RESUMO
Isothermal amplification of nucleic acids has the potential to be applied in resource-limited areas for the detection of infectious agents, as it does not require complex nucleic purification steps or specific and expensive equipment and reagents to perform the reaction and read the result. Since human and animal infections by pathogens of the Tryponasomatidae family occur mainly in resource-limited areas with scant health infrastructures and personnel, detecting infections by these methodologies would hold great promise. Here, we conduct a narrative review of the literature on the application of isothermal nucleic acid amplification for Trypanosoma and Leishmania infections, which are a scourge for human health and food security. We highlight gaps and propose ways to improve them to translate these powerful technologies into real-world field applications for neglected human and animal diseases caused by Trypanosomatidae.
Assuntos
Leishmaniose , Ácidos Nucleicos , Parasitos , Trypanosomatina , Animais , Humanos , Leishmaniose/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Ácidos Nucleicos/genéticaRESUMO
Campylobacter jejuni is the leading cause of bacterial food-borne gastroenteritis worldwide and human infections are frequently associated with handling and consumption of contaminated poultry. The polysaccharide capsule of C. jejuni plays important roles in colonisation of the chicken gut, invasion of epithelial cells and serum resistance and is subject to modification with O-methyl phosphoramidate (MeOPN) in most strains. In this study, the cytokine responses of mouse bone marrow-derived macrophages (mBMMs), chicken bone marrow-derived macrophages (chBMMs) and human monocyte-derived macrophages (hMDMs) were measured following infection with C. jejuni 11168H wild-type (WT) or isogenic mutants lacking either the capsule (Δcj1439) or its MeOPN modification (Δcj1417). Consistent with previous observations using murine bone marrow-derived dendritic cells, mutants lacking the capsule or MeOPN elicited enhanced transcription of IL-6 and IL-10 in mBMMs compared to wild-type C. jejuni. However, the lack of capsule and MeOPN did not alter IL-6 and IL-10 expression in chBMMs and hMDMs compared to C. jejuni WT. Phagocytosis assays showed the acapsular mutant was not impaired in uptake or net intracellular survival after phagocytosis in both chicken and human macrophages; however, the phagocytosis of the MeOPN mutant was significantly decreased in both chicken and human macrophages. In conclusion, differences in the response of macrophages of varying host origin to Campylobacter were detected. The absence of MeOPN modification on the capsule of C. jejuni did not alter the levels of innate cytokine expression in both chicken and human macrophages compared to the 11168H WT, but affected phagocytosis by host macrophages.
Assuntos
Infecções por Campylobacter/veterinária , Campylobacter jejuni/fisiologia , Galinhas , Macrófagos/metabolismo , Doenças das Aves Domésticas/microbiologia , Amidas/metabolismo , Animais , Cápsulas Bacterianas/metabolismo , Medula Óssea , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/genética , Citocinas/metabolismo , Humanos , Monócitos/metabolismo , Mutação , Ácidos Fosfóricos/metabolismo , RatosRESUMO
Introduction: Stroke is the second most common cause of death and disability-adjusted life years (DALYs) globally. However, the incidence and impact of stroke by ethnicity and gender is frequently distinct. This is particularly the case in Ecuador where geographic and economic marginalization are often correlated with ethnic marginalization and the extent to which females lack the same opportunities as their male counterparts. The aim of this paper is to investigate the differential impacts in terms of stroke diagnosis and burden of disease by ethnicity and gender, using hospital discharge records over the years 2015-2020. Methods: This paper calculates stroke incidence, and fatality rates using hospital discharge and death records over the years 2015-2020. The DALY package in R was employed to calculate the Disability Adjusted Life Years lost due to stroke in Ecuador. Results: The results show that while the incidence rate of stroke in males (64.96 per 100,000 persons-year) is higher than that for females on average (57.84 per 100,000 persons-year), males accounted for 52.41% of all stroke cases and 53% of all surviving cases. Thus, hospital data suggests that females had a higher death rate when compared to males. Case fatality rates also differed significantly by ethnicity. The highest fatality rate corresponded to the Montubio ethnic group (87.65%), followed by Afrodescendants (67.21%). The estimated burden of disease of stroke calculated using Ecuadorian hospital records (2015-2020) varied from 1,468 to 2,991 DALY per 1,000 population on average. Discussion: Differences in the burden of disease by ethnic group are likely to reflect differential access to care by region and socio-economic group, both of which are frequently correlated with ethnic composition in Ecuador. Equitable access to health services remains an important challenge in the country. The gender discrepancy in fatality rates suggests that there is a need for targeted educational campaigns to identify stroke signs early, especially in the female population.
RESUMO
BACKGROUND: Chagas disease, a neglected tropical disease endemic to Latin America caused by the parasite Trypanosoma cruzi, currently affects 6-7 million people and is responsible for 12,500 deaths each year. No vaccine exists at present and the only two drugs currently approved for the treatment (benznidazole and nifurtimox), possess serious limitations, including long treatment regimes, undesirable side effects, and frequent clinical failures. A link between parasite genetic variability and drug sensibility/efficacy has been suggested, but remains unclear. Therefore, we investigated associations between T. cruzi genetic variability and in vitro benznidazole susceptibility via a systematic article review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: In vitro normalized benznidazole susceptibility indices (LC50 and IC50) for epimastigote, trypomastigote and amastigote stages of different T. cruzi strains were recorded from articles in the scientific literature. A total of 60 articles, which include 189 assays, met the selection criteria for the meta-analysis. Mean values for each discrete typing unit (DTU) were estimated using the meta and metaphor packages through R software, and presented in a rainforest plot. Subsequently, a meta-regression analysis was performed to determine differences between estimated mean values by DTU/parasite stage/drug incubation times. For each parasite stage, some DTU mean values were significantly different, e.g. at 24h of drug incubation, a lower sensitivity to benznidazole of TcI vs. TcII trypomastigotes was noteworthy. Nevertheless, funnel plots detected high heterogeneity of the data within each DTU and even for a single strain. CONCLUSIONS/SIGNIFICANCE: Several limitations of the study prevent assigning DTUs to different in vitro benznidazole sensitivity groups; however, ignoring the parasite's genetic variability during drug development and evaluation would not be advisable. Our findings highlight the need for establishment of uniform experimental conditions as well as a screening of different DTUs during the optimization of new drug candidates for Chagas disease treatment.
Assuntos
Nitroimidazóis/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Resistência a Medicamentos , Variação Genética , Humanos , Trypanosoma cruzi/genéticaRESUMO
The title salt, C(21)H(27)N(2) (+)·Cl(-) resulted from the condensation between 2,6-dimethyl-aniline and acetyl-acetone in acidified ethanol. The bulky cation is stabilized in a ß-imino-enamine tautomeric form, and presents a W-shaped conformation. The benzene rings are arranged almost parallel, with a dihedral angle of 6.58â (4)° between the mean planes. Both N-H groups in the cation form strong hydrogen bonds with two symmetry-related chloride anions. The resulting supra-molecular structure is a one dimensional polymer running along [001], alternating cations and anions. The π-π inter-action observed in the mol-ecule, characterized by a centroid-centroid separation of 4.298â (4)â Å, is thus extended to the chains, with separations of 5.222â (4)â Å between benzene rings of neighbouring cations in the crystal.
RESUMO
We ascertain the in vitro Benznidazole (BZN) and Nifurtimox (NFX) susceptibility pattern of epimastigotes, trypomastigotes, and amastigotes of 21 T. cruzi strains, from patients, reservoir, and triatomine bugs of various geographic origins. Using this panel of isolates, we compute the Epidemiological cut off value (COwt). Then, the frequency of the susceptible phenotype (Wild type) towards benznidazole (BZN) and nifurtimox (NFX) within this set of strains belonging to three discrete typing units (DTUs), TcI, TcII, and TcV, was deduced. We observed that the susceptibility status of individual T. cruzi isolates toward BZN and NFX is related to the genetic background and underlying factors that are probably related to the individual life trait history of each strain. Analyzing drug susceptibility in this conceptual framework would offer the possibility to evidence a link between isolates expressing a low susceptibility level (not wild-type) as defined by the COwt value and none-curative treatment. It will also permit us to track drug-resistant parasites in the T. cruzi population.
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Este estudio exploró la correlación entre el bienestar subjetivo y la imagen corporal de las estudiantes mujeres en una universidad de Arequipa. La muestra estuvo constituida de 155 estudiantes mujeres entre los 17 y 24 años de las tres carreras profesionales. Las participantes fueron evaluadas en sus respectivos salones. La validación del Cuestionario de la Imagen Corporal (BSQ) fue calculada con Alfa de Cronbach y se obtuvo un valor de 0.92. Los resultados indicaron que existe una correlación negativa significativa entre el bienestar subjetivo y la imagen corporal (r = -0.478; p < 0.001). Asimismo, se indicó que no existe diferencia estadísticamente significativa entre las carreras de administración y derecho con respecto al bienestar subjetivo (t = 0.201; p > 0.05) y a la imagen corporal (t = -0.606; p > 0.05). Esto muestra que la distorsión de la imagen corporal tiene un impacto negativo en el bienestar subjetivo de las estudiantes universitarias mujeres.
This study explored the correlation between subjective wellbeing and body image of female students at a university in Arequipa. The sample consisted by 155 female students between 17 and 24 years old from the three professional careers. The participants were evaluated in their respective classrooms. The validation of the Body Shape Questionnaire (BSQ) was calculated using CronbachÆs alpha and obtained a value of 0.92. The results indicated that there is significant negative correlation between the subjective wellbeing and body image (r = -0.478; p < 0.001). It was also noted that there is no statistical significant difference between management and law careers with respect to the subjective wellbeing (t = 0.201; p > 0.05) and body image (t = -0.606; p > 0.05). This shows that the distortion of body image has a negative impact on the subjective wellbeing of women university students.