Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents.

The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb.

Quality of life and surgical outcomes of robotic retromuscular ventral hernia repair using a new hybrid mesh reinforcement.

Purpose: The purpose of this study is to prospectively evaluate surgical and quality of life (QoL) outcomes of robotic retromuscular ventral hernia repair (rRMVHR) using a new hybrid mesh in high-risk patients.

Methods: Data was prospectively collected for patients classified as high-risk based on the modified ventral hernia working group (VHWG) grading system, who underwent rRMVHR using Synecor™ Pre hybrid mesh in a single center, between 2019 and 2020. Pre-, intra- and postoperative variables including hernia recurrence, surgical site events (SSE), hernia-specific quality of life (QoL), and financial costs were analyzed.

Identification of β-Lactams Active against by a Consortium of Pharmaceutical Companies and Academic Institutions.

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill (Mtb).

Cyclohexyl-griselimycin Is Active against Mycobacterium abscessus in Mice.

Cyclohexyl-griselimycin is a preclinical candidate for use against tuberculosis (TB). Here, we show that this oral cyclodepsipeptide is also active against the intrinsically drug-resistant nontuberculous mycobacterium Mycobacterium abscessus and in a mouse model of infection. This adds a novel advanced lead compound to the M.

Grazing diverse combinations of tanniferous and nontanniferous legumes: implications for foraging behavior, performance, and hair cortisol in beef cattle.

A diversity of forages with different types and concentrations of nutrients and plant secondary compounds may lead to complementary relationships that enhance cattle performance and welfare. We determined whether grazing combinations of tanniferous legumes (Lotus corniculatus, birdsfoot trefoil [BFT], Onobrychis viciifolia, sainfoin [SF]), and alfalfa [ALF] (Medicago sativa) influence foraging behavior, performance, and hair cortisol concentration in beef cattle compared with grazing the same legumes as monocultures. Twenty-one pairs of heifers grazed three spatial replications of seven treatments: monocultures of BFT, SF, or ALF, and all possible two- and three-way choices among strips of these legumes: SF-BFT, ALF-BFT, ALF-SF, and ALF-SF-BFT in two periods of 25 d each (adaptation phase + experimental period) during two consecutive years.

Integrative Analysis of Human Macrophage Inflammatory Response Related to Virulence.

(Mtb), the etiological agent of tuberculosis, kills 1.5 to 1.7 million people every year.

Maximal Oxygen Consumption Requirements in Professional North American Ice Hockey.

Ferland, P-M, Marcotte-L'Heureux, V, Roy, P, Carey, V, Charron, J, Lagrange, S, Leone, M, and Comtois, AS. Maximal oxygen consumption requirements in professional North American ice hockey. J Strength Cond Res 35(4): 1586-1592, 2021-This study was designed to measure preseason on-ice relative V̇o2max of professional ice-hockey players (n = 101 National Hockey League [NHL], 42 American Hockey League [AHL], 4 East Coast Hockey League [ECHL], and 15 Canadian Hockey League [CHL]) throughout 17 years and compare it between generations, league level, and position, and to verify if it was related to season and NHL career statistics.

Grazing diverse combinations of tanniferous and non-tanniferous legumes: Implications for beef cattle performance and environmental impact.

We tested the effect of increasingly diverse combinations of tanniferous legumes (birdsfoot trefoil-BFT, sainfoin-SF) and alfalfa (ALF) on cattle performance, methane (CH) emissions and nitrogen (N) balance. Pairs of heifers (401 ± 49.6 kg) grazed three spatial replications of 7 treatments (n = 3/treatment): monocultures (BFT, SF, ALF) and all possible 2- and 3-way choices among strips of these legumes in a completely randomized block design of two 15-d periods during 2 consecutive years.

Unmet healthcare needs among migrants without medical insurance in Montreal, Canada.

While access to healthcare for permanent residents in Canada is well known, this is not the case for migrants without healthcare coverage. This is the first large-scale study that examines the unmet healthcare needs of migrants without healthcare coverage in Montreal. 806 participants were recruited: 436 in the community and 370 at the NGO clinic.

Contrast Training Generates Post-Activation Potentiation and Improves Repeated Sprint Ability in Elite Ice Hockey Players.

The purpose of this study was to measure the generating effects of Contrast Training (CT) on 6-hour post-activation potentiation (PAP) and its influence on jumping and on on-ice repeated sprint performance in ice hockey players. Forty-one participants were divided in two groups: experimental (EG) and control group (CG). The EG followed the CT PAP protocol which consisted of 5 sets of 5 half inertia back squat superset with 6 squat jumps.

Tannin-containing legumes and forage diversity influence foraging behavior, diet digestibility, and nitrogen excretion by lambs1,2.

Diverse combinations of forages with different nutrient profiles and plant secondary compounds may improve intake and nutrient utilization by ruminants. We tested the influence of diverse dietary combinations of tannin- (sainfoin-Onobrichis viciifolia; birdsfoot trefoil-Lotus corniculatus) and non-tannin- (alfalfa-Medicago sativa L.) containing legumes on intake and diet digestibility in lambs.

Bactericidal Disruption of Magnesium Metallostasis in Mycobacterium tuberculosis Is Counteracted by Mutations in the Metal Ion Transporter CorA.

A defining characteristic of treating tuberculosis is the need for prolonged administration of multiple drugs. This may be due in part to subpopulations of slowly replicating or nonreplicating bacilli exhibiting phenotypic tolerance to most antibiotics in the standard treatment regimen. Confounding this problem is the increasing incidence of heritable multidrug-resistant A search for new antimycobacterial chemical scaffolds that can kill phenotypically drug-tolerant mycobacteria uncovered tricyclic 4-hydroxyquinolines and a barbituric acid derivative with mycobactericidal activity against both replicating and nonreplicating Both families of compounds depleted of intrabacterial magnesium.

Dual-Pharmacophore Pyrithione-Containing Cephalosporins Kill Both Replicating and Nonreplicating .

The historical view of β-lactams as ineffective antimycobacterials has given way to growing interest in the activity of this class against () in the presence of a β-lactamase inhibitor. However, most antimycobacterial β-lactams kill only or best when the bacilli are replicating. Here, a screen of 1904 β-lactams led to the identification of cephalosporins substituted with a pyrithione moiety at C3' that are active against under both replicating and nonreplicating conditions, neither activity requiring a β-lactamase inhibitor.

Opposing reactions in coenzyme A metabolism sensitize to enzyme inhibition.

(Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb's cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4'-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT.

Laser hair removal after surgery vs. surgery alone for the treatment of pilonidal cysts: a retrospective case-control study.

Background: Based on the presumed role of hair in pilonidal cyst (PNC) pathogenesis, laser epilation has been used to decrease recurrences. However, most of the data rely on case reports and uncontrolled series, and the rare controlled studies reported conflicting results. The objective of this study was to investigate the efficacy of laser hair removal (LHR) to decrease the recurrence rate after surgery of PNC vs.

-Acetylglucosamine-1-Phosphate Transferase, WecA, as a Validated Drug Target in Mycobacterium tuberculosis.

The mycobacterial phosphoglycosyltransferase WecA, which initiates arabinogalactan biosynthesis in , has been proposed as a target of the caprazamycin derivative CPZEN-45, a preclinical drug candidate for the treatment of tuberculosis. In this report, we describe the functional characterization of mycobacterial WecA and confirm the essentiality of its encoding gene in by demonstrating that the transcriptional silencing of is bactericidal and in macrophages. Silencing also conferred hypersensitivity of to the drug tunicamycin, confirming its target selectivity for WecA in whole cells.

Comparison of two picosecond lasers to a nanosecond laser for treating tattoos: a prospective randomized study on 49 patients.

Background: Q-switched nanosecond lasers demonstrated their efficacy in treating most types of tattoos, but complete disappearance is not always achieved even after performing numerous laser sessions. Picosecond lasers are supposed to be more efficient in clearing tattoos than nanosecond lasers, but prospective comparative data remain limited.

Objective: To compare on different types of tattoos the efficacy of a nanosecond laser with two types of picosecond lasers.

Pain and quality of life evaluation in patients with localized epidermolysis bullosa simplex.

Background: A localized form of epidermolysis bullosa simplex (EBS-l) is considered one of the mildest forms of epidermolysis bullosa (EB), with blisters limited to the palms and soles. However, these lesions can be very painful. The aim of the study was to characterize pain in patients with EBS-l and evaluate its impact on quality of life (QoL).

Feeding value of whole raw soya beans as a protein supplement for beef cattle consuming low-quality forages.

Experiments (Exp) I and II were conducted to compare raw whole soya beans (WSB), roasted (rWSB) or other protein sources as supplements of low-quality forages fed ad libitum to beef cattle, upon DM intake (DMI), ruminal and blood parameters, and animal performance. Exp I: treatments for wheat straw fed to four ruminally cannulated steers were (i) Control-WS: no supplement; (ii) WSB-WS: whole soya beans; (iii) rWSB-WS: roasted WSB; and (iv) SBM-WS: soybean meal-wheat midds mixture; all fed at 1.4 kg DM/day.