OXA β-lactamases from spp. are membrane bound and secreted into outer membrane vesicles.

β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs.

OXA β-lactamases from spp. are membrane-bound and secreted into outer membrane vesicles.

β-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced β-lactamases was performed that revealed a predominance of putative lipidated enzymes in the class D OXAs.

Reduction of hyperglycemia in STZ-induced diabetic mice by prophylactic treatment with heat-killed : possible effects on glucose utilization, mitochondrial uncoupling, and oxidative stress in liver and skeletal muscle.

Background: In addition to conventional treatment and modifications in physical activity and diet, alternative strategies have been investigated to manage, prevent, or delay diabetes in humans. In this regard, one strategy has relied on the immunomodulatory properties of mycobacteria, whereby Bacillus Calmette-Guerin, an attenuated live strain of , has been shown to improve glycemic control in patients with diabetes and to alleviate hyperglycemia in selected murine models of diabetes. A novel heat-killed (HK) whole-cell preparation of () is currently under development as a potential food supplement; nevertheless, its potential bioactivity remains largely unknown.

The effect of fresh and used ankle taping on lower limb biomechanics in sports specific movements.

Objectives: We aimed to investigate the effects of ankle taping on lower extremity biomechanics related to injury development and how these effects change after sports-specific use.

Design: Randomized, repeated measures design with three conditions: Barefoot, tape applied fresh, and tape after sports-specific use (between-subject factor: sex).

Methods: Twenty-five healthy participants (ten female) performed sports-specific movements, including running, drop jumping, and 180° change of direction, under the three conditions.

In-cell kinetic stability is an essential trait in metallo-β-lactamase evolution.

Protein stability is an essential property for biological function. In contrast to the vast knowledge on protein stability in vitro, little is known about the factors governing in-cell stability. Here we show that the metallo-β-lactamase (MBL) New Delhi MBL-1 (NDM-1) is a kinetically unstable protein on metal restriction that has evolved by acquiring different biochemical traits that optimize its in-cell stability.

Metallo-β-lactamases and a tug-of-war for the available zinc at the host-pathogen interface.

Metallo-β-lactamases (MBLs) are zinc-dependent hydrolases that inactivate virtually all β-lactam antibiotics. The expression of MBLs by Gram-negative bacteria severely limits the therapeutic options to treat infections. MBLs bind the essential metal ions in the bacterial periplasm, and their activity is challenged upon the zinc starvation conditions elicited by the native immune response.

Key components and contrasts in the nitrogen budget across a US-Canadian transboundary watershed.

Watershed nitrogen (N) budgets provide insights into drivers and solutions for groundwater and surface water N contamination. We constructed a comprehensive N budget for the transboundary Nooksack River Watershed (British Columbia, Canada and Washington, US) using locally-derived data, national statistics and standard parameters. Feed imports for dairy (mainly in the US) and poultry (mainly in Canada) accounted for 30 and 29% of the total N input to the watershed, respectively.

Specific Protein-Membrane Interactions Promote Packaging of Metallo-β-Lactamases into Outer Membrane Vesicles.

Outer membrane vesicles (OMVs) act as carriers of bacterial products such as plasmids and resistance determinants, including metallo-β-lactamases. The lipidated, membrane-anchored metallo-β-lactamase NDM-1 can be detected in Gram-negative OMVs. The soluble domain of NDM-1 also forms electrostatic interactions with the membrane.

Cytokine/Chemokine Release Patterns and Transcriptomic Profiles of LPS/IFNγ-Activated Human Macrophages Differentiated with Heat-Killed , M-CSF, or GM-CSF.

Macrophages (Mφs) are instrumental regulators of the immune response whereby they acquire diverse functional phenotypes following their exposure to microenvironmental cues that govern their differentiation from monocytes and their activation. The complexity and diversity of the mycobacterial cell wall have empowered mycobacteria with potent immunomodulatory capacities. A heat-killed (HK) whole-cell preparation of () has shown promise as an adjunctive immunotherapeutic agent for the treatment of cancer.

Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.

Antimicrobial resistance is one of the major problems in current practical medicine. The spread of genes coding for resistance determinants among bacteria challenges the use of approved antibiotics, narrowing the options for treatment. Resistance to carbapenems, last resort antibiotics, is a major concern.

Impact of the "Mind the risk" Campaign of Sociedade Brasileira de Ortopedia e Traumatologia on Risk Perception and Use of the Surgical Checklist by Brazilian Orthopedists.

 To analyze the impact of the educational actions included in the "Mind the Risk" campaign of Sociedade Brasileira de Traumatologia e Ortopedia (Brazilian Society of Traumatology and Orthopedics, SBOT, in Portuguese), to increase the perception of the risk involved in the surgical activity and the use of the surgical checklist.  A comparative research was performed during the 50th Brazilian Congress on Orthopedics and Traumatology (50° CBOT, in Portuguese) in November 2018, using a questionnaire similar to the one used in previous two versions.  The number of participants was 730, corresponding to 18,7% of the total of 3,903 enrolled in the 50° CBOT.

Impact of the Strategies Adopted to Face the COVID-19 Pandemic in a Brazilian Reference Institute for High Complexity Surgery in Orthopedics and Traumatology.

COVID-19 pandemics required substantial reorganization and adaptation of healthcare services all over the world. This study aims to analyze the effect of operational strategies implemented in Brazil to manage the extra strain placed on healthcare services by the COVID-19 pandemic of 2020. In particular, this investigation examines the strategy to convert an institute specialized in elective orthopedic procedures of high complexity into a trauma unit for all musculoskeletal trauma patients of an entire federative unit.

Molecular Bases of the Membrane Association Mechanism Potentiating Antibiotic Resistance by New Delhi Metallo-β-lactamase 1.

Resistance to last-resort carbapenem antibiotics is an increasing threat to human health, as it critically limits therapeutic options. Metallo-β-lactamases (MBLs) are the largest family of carbapenemases, enzymes that inactivate these drugs. Among MBLs, New Delhi metallo-β-lactamase 1 (NDM-1) has experienced the fastest and largest worldwide dissemination.

Mitochondrial bioenergetics, uncoupling protein-2 activity, and reactive oxygen species production in the small intestine of a TNBS-induced colitis rat model.

Inflammatory bowel disease (IBD) is often associated with a decrease in energy-dependent nutrient uptake across the jejunum that serves as the main site for absorption in the small intestine. This association has prompted us to investigate the bioenergetics underlying the alterations in jejunal absorption in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in rats. We have found that mitochondrial oxygen consumption did not change in state 2 and state 3 respirations but showed an increase in state 4 respiration indicating a decrease in the respiratory control ratio of jejunal mitochondria during the peak of inflammation.

Absence of effect of the antiretrovirals Duovir and Viraday on mitochondrial bioenergetics.

Most toxicity associated with antiretroviral drugs is thought to result from disruption of mitochondrial function. Unfortunately, there are no validated laboratory markers for clinically assessing the onset of mitochondrial toxicity associated with antiretroviral therapy. In a previous study on mitochondrial hepatocytes, the protease inhibitor lopimune was shown to induce mitochondrial toxicity by increasing reactive oxygen species (ROS) production and decreasing respiratory control ratio (RCR) reflecting compromised mitochondrial efficiency in adenosine triphosphate production.

Defining Genome-Wide Expression and Phenotypic Contextual Cues in Macrophages Generated by Granulocyte/Macrophage Colony-Stimulating Factor, Macrophage Colony-Stimulating Factor, and Heat-Killed Mycobacteria.

Heat-killed (HK) (NCTC13365) is currently being evaluated in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the molecular underpinnings underlying immunomodulatory properties of HK are still largely undefined. To fill this void, we sought to perform immunophenotyping, chemokine/cytokine release analysis and genome-wide characterization of monocyte-derived macrophages (MDM) in which monocytes were originally isolated from healthy donors and differentiated by HK (Mob-MDM) relative to macrophage colony-stimulating factor (M-MDM) and granulocyte/macrophage colony-stimulating factor (GM-MDM).

Clinical Evolution of New Delhi Metallo-β-Lactamase (NDM) Optimizes Resistance under Zn(II) Deprivation.

Carbapenem-resistant (CRE) are rapidly spreading and taking a staggering toll on all health care systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family of carbapenemases are the Zn(II)-dependent β-lactamases, known as metallo-β-lactamases (MBLs). Among them, the New Delhi metallo-β-lactamase (NDM) has experienced the fastest and widest geographical spread.

Immunomodulatory effects of heat-killed Mycobacterium obuense on human blood dendritic cells.

Heat-killed (HK) Mycobacterium obuense is a novel immunomodulator, currently undergoing clinical evaluation as an immunotherapeutic agent in the treatment of cancer. Here, we examined the effect of in vitro exposure to HK M. obuense on the expression of different categories of surface receptors on human blood myeloid (m) and plasmacytoid (p) DCs.

Differential regulation of surface receptor expression, proliferation, and apoptosis in HaCaT cells stimulated with interferon-γ, interleukin-4, tumor necrosis factor-α, or muramyl dipeptide.

Keratinocytes are routinely subjected to both internal and external stimulation. This study investigates the effects of interferon gamma, interleukin-4, tumor necrosis factor alpha, and the synthetic immunomodulator muramyl dipeptide on the human keratinocyte cell line, HaCaT. Following HaCaT stimulation with cytokines or muramyl dipeptide for different time periods, changes in the expression of different cell surface receptors, cell proliferation, and cell apoptosis were evaluated by flow cytometry, tritiated thymidine uptake, and annexin-V staining, respectively.

Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase.

Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form.

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers.

Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-β-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases.

Analysis of the immunomodulatory properties of two heat-killed mycobacterial preparations in a human whole blood model.

The significant role played by mycobacteria in modulating immune responses through enhancing the crosstalk between innate and adaptive immunity has been highlighted in several studies. Owing to their unique antigenic profile, heat killed (HK) preparations of rapid-growing mycobacteria, currently undergoing clinical development, have been assessed as adjuvant therapy in various diseases. The purpose of this study is to investigate the regulation of leukocyte surface receptors, in whole blood from healthy donors, following in vitro stimulation with HK Mycobacterium vaccae (M.