The Xpert® MTB/RIF cycle threshold value predicts M. tuberculosis transmission to close contacts in a Brazilian prospective multicenter cohort.

Background: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated.

Determinants of losses in the tuberculosis infection cascade of care among children and adolescent contacts of pulmonary tuberculosis cases: A Brazilian multi-centre longitudinal study.

Background: Approximately 10% of the global tuberculosis (TB) burden is in children. Identification, diagnosis, and early treatment of infection (TBI) is critical to prevent progression to TB in children. The risk of TB, including severe disease, is highest in children <5 years old.

Possible sex difference in latent tuberculosis infection risk among close tuberculosis contacts.

Objectives: More men than women develop and die of tuberculosis (TB). Fewer data exist on sex differences in latent TB infection (LTBI). We assessed for potential sex differences in LTBI acquisition among close TB contacts.

Prevalence and Clinical Profiling of Dysglycemia and HIV Infection in Persons With Pulmonary Tuberculosis in Brazil.

Background: There are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries.

Methods: We assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM.

Lessons Learned from Implementation of an Interferon Gamma Release Assay to Screen for Latent Tuberculosis Infection in a Large Multicenter Observational Cohort Study in Brazil.

The interferon gamma release assay (IGRA) has emerged as a useful tool for identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms such as the QuantiFERON-TB Gold Plus (QFT-Plus) assay. This test has been incorporated into several guidelines worldwide and has recently been considered by the World Health Organization (WHO) for the diagnosis of LTBI.

The Effect of Diabetes and Prediabetes on Antituberculosis Treatment Outcomes: A Multicenter Prospective Cohort Study.

Background: It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB).

Methods: Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion.

Determinants of losses in the latent tuberculosis infection cascade of care in Brazil.

Introduction: Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil.

Methods: Close contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6-24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected.

Tuberculosis Burden and Determinants of Treatment Outcomes According to Age in Brazil: A Nationwide Study of 896,314 Cases Reported Between 2010 and 2019.

Approximately 1.4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide public health policy implementation and clinical management to improve outcomes.

Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study.

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.

Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years.

The Effect of Diabetes and Prediabetes on Mycobacterium tuberculosis Transmission to Close Contacts.

Background: It is unknown whether dysglycemia is associated with Mycobacterium tuberculosis transmission.

Methods: We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary tuberculosis and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment.

Novel stepwise approach to assess representativeness of a large multicenter observational cohort of tuberculosis patients: The example of RePORT Brazil.

Background: A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important.

Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period.

Malnourishment during early lactation disrupts the ontogenetic distribution of the CART and α-MSH anorexigenic molecules in the arcuate/paraventricular pathway and lateral hypothalamus in male rats.

Developmental malnourishment impacts the energetic metabolism control throughout life. In rat offspring, a 0% protein diet during the first 10 days of lactation results in leptin resistance and in alterations in: feeding behavior, serum leptin and neuropeptide Y (NPY) levels in the hypothalamic arcuate nucleus (ARC)/paraventricular (PVN) pathway. Here, the distributions of alpha-melanocyte stimulating hormone (α-MSH) and cocaine and amphetamine regulated transcript (CART), anorexigenic molecules, were immunohistochemically assessed in the ARC, PVN and lateral hypothalamus (LH) nuclei.

Determinants of losses in the latent tuberculosis cascade of care in Brazil: A retrospective cohort study.

Background: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil.

Methods: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records.

Maternal protein-free diet during lactation programs male Wistar rat offspring for increased novelty-seeking, locomotor activity, and visuospatial performance.

It is well established that chronic undernutrition has detrimental impacts on brain development and maturation. However, protein malnutrition during the period specifically encompassing the brain growth spurt has not been widely studied, particularly regarding its effects on adolescent and adult offspring behavior. Here, we assessed the effects of a protein-free diet during the 1st 10 postnatal days on the macronutrient content of the milk produced by lactating Wistar rats, on their maternal behavior, and on the offspring's behavior.

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.

Background: Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria.

Revisiting the Heterogeneous IFN-γ Response of Bacille of Calmette-Guérin (BCG)-Revaccinated Healthy Volunteers in a Randomized Controlled Trial: Effect of the Body Mass Index and of the IFNG+874 A/T Polymorphism.

In trials evaluating the immune responses to Bacille of Calmette-Guérin (BCG), the genetic background and the nutritional status are host-related factors that could affect the heterogeneity in these parameters. The IFNG+874 A/T (rs 62559044) polymorphism has been reported to influence the IFN-γ production by BCG-vaccinated individuals challenged in vitro with mycobacterial antigens. The body mass index (BMI) is a proxy for the nutritional status and has been associated both with the susceptibility to tuberculosis and with the IFN-γ response.

Evolution and future of skull base surgery: the paradigm of skull base meningiomas.

Background: Skull base meningiomas represent the paradigm for the evolution of skull base surgery within the past 50 years into a distinct neurosurgical subspecialty.

Methods: From 2005 to 2011, 117 patients with cranial base meningiomas underwent surgical resection. Extent of resection, histologic grade, complications, functional status, and recurrence-free and overall survival data are presented.

Maternal malnutrition during lactation alters gonadotropin-releasing hormone expression in the hypothalamus of weaned male rat pups.

Gonadotropin-releasing hormone (GnRH) is the key hormone regulating reproduction. Its feedback regulation is exercised by estradiol. The early postnatal period is critical for sexual differentiation.

Influence of donor cocaine use on outcome after cardiac transplantation: analysis of the United Network for Organ Sharing Thoracic Registry.

Heart transplantation from donors with a history of cocaine abuse remains controversial. Therefore, we examined the consequence of donor cocaine-use history on all-cause mortality and the development of coronary artery disease after heart transplantation. Using the United Network for Organ Sharing Thoracic Registry we identified 9,217 first-time heart-only adult transplant recipients between January 1999 and December 2003, and then divided this cohort into sub-groups based on the reported history of donor cocaine use.

Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis.

Aging is characterized by compromised organ and tissue function. A decrease in stem cell number and/or activity could lead to the aging-related decline in tissue homeostasis. We have analyzed how the process of aging affects germ line stem cell (GSC) behavior in the Drosophila testis and report that significant changes within the stem cell microenvironment, or niche, occur that contribute to a decline in stem cell number over time.

Discovery of tMAC: a Drosophila testis-specific meiotic arrest complex paralogous to Myb-Muv B.

The Drosophila Myb-Muv B (MMB)/dREAM complex regulates gene expression and DNA replication site-specifically, but its activities in vivo have not been thoroughly explored. In ovarian amplification-stage follicle cell nuclei, the largest subunit, Mip130, is a negative regulator of replication, whereas another subunit, Myb, is a positive regulator. Here, we identified a mutation in mip40 and generated a mutation in mip120, two additional MMB subunits.