Mycobacteriophage D29 Lysin B exhibits promising anti-mycobacterial activity against drug-resistant Mycobacterium tuberculosis.

IMPORTANCE: To combat the rapidly emerging drug-resistant M. tuberculosis, it is now essential to look for alternative therapeutics. Mycobacteriophages can be considered as efficient therapeutics due to their natural ability to infect and kill mycobacteria including M. tuberculosis. Here, we have exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This study is novel in terms of targeting a multi-drug-resistant pathogenic strain of M. tuberculosis with LysB and also examining the combination of anti-TB drugs and LysB. All the experiments include external administration of LysB. Therefore, the remarkable lytic activity of LysB overcomes the difficulty to enter the complex cell envelope of mycobacteria. Targeting the intracellularly located M. tuberculosis by LysB and non-toxicity to macrophages take the process of the development of LysB as a drug one step ahead, and also, the interaction studies with rifampicin and isoniazid will help to form a new treatment regimen against tuberculosis.

Demographic Profile and Service-Connection Trends of Posttraumatic Stress Disorder and Traumatic Brain Injury in US Veterans Pre- and Post-9/11.

INTRODUCTION: This study seeks to understand the demographic changes in the active-duty service member profile, both prior to and following September 11, 2001 (9/11). The study analyzed diagnosis of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and measures of severity of those diagnoses as recorded in service-connection ratings (percent disability). METHODS: A retrospective cohort-study of military veterans who received care at Veterans Health Administration medical centers between December 1998 and May 2014 was conducted based on clinical data recorded and stored within the Corporate Data Warehouse. RESULTS: A cohort of 1,339,937 veterans received an inpatient or outpatient diagnosis of PTSD and/or TBI. The cohort was divided into 4 service period groups and 3 diagnosis categories. The service periods included pre-9/11 (n = 1,030,806; 77%), post-9/11 (n = 204,083; 15%), overlap-9/11 (n = 89,953; 7%), and reentered post-9/11 (n = 15,095; 1%). The diagnosis categories included PTSD alone (n = 1,132,356; 85%), TBI alone (n = 100,789; 7%) and PTSD+TBI (n = 106,792; 8%). Results of the post-9/11 group revealed significant changes, including (1) increase of veterans with PTSD+TBI; (2) increase of female veterans with PTSD+TBI; and (3) increase of severity level of diagnosed PTSD/TBI as evidenced by higher service-connected disability pensions at younger age in the post-9/11 group. Additionally, data revealed unequal distribution of veterans with PTSD+TBI across geographic areas. CONCLUSIONS: The veteran of the post-9/11 service period does not mirror the veteran of the pre-9/11 service period. Findings are valuable for policy making, allocation of resources, and for reconsidering the prevailing paradigm for treating veterans with PTSD and/or TBI.

The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study.

BACKGROUND: Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported. METHODS AND PARTICIPANTS: We evaluated effects of single 10 mg doses of lorcaserin on the subjective and reinforcing effects of cocaine, using a randomized, double-blind, within-subject, cross-over design. Male, non-treatment-seeking, regular cocaine users received either single doses of oral placebo (n = 9) or lorcaserin (n = 9), followed by low- or high- doses of intravenous cocaine (0.23 or 0.46 mg/kg-injection). They were then allowed to self-administer the lower dose of cocaine. RESULTS: Cocaine was well tolerated after lorcaserin pretreatment. Oral lorcaserin did not modify the number of cocaine injections self-administered. However, it prolonged the time over which participants made intravenous choices relative to the duration of monetary (cash) decisions. Lorcaserin increased ratings of 'high' and 'stimulated' after low-dose cocaine or vehicle, but decreased craving for cocaine after intravenous vehicle. It also caused small but significant increases in heart rate following noncontingent injections of intravenous placebo or cocaine. When active cocaine was self-administered, lorcaserin decreased heart rate after selection of a monetary choice, but increased it following an intravenous choice. CONCLUSIONS: Combined treatment with cocaine and lorcaserin was safe in a limited number of subjects, but did not diminish cocaine-motivated behavior or drug-induced 'high'. Some positive subjective effects of cocaine were enhanced by lorcaserin, and it delayed intravenous choices and decreased craving under some conditions. Effects on heart rate depended on the type of reinforcer being self-administered. TRIAL REGISTRATION: clinicaltrials.gov Identifier, NCT02680288.