Water-pipe smoking and serum testosterone levels in adult males in Qatar.

Water-pipe (WP) smoking is the most common method of tobacco consumption in the Middle-East and is rapidly spreading on a global scale. Although, water-pipe smoking is linked to various diseases, such as emphysema and various types of cancers, its effect on testosterone levels has yet to be investigated. This study explores the effect of water-pipe smoking on serum testosterone levels in males in Qatar. In this cross-sectional sample within a cohort study, we retrieved data for a total of 1000 male volunteers from the Qatar BioBank (QBB) project. A self-reported questionnaire was used to determine the water-pipe smoking status of participants. Moreover, participants were stratified based on the frequency of smoking. Total testosterone and sex hormone binding globulin (SHBG) were measured clinically, whereas free testosterone and bioavailable testosterone were calculated using Vermeulen's equation. Hormone values of 541 males (277 water-pipe smokers and 264 non-smokers) were compared using multiple regression analysis based on water-pipe smoking status after adjusting for confounding factors. No statistically significant difference was observed between WP smokers and non-water-pipe smokers in the likelihood of having lower or higher total testosterone, after adjustment for confounding factors. Similar results were found in free testosterone, bioavailable testosterone, and sex hormone binding globulin (all p>0.05). When compared with the reference group, both light and heavy water-pipe smokers had a similar likelihood of circulating low total testosterone levels (OR=0.83, 95% CI: 0.46-1.49; and OR=0.80, 95% CI: 0.43-1.49; respectively). Our results reveal, for the first time, that there is no significant change in total testosterone, free testosterone, bioavailable testosterone and sex hormone binding globulin in waterpipe smokers compared to non-water-pipe smokers. Therefore, we believe that further studies are needed to confirm the effect of water-pipe smoking on testosterone in different populations.This work was supported by the College of Medicine of Qatar University and grant QUST-2-CMED-2018-1 from Qatar University

Role of Interventional Radiology in Management of Gastrointestinal Bleeding

Gastrointestinal bleeding is a common and potentially life-threatening condition that requires prompt and effective management. Interventional radiology has emerged as a valuable tool in the management of gastrointestinal bleeding, offering minimally invasive techniques that can rapidly control bleeding and improve patient outcomes. This review aims to provide an overview of the role of interventional radiology in the management of gastrointestinal bleeding, including its various techniques and their efficacy. The review discusses the different interventional radiology procedures that can be used to diagnose and treat gastrointestinal bleeding. It also highlights the advantages of techniques used in evaluation and management, including their ability to localize and control bleeding, as well as their low complication rates and shorter recovery times compared to traditional surgical approaches. Furthermore, the review addresses the specific indications for interventional radiology in the management of gastrointestinal bleeding, as well as the role of interventional radiology in the setting of underlying conditions. Overall, this review provides a comprehensive overview of the role of interventional radiology in the management of gastrointestinal bleeding, highlighting its effectiveness and potential benefits for patients. It also emphasizes the need for further research and collaboration between interventional radiologists and gastroenterologists to optimize the use of these techniques in clinical practice

Reproducibility of the ribosomal RNA synthesis ratio in sputum and association with markers of mycobacterium tuberculosis burden

The MIND-IHOP study was funded by the IHOP grant (NIH R01 HL090335), Lung MicroCHIP grant (NIH U01 HL098964), and K24 grant (NIH K24 HL087713). These sources provided the funding to support participant enrollment and specimen collection. Emmanuel Musisi was supported by a scholarship from the Pulmonary Complications of AIDS Research Training Program (NIH D43 TW009607). N.D.W., R.M.S., J.L.D., and P.N. acknowledge funding from the U.S. National Institutes of Health (1R01AI127300-01A1). N.D.W. and M.I.V. acknowledge funding from the U.S. National Institutes of Health (1R21AI135652-01). N.D.W. acknowledges funding from Veterans Affairs (1IK2CX000914-01A1 and 1I01BX004527-01A1) and from the Doris Duke Charitable Foundation Clinical Scientist Development Award.There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. Importance This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.Publisher PDFPeer reviewe

Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

New approaches to the identification of biomarkers of infection and nerve damage in leprosy

2012 Spring.Includes bibliographical references.Leprosy is an ancient disease and the first disease discovered to be caused by a bacterium, Mycobacterium leprae. M. leprae is an obligate intracellular pathogen that targets the Schwann cells in the peripheral nerves. As a result of this infection nerve damage and deformity occur. There are three main obstacles that slow the progress in M. leprae research and diagnosis. The first obstacle is the absence of a good animal model to study host-pathogen interaction. The second is the absence of good biomarkers for leprosy diagnosis and sub grouping. The third obstacle is the inability to cultivate M. leprae in vitro, due to the extreme decay of the M. leprae genome and the resulting decline in the maintenance of metabolic pathways. This research thesis addresses each of these issues in turn. The first goal of this study was to improve using the only available animal model, the nine-banded armadillo (Dasypus novemcintus), by studying its molecular response to infection by M. leprae (host-pathogen interactions). Several molecular techniques were applied based on the new technology of "omics" and the availability of the partial genome sequence of the armadillo. Proteomic and lipidomic mass spectrometric profiles of infected and uninfected armadillo tissue (nerve, liver and spleen) were compared. The first partial armadillo nerve protein library was developed. The protein profile showed increased amounts of immunoglobulins IgG and IgM in the infected nerve. A decrease in a 15 kD protein that could be myelin P2 was observed in the infected nerve. We also detected antibodies against myelin P2 in the sera of leprosy patients. The lipid profile of armadillo tissues showed an increase in certain lipid groups, mainly neutral triacylglycerols (TAGs). These TAGs contained acyl chains of specific lengths and unsaturation (mono-and di-unsaturation) in all three types of infected tissues in comparison to naïve tissues. The lipidomics finding was supported by the detection of increased expression of several genes for unsaturated fatty acids and TAG synthesis such as stearoyl-CoA desaturase 9 (SCD9), elongase 5 (ELOVL5), diacylglycerol acyltransferase (DGAT) and fatty acid desaturase (∆5d) in the infected tissues. The second study focused on identifying needed biomarkers for the diagnosis of leprosy and differentiates between leprosy sub-groupings. In this case a mass spectrometric metabolomics approach was used to study the circulatory biomarkers in the sera of newly diagnosed untreated leprosy patients. We found a significant increase in the abundance of certain polyunsaturated fatty acids (PUFAs) and phospholipids in the high-bacterial index (BI) patients, when compared with the levels in the low-BI leprosy patients. These PUFAs are known to exert anti-inflammatory properties that may promote M. leprae survival. This finding is in agreement with the overall phenotype (increase anti-inflammation and high bacterial load) in the high-BI leprosy patients. The third part of this study addressed the inability to grow M. leprae in culture. Here the hypothesis was that a test of viability (using molecular genetics techniques), in the presence or absence of particular nutrients, would lead to identifying a medium or nutrients required for the in vitro maintenance of M. leprae. Based on the M. leprae genome and the genome-based metabolic databases (Metagrowth), several genes were found to be lost from major metabolic pathways in M. leprae. Therefore, the objective was to provide in the medium those metabolites missing because of the pathway disruption. Different culture media were tested to maintain M. leprae in vitro. The viability of the bacteria in different media formulations was compared based on testing expression of several M. leprae transcripts and the 16S rRNA using quantitative real-time PCR (qRT-PCR). Surprisingly, the results from all of these media trials demonstrated that the simple addition of 2% glycerol to 7H12 media supported M. leprae viability up to 21 days, compared to the basal medium (7H12) that showed a decrease in M. leprae viability after 7 days. On the other hand, the addition of 0.1% sodium thioglycolate to 7H12 media reduced M. leprae viability by 3 and 7 days. Many leprosy patients suffer irreversible peripheral nerve damage resulting in blindness or other disabilities as a consequence of M. leprae infection. Until now the mechanisms of nerve damage have not been fully elucidated due to lack of in vitro condition to cultivate M. leprae and animal model to study host-pathogen interaction. In this research dissertation progress was made to understand M. leprae-pathogen interaction. Using new approaches (metabolomics, proteomics and lipidomics) helped in finding marker (s) for the infection and nerve damage in leprosy

Comparison of pro- and anti-inflammatory responses in paired human primary airway epithelial cells and alveolar macrophages

Abstract Background Airway epithelial cells and alveolar macrophages (AMs) are the first line of defense in the lung during infection. Toll-like receptor (TLR) agonists have been extensively used to define the regulation of inflammation in these cells. However, previous studies were performed in non-paired airway epithelial cells and AMs. The major goal of our study was to compare the pro- and anti-inflammatory responses of paired human primary airway epithelial cells and AMs to TLR3 and TLR4 agonists. Methods Tracheobronchial epithelial cells (TBEC) and AMs from four smokers and four non-smokers without lung disease were cultured with or without Poly(I:C) (PIC) (a TLR3 agonist) or LPS (a TLR4 agonist) for 4, 24 and 48 h. The immune responses of paired cells were compared. Results TBEC and AMs showed stronger pro-inflammatory cytokine (e.g., IL-8) responses to PIC and LPS, respectively. TLR3 and TLR4 mRNA levels were similar in non-stimulated TBEC and AMs. However, PIC stimulation in AMs led to sustained up-regulation of the immune negative regulators Tollip and A20, which may render AMs less sensitive to PIC stimulation than TBEC. Unlike AMs, TBEC did not increase NF-κB activation after LPS stimulation. Interestingly, smoking status was correlated with less TLR3 and IRAK-M expression in non-stimulated TBEC, but not in AMs. PIC-stimulated TBEC and LPS-stimulated AMs from smokers vs. non-smokers produced more IL-8. Finally, we show that expression of A20 and IRAK-M is strongly correlated in the two paired cell types. Conclusions By using paired airway epithelial cells and AMs, this study reveals how these two critical types of lung cells respond to viral and bacterial pathogen associated molecular patterns, and provides rationale for modulating immune negative regulators to prevent excessive lung inflammation during respiratory infection

Impact of water-pipe smoking on testosterone levels in Qatari males

Introduction Water-pipe (WP) smoking is the most widespread tobacco use in the Middle-East, and is rapidly spreading globally. Meanwhile, changes in testosterone levels have been linked to various diseases including type 2 diabetes and erectile dysfunction. This investigation addresses an important gap in the outcome of WP smoking on testosterone levels. Aim To explore the outcome of WP smoke on serum levels of total testosterone (TT), free testosterone (FT), bioavailable testosterone (bioT) and sex hormone-binding globulin (SHBG) among men in Qatar. Methods This is a cross-sectional cohort study based on data gathered from a total of 1000 volunteer men from Qatar BioBank (QBB). To determine the WP and Cigarette smoking status, a self-reported questionnaire was used. TT and SHBG were measured clinically, whereas FT and BioT were calculated using Vermeulen’s equation. Hormone values were compared using multiple regression analysis based on WP smoking status after adjusting for appropriate confounding factors. Results Once exclusion criteria were applied, 541 males (277 WP smokers and 264 non-smokers) were included in the analysis. After adjustment for cofounding factors, no statistical significant difference was observed in TT, FT, SHBG, and BioT between WP smokers and non-smokers (all p > 0.05). Furthermore, Similar results were found in non-adjusted regression model, while only age was shown to significantly affect androgens level (P= 0.014). Conclusions In this study we report, for the first time, that there was no significant change in TT, FT, BioT and SHBG in WP smokers when compared to non-WP smokers. Funding This study was supported by a Qatar University Student Grant