Protocol for studying cough frequency in people with pulmonary tuberculosis.

INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission

DNA damage and repair in endometrial cancer in correlation with the hOGG1 and RAD51 genes polymorphism

The cellular reaction to the DNA-damaging agents may modulate individual’s cancer susceptibility. This reaction is mainly determined by the efficacy of DNA repair, which in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphism. The hOGG1 gene encodes a glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both proteins can be involved in the repair of DNA lesions, which are known to contribute to endometrial cancer. In the present work we determined the extent of basal DNA damage and the efficacy of removal of DNA damage induced by hydrogen peroxide and N-methyl-N′-nitro N-nitrosoguanidyne (MNNG) in peripheral blood lymphocytes of 30 endometrial cancer patients and 30 individuals without cancer. The results from DNA damage and repair study were correlated with the genotypes of two common polymorphisms of the hOGG1 and RAD51 genes: a G>C transversion at 1245 position of the hOGG1 gene producing a Ser → Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G>C substitution at 135 position of the RAD51 gene (the 135G>C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis and genotypes were determined by restriction fragment length polymorphism PCR. We observed a strong association between endometrial cancer and the C/C genotype of the 135G>C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and endometrial cancer occurrence in subjects with a high level of basal DNA damage. We did not observe any correlation between the Ser326Cys polymorphism of the hOGG1 gene and endometrial cancer. Our result suggest that the 135G>C polymorphism of the RAD51 gene may be linked to endometrial cancer and can be considered as an additional marker of this disease

The Achievement of a Decentralized Water Management Through Stakeholder Participation: An Example from the Drôme River Catchment Area in France (1981–2008)

International audienceDifferent water Acts (e.g., the European Water Framework Directive) and stakeholders involved in aquatic affairs have promoted integrated river basin management (IRBM) over recent decades. However, few studies have provided feedback on these policies. The aim of the current article is to fill this gap by exploring how local newspapers reflect the implementation of a broad public participation within a catchment of France known for its innovation with regard to this domain. The media coverage of a water management strategy in the Drôme watershed from 1981 to 2008 was investigated using a content analysis and a geographic information system (GIS). We sought to determine what public participation and decentralized decision-making can be in practice. The results showed that this policy was integrated because of its social perspective, the high number of involved stakeholders, the willingness to handle water issues, and the local scale suitable for participation. We emphasized the prominence of the watershed scale guaranteed by the local water authority. This area was also characterized by compromise, arrangements, and power dynamics on a fine scale. We examined the most politically engaged writings regarding water management, which topics each group emphasized, and how the groups agreed and disagreed on issues based on their values and context. The temporal pattern of participation implementation was progressive but worked by fits and starts

JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells

Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas. Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin. Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as β-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen. We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen. Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5′-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells. In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation. Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation. Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation. These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic phenotype and may enhance our understanding of the role of viral proteins in glycolytic tumor metabolism, thus providing useful targets for the treatment of virus-induced tumors

Early Hypothalamic FTO Overexpression in Response to Maternal Obesity – Potential Contribution to Postweaning Hyperphagia

Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood