EXERT-BC: A pilot study of an exercise regimen designed to improve functional mobility, body composition, and strength after the treatment for breast cancer.

PURPOSE: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high-intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT-BC trial assesses the safety and feasibility of an evidence-based, dose-escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition. METHODS: Participants included women with breast cancer underwent a 3-month thrice weekly exercise regimen involving dose escalation of high-intensity compound exercises. Coprimary outcomes included safety and adherence. Pre- and post-regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test. RESULTS: Fourty participants completed a 3-month exercise regimen, with a median age of 57 years (range, 27-74 years) and 73% having stage 0-2 BC. BC therapies concurrent with exercise included anti-estrogen therapy (80%), radiotherapy (30%), and non-hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self-limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y-Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed. CONCLUSION: A 3-month dose-escalated resistance training regimen comprising high-intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient-reported quality of life.

EXERT-BC: Prospective Study of an Exercise Regimen After Treatment for Breast Cancer.

Purpose EXERT-BC is a dose-escalated resistance training regimen created to improve body composition, strength, and balance in women treated for breast cancer (BC). Herein, we report the interim analysis. Women treated for BC underwent this 3-month exercise regimen in an exercise oncology facility with continual monitoring of load and strength. Twenty women completed the IRB-approved protocol, with a mean age of 57 years (range 41-74). Concurrent therapies included anti-estrogen therapy (73%), chemotherapy (14%), and radiotherapy (23%). 27% of women endorsed prior exercise. Subjects missed an average of 1.75 classes (range 0-7), with all meeting adherence over 75%. No injuries or adverse events were reported aside from muscle soreness and 2 days of knee pain. Significant differences in body composition at completion included reduced body fat (38.2% vs. 36.7%, p=0.003), and increased muscle mass (33.1% vs. 37.1%, p<0.001), functional mobility screening (9.82 vs. 11.73, p=0.018), and Y-balance (left: 72.4 vs. 85.3, p=0.001; right: 70.3 vs. 85.2. p<0.001). Significant increases in load were demonstrated: split squat (p<0.001), trap bar deadlift (p=0.035), inclined dumbbell press (p<0.001), and bird dog rows (p<0.001). Dose-escalated resistance training in women with BC is safe and feasible, endorsing significant improvements across body composition, balance, and strength.

La tuberculosis en el municipio Marianao: tendencias en dos periodos recientes, 2001­2005 y 2015­2020 / Tuberculosis in the Marianao Municipality: Trends in Two Recent Periods, 2001-2005 and 2015-2020

Introducción: Marianao históricamente ha sido un municipio de La Habana con alta carga de tuberculosis. Una nueva mirada sería importante.

Introduction: Marianao has historically been a municipality of Havana with a high bur-den of tuberculosis. A new look would be important.

Electrical dataset of household appliances in operation in an apartment.

This data article presents electricity demand data on common household appliances in the Dominican Republic and therefore in the Caribbean region, as well as appliances whose demand characteristics are maintained regardless of geographic location. A one-hour record is made in most cases, for 17 household appliances, containing information on power demand, effective current, power factor and harmonic distortion of voltage and current. The average, minimum, and maximum values ​​of each parameter for one minute are provided. The data were obtained using the Fluke-1738 electrical network analyzer. The data can be used to build demand profiles in the residential or commercial sector, depending on the composition of electrical appliances and the hours of use, dimension photovoltaic systems for self-consumption and emergency electrical sources. Although the number of household appliances and conditions of use of some appliances do not constitute a representative sample, the dataset and the measurement method constitute a starting point for obtaining this type of records, which are scarce in the literature.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Alternativas de procesos para la búsqueda de casos de tuberculosis bajo condiciones económicas limitadas. Cuba 2022-2025 / Process Alternatives for the Tuberculosis Case Finding under Limited Economic Conditions. Cuba 2022-2025

Ejecutar procesos efectivos de búsqueda de casos de tuberculosis es crucial para acele-rar el paso hacia su eliminación. El empeoramiento de las condiciones económicas mun-diales y nacionales no nos permite aplicar extensivamente las tecnologías rápidas mo-leculares idóneas de diagnóstico. Consideramos sensato entonces aplicar algoritmos alternativos que satisfagan las necesidades nacionales presentes hasta que las condi-ciones permitan la cobertura completa de las tecnologías moleculares recomendadas. Sugerimos introducir la radiografía digital para todos los algoritmos, utilizar mejor la microscopía de fluorescencia LED y la óptica convencional ya probadas. En conclusión, es preciso que este enfoque de trabajo, que procura optimizar la efectividad y eficiencia del programa, se introduzca en la práctica cotidiana hasta que lo idóneo sea permisible

Executing effective tuberculosis case-finding processes is crucial to accelerate the path towards elimination of the disease. The worsening of global and national economic conditions do not allow us to extensively apply rapid molecular diagnostic technolo-gies. We consider it sensible and necessary to apply alternative algorithms that meet the current national needs, until conditions allow full coverage of the recommended molecular technologies. We suggest introducing digital X-rays for all algorithms, bet-ter use of LED fluorescence microscopy and conventional optics already appropriate-ly tested. In conclusion, it is necessary that this approach that seeks to optimize the effectiveness and efficiency of the Cuban program be introduced into daily practice until the ideal is permissible

Coinfection of Canine Distemper Virus and Rabies Virus in Wildlife Samples Submitted for Routine Rabies Testing.

Canine distemper virus (also known as Canine morbillivirus), the etiologic agent of canine distemper, is a highly contagious pathogen causing a multisystemic infection in carnivores globally. Canine distemper may be clinically indistinguishable from rabies, and outbreaks of either disease are major concerns. In the US, both diseases are endemic and managed by parenteral vaccination in domestic animals. In wildlife, oral vaccination and trap-vaccinate-release programs are available for rabies prevention, but no such strategies exist for canine distemper. We evaluated the prevalence at which canine distemper virus occurred concurrently in animals infected with rabies virus. Real-time quantitative reverse transcriptase PCR (qRT-PCR) was performed on specimens previously diagnosed with rabies during 2017-19 by the New York State Rabies Laboratory. Real-time qRT-PCR detected concurrent canine distemper virus infection in 73 of 1,302 animals with rabies virus. Coinfection rates were approximately 9% in Procyon lotor, 2% in Vulpes vulpes, and 0.4% in Mephitis mephitis, with an overall prevalence of 5.6%. As comorbidities in wildlife occur, laboratory-based surveillance and confirmatory testing are critical to rapid decision making for disease prevention. Rabies virus incursions are expensive and difficult to manage, and spillover events create health risks to humans and domestic animals as well as to free-roaming wildlife.

Desigualdades territoriales de la tuberculosis entre los municipios de La Habana, 2015 y 2016-2020 / Territorial Inequalities of Tuberculosis between the Municipalities of Havana, 2015 and 2016-2020

La Habana notifica el 30% de casos de tuberculosis (TB) en Cuba. Objetivo: valorar las desigualdades territoriales en la ocurrencia de TB en los municipios de La Habana, 2015 y 2016-2020 según algunos determinantes intermedios e individuales. Métodos: estudio ecológico de series temporales sobre las notificaciones de TB en 2015 y 2016-2020. La fuente fue la base de vigilancia del MINSAP. Calculamos la tasa del periodo (TP), la referencia fue la menor, estimamos las diferencias absolutas y relativas, y el Riesgo Atribuible Poblacional Porcentual. Estimamos la TP en menores y mayores de 19 años. Según la TP, propusimos dos escenarios: -reducción 5% anual a todos los municipios, según Hitos de OMS y -reducción discriminada 5% anual a municipios con TP < 9 y 7% los ≥ 9/100.000. Calculamos dos índices de dispersión y proporciones de TB en VIH y reclusos. Categorizamos los municipios según metas renovadas hacia la eliminación. Resultados: el municipio de referencia fue Playa (5,5), la diferencia relativa fue 3,3 veces más en Habana Vieja. Cotorro y Guanabacoa no aportaron casos pediátricos. El segundo escenario tuvo desigualdad moderada. Predominaron los TB-VIH, en Habana Vieja (13,1%). 11/15 municipios categorizaron en control satisfactorio. Conclusiones: las desigualdades en general son moderadas en los municipios Habana, no obstante, las tasas de TB infantil son muy bajas en los territorios, dos de ellos alcanzaron la meta de eliminación. La coinfección TB/VIH concentra las mayores proporciones en algunos municipios. (AU);

Havana notifies 30% of cases of tuberculosis (TB) in Cuba. Objective: to assess the territorial inequalities in the occurrence of TB in the municipalities of Havana, 2015 and 2016-2020 according to some intermediate and individual determinants. Methods: ecological study of time series on TB notifications in 2015 and 2016-2020. The source was the MINSAP surveillance base. We calculated the period rate (TP), the reference was the lowest, we estimated the absolute and relative differences, and the Percentage Population Attributable Risk. We estimate the PT in children under and over 19 years of age. According to the TP, we proposed two scenarios: -5% annual reduction to all municipalities, according to WHO Milestones and -discriminated 5% annual reduction to municipalities with TP < 9 and 7% those ≥ 9/100,000. We calculated two dispersion indices and proportions of TB in HIV and inmates. We categorized the municipalities according to renewed goals towards elimination. Results: the reference municipality was Playa (5.5), the relative difference was 3.3 times more in Habana Vieja. Cotorro and Guanabacoa did not provide pediatric cases. The second scenario had moderate inequality. TB-HIV predominated in Old Havana (13.1%). 11/15 municipalities categorized in satisfactory control. Conclusions: inequalities were generally moderate in the Havana municipalities, however, the rates of childhood TB are very low in the territories, two of them reached the elimination goal. TB/HIV coinfection concentrates the highest proportions in some municipalities. (AU)

Tuning of Cu-Al Interactions in Complexes Derived from Tris(pyridonyl-6-methyl)aluminum Metalloligands.

A series of bioinspired polar atrane Cu-Al complexes were studied with a combined experimental and computational approach to assess the range and nature of Cu-Al interactions in these novel species. The aluminum metalloligand [Na{Me2Al(OPy-6-Me)2}] (2) was furnished in excellent yield (92%) from the nucleophilic attack of Na(OPy-6-Me) to AlMe3 and the subsequent alkane elimination reaction with 6-methyl-2-hydroxypyridine. At the same time, the metalloligand [Al(OPy-6-Me)3] (3) was isolated in an also excellent yield (95%) via alkane elimination of AlMe3 with 6-methyl-2-hydroxypyridine. The zwitterionic Cu-Al atranes [Cu{MeAl(OPy-6-Me)3}] (5Me) and [Cu{MesAl(OPy-6-Me)3}] (5Mes) were isolated (73 and 97% yields) from metalloligands 2 and 3, respectively. [(Cu{Al(OPy-6-Me)4})2(µ-Cu)]+ ([6+][B(ArCF3)4]) was isolated via a reaction that involves alkane elimination and redistribution reacting from 5Me with [H(OEt2)2][B(ArCF3)4] in benzene solution. Alkane elimination in benzene of either 5Me or 5Mes with [HNEt3][B(ArCF3)4] renders [Cu{(Et3N)Al(OPy-6-Me)3}]+ (Et3N-5+). The Lewis base-free cationic complex [Cu{Al(OPy-6-Me)3}]+ (5+) was isolated in 68% yield upon reacting 3 with [Cu(COD)2][B(ArCF3)4] in benzene. Metalloligands and complexes were fully characterized with an array of spectroscopic and analytical techniques that include multinuclear NMR, ATR-IR, ESI-spectrometry, combustion microanalysis, cyclic voltammetry (CV), and, whenever feasible, SCXRD. X-ray and DFT parameters indicate that the strength of the Cu→Al transannular interaction follows the trend 5+ > Et3N-5+ > [6+][B(ArCF3)4], 5Me, and 5Mes in a smooth transition from zwitterionic species where the Cu-Al interaction is nonexistent to moderate Cu-Al Z-type interactions. CV, in conjunction with DFT calculations of Et3N-5+ and 5+, hint at the generation in the electrochemical cell of the radical species 5rad at -1.82 V and the anionic complex 5- at -2.32 V vs Fc/Fc+, respectively. The proposed species 5rad exhibits 2-center/1-electron (2c/1e) σ bonding whereas 5- a 2-center/2-electron (2c/2e) bond.

Resistance Training for Patients with Cancer: A Conceptual Framework for Maximizing Strength, Power, Functional Mobility, and Body Composition to Optimize Health and Outcomes.

There are many benefits to the addition of exercise to cancer treatment and survivorship, particularly with resistance training regimens that target hypertrophy, bone mineral density, strength, functional mobility, and body composition. These goals are best achieved through a series of individualized high-intensity compound movements that mirror functional mobility patterns and sufficiently stress the musculoskeletal system. As a result of adequate stress, the body will engage compensatory cellular mechanisms that improve the structural integrity of bones and muscles, stimulate metabolism and the immune system, optimize functional performance, and minimize mechanical injury risk. The current evidence suggests that application of the above exercise principles, practiced in a safe environment under expert observation, may offer patients with cancer an effective means of improving overall health and cancer-specific outcomes. The following article poses several important questions certified exercise specialists and physicians should consider when prescribing resistance exercise for patients with cancer.

Modelo general de la determinación social de la salud para la tuberculosis

Introducción : El avance hacia la eliminación de la tuberculosis en Cuba, depende de la justicia social para las personas afectadas y sus familiares, barrio por barrio, área de salud por área de salud y municipio por municipio. Para potenciar las dimensiones de su determinación social será necesario un modelo de eliminación local asentado en su enfoque general. Objetivo : Describir un modelo general con enfoque sistémico de la determinación social en salud, aplicado a la tuberculosis. Métodos : Se realizó un estudio cualitativo basado en una revisión documental de artículos sobre la determinación social, con diseño de un modelo explicativo, simple para su comprensión, con componentes estructurales, intermedios e individuales para ser adaptado en el tema de la tuberculosis. Resultados : El modelo planteado tiene como entrada la voluntad política, dependiente del poder establecido que determina las políticas públicas, interactuando con las dimensiones intermedias como aspectos centrales y con las dimensiones individuales de carácter sociodemográficas, socioculturales y socioeconómicas. Estas a su vez retroalimentan e influyen nuevamente en la Voluntad política y las Políticas públicas, cerrando el ciclo sistémico. Además, se incluye el control interactivo del sistema. Conclusiones : Además de los modelos planteados en la literatura nacional revisada, abundar en su enfoque sistémico contribuye a facilitar la comprensión del monitoreo de la Determinación social de la tuberculosis por parte del personal encargado de dar sostenibilidad del control hacia la eliminación.

Introduction : Progress towards the tuberculosis elimination in Cuba depends on social justice for the people affected and their families, neighborhood by neighborhood, health area by health area and municipality by municipality. To enhance the dimensions of its social determination, a local elimination model based on its general approach will be necessary. Objective: To describe a general model with a systemic approach to Social determination in health, applied to tuberculosis. Methods : A qualitative study based on a documentary review of articles on social determination was carried out, with the design of an explanatory model, simple for its understanding, with structural, intermediate and individual components to be adapted to the topic of tuberculosis. Results : The proposed model has as input the political will, dependent on the established power that determines public policies, interacting with the intermediate dimensions as central aspects and with the individual dimensions of a sociodemographic, sociocultural and socioeconomic nature. These, in turn, feedback and once again influence the political will and Public policies, closing the systemic cycle. In addition, interactive control of the system is included. Conclusions : In addition to the models proposed in the national literature reviewed, abounding in its systemic approach contributes to facilitate the understanding of the monitoring of the Social determination in health in tuberculosis by the personnel in charge of providing sustainability of control towards elimination.

Tratamiento de COVID-19 en Panamá. La historia del inicio, estudio PanaCovid2020

Antecedentes En Panamá, durante los primeros cinco meses de pandemia, se reportaron 65,256 casos y 1,421 fallecimientos por COVID-19. Los tratamientos utilizados en pacientes hospitalizados durante este periodo fueron variando en la medida que surgía evidencia científica. Metodología Presentamos un estudio multicéntrico observacional, descriptivo, de corte transversal y retrospectivo de la terapéutica administrada en pacientes hospitalizados con COVID-19 en siete centros estatales de la República de Panamá, entre el 1 de marzo al 31 de julio de 2020. Se analizó el resultado de recuperado o fallecido en relación al uso de hidroxicloroquina, heparinas y esteroides. Resultados Se revisaron 837 expedientes. 60.7% pacientes eran hombres y la mediana de edad fue 53.6 años. Los tratamientos más utilizados fueron heparinas 84.7%, esteroides sistémicos 76.5%, azitromicina 65.5% e hidroxicloroquina en 41.1%. La frecuencia de uso de oxigenoterapia fue de cánula nasal 73,2%, máscara facial con reservorio 39%, cánula de alto flujo 8.9%, ventilación mecánica no invasiva 11.1% y ventilación invasiva en el 15.3%. Los esteroides mostraron mayor tasa de recuperación (OR 1.72 [1.16-2.54). Conclusiones El reto de abordar una nueva enfermedad, sin tratamiento conocido, con evolución y desenlace variable, llevó a la comunidad médica a utilizar medicamentos empíricos con potencial terapéutico incierto. Destacamos que desde muy temprano se administró esteroides sistémicos, heparinas y tocilizumab; actualmente con beneficios para pacientes con requerimientos de hospitalización. Además, se empleó técnicas de oxigenación, como la cánula de alto flujo y ventilación mecánica no invasiva, con dudosa efectividad; pero que hoy ya tienen un rol estudiado en la falla respiratoria por COVID-19. (provisto por Infomedic International)

Background: In Panama, during the first five months of the pandemic, 65,256 cases and 1,421 deaths due to COVID-19 were reported. The treatments used in hospitalized patients during this period varied as scientific evidence emerged. Methodology: We present a retrospective, descriptive, cross-sectional, observational, descriptive, multicenter study of the therapeutics administered in hospitalized patients with COVID-19 in seven state centers in the Republic of Panama, between March 1 and July 31, 2020. The outcome of recovered or deceased was analyzed in relation to the use of hydroxychloroquine, heparins and steroids. Results: A total of 837 files were reviewed. 60.7% of patients were men and the median age was 53.6 years. The most commonly used treatments were heparins 84.7%, systemic steroids 76.5%, azithromycin 65.5% and hydroxychloroquine in 41.1%. The frequency of oxygen therapy use was nasal cannula 73.2%, face mask with reservoir 39%, high-flow cannula 8.9%, noninvasive mechanical ventilation 11.1% and invasive ventilation in 15.3%. Steroids showed higher recovery rate (OR 1.72 [1.16-2.54). Conclusions: The challenge of dealing with a new disease, without known treatment, with variable evolution and outcome, led the medical community to use empirical drugs with uncertain therapeutic potential. We highlight the early administration of systemic steroids, heparins and tocilizumab; currently with benefits for patients requiring hospitalization. In addition, oxygenation techniques were used, such as high-flow cannula and noninvasive mechanical ventilation, with doubtful effectiveness, but which today have a studied role in respiratory failure due to COVID-19.   (provided by Infomedic International)

Androgen deprivation therapy mimicking acute coronary syndrome: A case report.

An 80-year-old man diagnosed with prostate cancer and under treatment with androgen deprivation therapy presented at the emergency room with chest pain, repolarization abnormalities and QT interval prolongation on electrocardiogram. An initial diagnosis of acute coronary syndrome was proposed, but biomarkers and coronary angiography were negative. Hydroelectrolyte balance and echocardiogram were also normal. Some weeks after drug withdrawal, repolarization changes reverted. A rare side effect of these drugs mimicking an acute coronary syndrome was the most probable diagnosis.

Malnutrición en una población de escolares en Santiago, República Dominicana / Malnutrition of an elementary school population in Santiago, Dominican Republic

Introducción: la malnutrición infantil representa uno de los problemas de salud pública más importantes de la República Dominicana (RD) y el mundo. A pesar de esto, actualmente, no existen estudios en la RD que describa el estado nutricional en los niños de la escuela primaria. Material y métodos: este estudio transversal describió las principales variables antropométricas en niños de 1ero a 6to de primaria en Santiago, RD, además de determinar la relación existente entre la antropometría y variables sociodemográficas. Resultados: de los 2,271 estudiantes estudiados, la media del peso fue 33,2 ± 11,4 kg, la talla fue 1,36 ± 0,13 m. La media del percentil fue 65,33 %. El 3.92 % (n=89) estuvo en bajo peso, el 17.57 % (n=399) estuvo en sobrepeso y el 22.94 % (n=521) estuvo en obesidad. Conclusión: el sobrepeso y la obesidad infantil fueron los trastornos más comunes en zonas rurales y urbanas, y tanto en centros privados como públicos

Introduction: Child malnutrition represents one of the most important public health issues in the Dominican Republic (DR) and the whole world. Despite this reality, there are currently no studies in the DR that describe the nutritional status in primary school children. Material and method: This cross-sectional study described the main anthropometric variables in children from elementary schools in Santiago, RD, in addition to determining the relationship between anthropometry status and some sociodemographic variables. Results: 2,271 participants were analyzed; the mean weight was 33.2 ± 11.4 kg, height was 1.36 ± 0.13 m. The mean percentile was 65.33%. 3.92% (n=89) were underweight, 17.57% (n=399) were overweight, and 22.94% (n=521) were obese. Conclusion: Childhood overweight and obesity was the most prevalent disorder, both in rural and urban areas, and both in private and public centers

A prevalence study in Guadalajara, Mexico, comparing tuberculin skin test and QuantiFERON-TB Gold In-Tube.

BACKGROUND: Tuberculosis (TB) is a prevalent disease throughout the world. The extent of TB illness in childhood is not clear; recent data shows that 10-20% of the cases are found in children under 15 years old. In 2017, 1 million children developed the disease, of which 9% were co-infected with HIV. METHODS: A cross-sectional study that analyzed 48 children diagnosed with HIV-infection in Guadalajara, Mexico. The tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT) were performed and compared to diagnose latent TB infection (LTBI). RESULTS: The average age was 9 years old (± 4), with an age range of 1-16 years; the 6-12-year-old group predominated with 50% of cases. 27 patients (56%) were male; 83% had received the BCG vaccination and 23% had a history of being contacts of TB cases. In the study, 40 patients (83%) were without immunosuppression; seven (15%) with moderate immunosuppression, and only one patient had severe immunodeficiency. Overall, 3 of the 48 children (6.2%) had a positive TST, while 8 out of 48 (16.6%) had a positive QFT. The concordance between the two tests was 89.6% (43/48) with Kappa = 0.5 (95% CI, 0.14-0.85). CONCLUSIONS: The QFT test represents an opportunity in the diagnosis of LTBI, particularly in pediatric HIV- patients. This is the first study that compares the two tests (TST and QFT) in children with HIV-infection in Guadalajara, Mexico.

Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite.

Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease, Borrelia burgdorferi (Bb), provides a model to study the evolution of host adaptation, as some Bb strains defined by their outer surface protein C (ospC) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with three Bb strains of different ospC genotypes. Bb burdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded to Bb survival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal of Bb, suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites.

Glucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches.

Botanical supplements derived from grapes are functional in animal model systems for the amelioration of neurological conditions, including cognitive impairment. Rats fed with grape extracts accumulate 3'-O-methyl-quercetin-3-O-ß-d-glucuronide (3) in their brains, suggesting 3 as a potential therapeutic agent. To develop methods for the synthesis of 3 and the related 4'-O-methyl-quercetin-7-O-ß-d-glucuronide (4), 3-O-methyl-quercetin-3'-O-ß-d-glucuronide (5), and 4'-O-methyl-quercetin-3'-O-ß-d-glucuronide (6), which are not found in the brain, we have evaluated both enzymatic semisynthesis and full chemical synthetic approaches. Biocatalysis by mammalian UDP-glucuronosyltransferases generated multiple glucuronidated products from 4'-O-methylquercetin, and is not cost-effective. Chemical synthetic methods, on the other hand, provided good results; 3, 5, and 6 were obtained in six steps at 12, 18, and 30% overall yield, respectively, while 4 was synthesized in five steps at 34% overall yield. A mechanistic study on the unexpected regioselectivity observed in the quercetin glucuronide synthetic steps is also presented.

An enquiry into antileishmanial activity and quantitative analysis of polyhydroxylated steroidal saponins from Solanum paniculatum L. leaves.

Solanum paniculatum L. is species whose fruits are widely consumed in Brazil as a tonic beverage with higher content of steroidal saponins. In this work, we developed an analytical method for the quantification of the eight saponins present in the 70 % ethanol extract from the leaves using ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS). Besides, the eight spirostanic saponins were screened for in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania (L.) amazonensis. Substances 1, 2 and 3 were found to be the most active compounds, with inhibitory concentration (IC50) values of 8.51 ± 4.38, 10.75 ± 6.85 and 10.45 ± 4.21 µM, respectively, against promastigote forms and effective concentration (EC50) values of >25, 17.73 ± 0.99 and 19.57 ± 0.84 µM, respectively, against amastigote forms. The cytotoxic test with compounds 1-3 evidenced low toxicity in murine macrophage cells, with values above 50 µM at concentration lower than 25 µM. These findings show that saponins 1-3 should be evaluated in further studies for the treatment of cutaneous leishmaniasis.

Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG.

Diffuse intrinsic pontine glioma (DIPG) is most commonly diagnosed based on imaging criteria, with biopsy often reserved for pontine tumors with imaging features not typical for DIPG (atypical DIPG, 'aDIPG'). The histopathologic and molecular spectra of the clinical entity aDIPG remain to be studied systematically. In this study, thirty-three patients with newly diagnosed pontine-centered tumors with imaging inconsistent with DIPG for whom a pathologic diagnosis was subsequently obtained were included. Neoplasms were characterized by routine histology, immunohistochemistry, interphase fluorescence in situ hybridization, Sanger and next-generation DNA/RNA sequencing, and genome-wide DNA methylome profiling. Clinicopathologic features and survival outcomes were analyzed and compared to those of a contemporary cohort with imaging features consistent with DIPG (typical DIPG, 'tDIPG'). Blinded retrospective neuroimaging review assessed the consistency of the initial imaging-based diagnosis and correlation with histopathology. WHO grade II-IV infiltrating gliomas were observed in 54.6% of the cases; the remaining were low-grade gliomas/glioneuronal tumors or CNS embryonal tumors. Histone H3 K27M mutation, identified in 36% of the cases, was the major prognostic determinant. H3 K27M-mutant aDIPG and H3 K27M-mutant tDIPG had similar methylome profiles but clustered separately from diffuse midline gliomas of the diencephalon and spinal cord. In the aDIPG cohort, clinicoradiographic features did not differ by H3 status, yet significant differences in clinical and imaging features were observed between aDIPG without H3 K27M mutation and tDIPG. Neuroimaging review revealed discordance between the classification of aDIPG and tDIPG and did not correlate with the histology of glial/glioneuronal tumors or tumor grade. One patient (3.1%) developed persistent neurologic deficits after surgery; there were no surgery-related deaths. Our study demonstrates that surgical sampling of aDIPG is well-tolerated and provides significant diagnostic, therapeutic, and prognostic implications, and that neuroimaging alone is insufficient to distinguish aDIPG from tDIPG. H3 K27M-mutant aDIPG is epigenetically and clinically similar to H3 K27M-mutant tDIPG.