percent and 11.5 percent of the oil of J. sabina. J. virginiana showed high concentration of alpha-humulene and limonene (31.4 and 15.9 percent respectively), while isobornyl acetate and germacrene B were also the main compounds of J. chinensis. Essential oils extracted of Juniperus were evaluated in vitro for their efficacy against Fusarium verticillioides, Aspergillus flavus, Aspergillus parasiticus, Candida albicans and Rhodotorula infection. Candida albicans was not inhibited for the essential oils of Juniperus. However, F. verticillioides, A. flavus, A. parasiticus and Rhodotorula were inhibited for these oils.

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La composición de los aceites esenciales de la hoja de cinco especies de Juniperus (Juniperus sabina L., Juniperus communis Lam., Juniperus scopulorum Sarg., Juniperus virginiana L., Juniperus chinensis L., Cupressaceae), se determinó mediante una co-cromatografía con muestras auténticas de dos columnas de diferente polaridad, CG-EM y los índices de retención de Kovats. El sabineno fue el componente más abundante en los aceites de Juniperus del oeste de la Patagonia Argentina. Sin embargo, el limoneno y el germacreno B son otros componentes importantes del aceite esencial de J. sabina con el 25,1 por ciento y 11,5 por ciento respectivamente. En J. virginiana el alfa-humuleno y el limoneno (con el 31,4 por ciento y 15.9 por ciento respectivamente) mostraron ser también importantes, mientras que el acetato de isobornilo y el germacreno B fueron también los principales componentes de la J. chinensis. Los aceites esenciales extraídos de Juniperus se evaluaron in vitro para determinar su eficacia contra Fusarium verticillioides, Aspergillus flavus, Aspergillus parasiticus, Candida albicans y Rhodotorula. Candida albicans no se inhibió por la acción de los aceites esenciales de Juniperus. Sin embargo, F. verticillioides, A. flavus, A. parasiticus y Rhodotorula fueron inhibidos.

Asunto(s)

Aceites Volátiles/farmacología , Antifúngicos/farmacología , Hongos Mitospóricos , Juniperus/química , Argentina , Aceites Volátiles/química , Hongos Mitospóricos/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana