Leishmania isoenzyme polymorphisms in Ecuador: Relationships with geographic distribution and clinical presentation

Background: Determinants of the clinical presentation of the leishmaniases are poorly understood but Leishmania species and strain differences are important. To examine the relationship between clinical presentation, species and isoenzyme polymorphisms, 56 Leishmania isolates from distinct presentations of American tegumentary leishmaniasis (ATL) from Ecuador were analyzed. Methods: Isolates were characterized by multilocus enzyme electrophoresis for polymorphisms of 11 isoenzymes. Patients were infected in four different ecologic regions: highland and lowland jungle of the Pacific coast, Amazonian lowlands and Andean highlands. Results: Six Leishmania species constituting 21 zymodemes were identified: L. (Viannia) panamensis (21 isolates, 7 zymodemes), L. (V.) guyanensis (7 isolates, 4 zymodemes), L. (V.) braziliensis (5 isolates, 3 zymodemes), L. (Leishmania) mexicana (11 isolates, 4 zymodemes), L. (L.) amazonensis (10 isolates, 2 zymodemes) and L. (L.) major (2 isolates, 1 zymodeme). L. panamensis was the species most frequently identified in the Pacific region and was associated with several clinical variants of cutaneous disease (CL); eight cases of leishmaniasis recidiva cutis (LRC) found in the Pacific highlands were associated with 3 zymodemes of this species. Mucocutaneous leishmaniasis found only in the Amazonian focus was associated with 3 zymodemes of L. braziliensis. The papular variant of CL, Uta, found in the Andean highlands was related predominantly with a single zymodeme of L. mexicana. Conclusion: Our data show a high degree of phenotypic variation within species, and some evidence for associations between specific variants of ATL (i.e. Uta and LRC) and specific Leishmania zymodemes. This study further defines the geographic distribution of Leishmania species and clinical variants of ATL in Ecuador

Cerebral White Matter and Retinal Arterial Health in Hypertension and Type 2 Diabetes Mellitus

We examined 33 hypertensive (22 with comorbid type 2 diabetes mellitus (T2DM)) and 29 normotensive (8 with T2DM) middle-aged and elderly adults, comparable in age and education. Relative to normotensive participants, those with hypertension, in addition to a higher prevalence of periventricular white matter (WM) lesions, had significantly lower WM microstructural integrity of major fiber tracts as seen with MRI-based diffusion tensor imaging. Among participants with hypertension, those with co-morbid T2DM (n=22) had more widespread WM pathology than those without T2DM (n=11). Furthermore and consistent with previous research, both hypertension and T2DM were related to decreased retinal arterial diameter. Further exploratory analysis demonstrated that the observed retinal arteriolar narrowing among individual with hypertension was associated with widespread subclinical losses in WM microstructural integrity and these associations were present predominantly in the frontal lobe. We found that T2DM adds to the damaging effects of hypertension on cerebral WM, and notably these effects were independent of age and body mass index. Given that the decrease in retinal arteriolar diameter may be a biomarker for parallel pathology in cerebral arterioles, our data suggest that the frontal lobe may be particularly vulnerable to microvascular damage in the presence of hypertension and T2DM

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

Use of Buffers in Specific Contexts : Highly Trained Female Athletes, Extreme Environments and Combined Buffering Agents - A Narrative Review

This narrative review evaluated the evidence for buffering agents (sodium bicarbonate, sodium citrate and beta-alanine), with specific consideration of three discrete scenarios: female athletes, extreme environments and combined buffering agents. Studies were screened according to exclusion and inclusion criteria and were analysed on three levels: (1) moderating variables (supplement dose and timing, and exercise test duration and intensity), (2) design factors (e.g., use of crossover or matched group study design, familiarisation trials) and (3) athlete-specific factors (recruitment of highly trained participants, buffering capacity and reported performance improvements). Only 19% of the included studies for the three buffering agents reported a performance benefit, and only 10% recruited highly trained athletes. This low transferability of research findings to athletes’ real-world practices may be due to factors including the small number of sodium citrate studies in females (n = 2), no studies controlling for the menstrual cycle (MC) or menstrual status using methods described in recently established frameworks, and the limited number of beta-alanine studies using performance tests replicating real-world performance efforts (n = 3). We recommend further research into buffering agents in highly trained female athletes that control or account for the MC, studies that replicate the demands of athletes’ heat and altitude camps, and investigations of highly trained athletes’ use of combined buffering agents. In a practical context, we recommend developing evidence-based buffering protocols for individual athletes which feature co-supplementation with other evidence-based products, reduce the likelihood of side-effects, and optimise key moderating factors: supplement dose and timing, and exercise duration and intensity

Методология синтеза архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки

Предложен подход к проектированию архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки в реальном времени, основанный на классификации решаемых функциональных задач на основе методов кластерного анализа и выбранного множества признаков подобия. Разработанный подход позволяет из множества функций системы выделить подобные (по определенным признакам) и объединить их в архитектурные компоненты (унифицированные функциональные модули).Запропоновано підхід до проектування архітектури центру обробки інформації автоматизованої системи моніторингу середовища в реальному часі, що заснований на класифікації функціональних задач на підставі методів кластерного аналізу і обраної множини ознак схожості. Розроблений підхід дозволяє вибрати із множини функцій системи схожі (за певними ознаками) і поєднати їх в архітектурні компоненти (уніфіковані функціональні модулі).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)

Auditing the Representation of Females Versus Males in Heat Adaptation Research

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18–50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions

Estructuración de una colonia de ratones BALB/c en la Unidad Experimental de Inmunoterapia de la Fundación Jacinto Convit – Venezuela

Animal models are a fundamental part of preclinical scientific research in the development of new therapies including drugs and gene therapies. For such purposes, it is crucial to have an animal model that is appropriate for specific study. At the animal facility of the Unidad Experimental de Inmunoterapia (UEI) of Fundación Jacinto Convit (FJC), a colony of BALB/c mice was established to maintain a pure strain for experimental research projects in breast cancer, using the 4T1 autologous tumor cell line. The colony was established from two pairs of BALB/c mice provided by Universidad Simón Bolívar, ensuring strict housing conditions in micro-isolators, with appropriate feeding, environmental enrichment, and detailed control of both micro and macroenvironment parameters required for the species. Animals care was managed by a specialized biologist. The expansion of this BALB/c mouse strain was monitored following a pattern of inbred crosses every third litter. Homozygosity was determined by using skin grafting technique among individuals of the same strain and comparative microsatellite analysis. Data from 135 births were analyzed, with a maximum of 6 births per breeding box. Monogamous pairs produced an average of 6.25 ± 2.38 pups per litter, with no unexpected deaths, and an interbirth interval of 27 ± 7.5 days. The overall results obtained in this work demonstrated that the breeding, care, and maintenance protocol of the BALB/c mouse colony at the UEI animal facility of FJC is effective in ensuring the expansion and genetic purity of this strain, hereafter referred to as BALB/c//USB//FJC.Los modelos animales son parte fundamental de la investigación científica preclínica en el desarrollo de nuevas terapias, incluyendo drogas y terapias génicas. Para tales fines, es crucial contar con un modelo animal acorde con el estudio a realizar. En el bioterio de la Unidad Experimental de Inmunoterapia (UEI) de la Fundación Jacinto Convit (FJC) se estructuró una colonia de ratones BALB/c a fin de contar con una cepa pura para llevar a cabo proyectos de investigación experimental en cáncer de mama, utilizando la línea de células de tumor autólogo 4T1. Esta colonia se estableció a partir de dos parejas de ratones BALB/c proporcionados por la Universidad Simón Bolívar, asegurando condiciones estrictas de alojamiento en microaisladores, con alimentación adecuada, enriquecimiento ambiental y control detallado del micro y macroambiente requerido para la especie. El cuidado de los animales estuvo a cargo de un biólogo especializado. La expansión de esta cepa de ratones BALB/c se evaluó siguiendo un esquema de cruces endogámicos programados en cada tercer parto. La homocigosidad se determinó mediante la técnica de injerto de piel entre individuos de la misma cepa y el análisis comparativo de microsatélites. Se analizaron los datos obtenidos de 135 partos, con un máximo de 6 partos por caja reproductora, provenientes de parejas monógamas donde no ocurrieron muertes inesperadas y se obtuvo en promedio de 6,25 ± 2,38 crías por parto, y un periodo interparto de 27 ± 7,5 días. El conjunto de los resultados obtenidos en este trabajo demostró que el protocolo de reproducción, cuidado y mantenimiento de la colonia de ratones BALB/c en el bioterio de la UEI de la FJC, es eficaz para garantizar la expansión y pureza genética de esta cepa, en adelante denominada BALB/c//USB//FJC

Predicting Future Clinical Changes of MCI Patients Using Longitudinal and Multimodal Biomarkers

Accurate prediction of clinical changes of mild cognitive impairment (MCI) patients, including both qualitative change (i.e., conversion to Alzheimer's disease (AD)) and quantitative change (i.e., cognitive scores) at future time points, is important for early diagnosis of AD and for monitoring the disease progression. In this paper, we propose to predict future clinical changes of MCI patients by using both baseline and longitudinal multimodality data. To do this, we first develop a longitudinal feature selection method to jointly select brain regions across multiple time points for each modality. Specifically, for each time point, we train a sparse linear regression model by using the imaging data and the corresponding clinical scores, with an extra ‘group regularization’ to group the weights corresponding to the same brain region across multiple time points together and to allow for selection of brain regions based on the strength of multiple time points jointly. Then, to further reflect the longitudinal changes on the selected brain regions, we extract a set of longitudinal features from the original baseline and longitudinal data. Finally, we combine all features on the selected brain regions, from different modalities, for prediction by using our previously proposed multi-kernel SVM. We validate our method on 88 ADNI MCI subjects, with both MRI and FDG-PET data and the corresponding clinical scores (i.e., MMSE and ADAS-Cog) at 5 different time points. We first predict the clinical scores (MMSE and ADAS-Cog) at 24-month by using the multimodality data at previous time points, and then predict the conversion of MCI to AD by using the multimodality data at time points which are at least 6-month ahead of the conversion. The results on both sets of experiments show that our proposed method can achieve better performance in predicting future clinical changes of MCI patients than the conventional methods