Respiratory Health Associated With Systemic Metal Exposure in Post-9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

Objective: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals.

Methods: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking.

Self-reported respiratory outcomes associated with blast exposure in post 9/11 veterans.

Background: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001.

Does the pollution halo hypothesis exist in this "better" world? The evidence from STIRPAT model.

Multinational corporation has changed their host countries. The new wave of FDI inflow attracted the interest of policymakers. FDI has significant effects on both productivity and carbon dioxide emissions.

Trends in Moral Injury, Distress, and Resilience Factors among Healthcare Workers at the Beginning of the COVID-19 Pandemic.

The coronavirus severe acute respiratory syndrome (COVID-19) pandemic has placed increased stress on healthcare workers (HCWs). While anxiety and post-traumatic stress have been evaluated in HCWs during previous pandemics, moral injury, a construct historically evaluated in military populations, has not. We hypothesized that the experience of moral injury and psychiatric distress among HCWs would increase over time during the pandemic and vary with resiliency factors.

Acupressure for labor pain management: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the efficacy/effectiveness of acupressure as an adjunct to standard procedures during labor and delivery, compared with standard procedures with/without sham acupressure, in randomized controlled trials (RCTs).

Methods: Ten main databases were searched from their inception until 31 January 2018. Two reviewers independently extracted data concerning the effects of acupressure on pain intensity, labor duration, mode of delivery, use of medications and adverse events.

Signaling specificity in the c-di-GMP-dependent network regulating antibiotic synthesis in Lysobacter.

Enzymes controlling intracellular second messengers in bacteria, such as c-di-GMP, often affect some but not other targets. How such specificity is achieved is understood only partially. Here, we present a novel mechanism that enables specific c-di-GMP-dependent inhibition of the antifungal antibiotic production.

Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.

C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP.

Structural Insights into the Distinct Binding Mode of Cyclic Di-AMP with SaCpaA_RCK.

Cyclic di-AMP (c-di-AMP) is a relatively new member of the family of bacterial cyclic dinucleotide second messengers. It has attracted significant attention in recent years because of the abundant roles it plays in a variety of Gram-positive bacteria. The structural features that allow diverse bacterial proteins to bind c-di-AMP are not fully understood.

Effect of administration of neuromuscular blocking agents in children with severe traumatic brain injury on acute complication rates and outcomes: a secondary analysis from a randomized, controlled trial of therapeutic hypothermia.

Objective: To evaluate the association between neuromuscular blocking agents and outcome, intracranial pressure, and medical complications in children with severe traumatic brain injury.

Design: A secondary analysis of a randomized, controlled trial of therapeutic hypothermia.

Setting: Seventeen hospitals in the United States, Australia, and New Zealand.

Backbone resonance assignments of the 54 kDa dimeric C-terminal domain of murine STING in complex with DMXAA.

The mammalian ER protein STING (stimulators of interferon genes) is an important innate immunity protein for linking detection of novel secondary messengers c-di-GMP, c-di-AMP, cGAMP or cytosolic dsDNA to the activation of TANK kinase 1 and its downstream interferon regulator factor 3. Recently quite a few of crystal structures representing different states of the C-terminal domain (CTD) of human and murine STING (hSTING and mSTING) in complex with c-di-GMP, cGAMP or DMXAA have been reported. However, the C-terminal 42 residues of STING-CTD, which may be important in mediating the downstream reactions, is invisible or absent in all reported X-ray structures.

Crystallization of the N-terminal regulatory domain of the enhancer-binding protein FleQ from Stenotrophomonas maltophilia.

FleQ is a master regulator that controls bacterial flagellar gene expression. It is a unique enhancer-binding protein or repressor protein comprising an N-terminal FleQ domain, an AAA(+)/ATPase σ54-interaction domain and a helix-turn-helix DNA-binding domain. FleN is a putative ATPase with a deviant Walker A motif that works together with FleQ by binding to the FleQ N-terminal domain to fully express pel, psl and cdr operons in the presence of c-di-GMP to enhance biofilm formation.

Effect of ethnicity, dietary intake and physical activity on plasma adiponectin concentrations among malaysian patients with type 2 diabetes mellitus.

Background: The Malaysian Health and morbidity Survey (2006) reported the highest prevalence of type 2 diabetes mellitus (T2DM) among the Indian population compared to the Malay and Chinese populations. Many studies have supported the important role of adiponectin in insulin-sensitizing, which is associated with T2DM. These studies have raised a research question whether the variation in prevalence is related to the adiponectin concentrations or the lifestyle factors.

Impact of telavancin on prothrombin time and activated partial thromboplastin time as determined using point-of-care coagulometers.

Telavancin is approved in the United States, Canada, and Europe (At the time of submission, the telavancin European marketing authorization for nosocomial pneumonia was suspended until Theravance provides evidence of a new European Medicines Agency approved supplier) as an antibiotic to treat certain Gram-positive bacterial skin infections. Telavancin has been shown to prolong plasmatic prothrombin (PT) and activated partial thromboplastin (aPTT) clotting times in clinical diagnostic lab-based assays. In this study, we evaluated the potential for telavancin to prolong whole blood PT/International Normalized Ratio (INR) and aPTT tests on point-of-care (POC) instruments.

A cyclic GMP-dependent signalling pathway regulates bacterial phytopathogenesis.

Cyclic guanosine 3',5'-monophosphate (cyclic GMP) is a second messenger whose role in bacterial signalling is poorly understood. A genetic screen in the plant pathogen Xanthomonas campestris (Xcc) identified that XC_0250, which encodes a protein with a class III nucleotidyl cyclase domain, is required for cyclic GMP synthesis. Purified XC_0250 was active in cyclic GMP synthesis in vitro.

Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING.

The mammalian ER protein STING (stimulator of interferon genes; also known as MITA, ERIS, MPYS or TMEM173) is an adaptor protein that links the detection of cytosolic dsDNA to the activation of TANK-binding kinase 1 (TBK1) and its downstream transcription factor interferon regulatory factor 3 (IFN3). Recently, STING itself has been found to be the direct receptor of bacterial c-di-GMP, and crystal structures of several human STING C-terminal domain (STING-CTD) dimers in the apo form or in complex with c-di-GMP have been published. Here, a novel set of structures of mouse STING-CTD (mSTING(137-344)) in apo and complex forms determined from crystals obtained under different crystallization conditions are reported.

Crystallization and preliminary X-ray diffraction studies of Xanthomonas campestris PNPase in the presence of c-di-GMP.

Bacterial polynucleotide phosphorylase (PNPase) is a 3'-5' processive exoribonuclease that participates in mRNA turnover and quality control of rRNA precursors in many bacterial species. It also associates with the RNase E scaffold and other components to form a multi-enzyme RNA degradasome machinery that performs a wider regulatory role in degradation, quality control and maturation of mRNA and noncoding RNA. Several crystal structures of bacterial PNPases, as well as some biological activity studies, have been published.

Structural polymorphism of c-di-GMP bound to an EAL domain and in complex with a type II PilZ-domain protein.

Cyclic di-GMP (c-di-GMP) is a novel secondary-messenger molecule that is involved in regulating a plethora of important bacterial activities through binding to an unprecedented array of effectors. Proteins with a canonical PilZ domain that bind c-di-GMP play crucial roles in regulating flagellum-based motility. In contrast, noncanonical type II PilZ domains that do not effectively bind c-di-GMP regulate twitching motility, which is dependent on type IV pili (T4P).

Crystallization studies of the murine c-di-GMP sensor protein STING.

The innate immune response is the first defence system against pathogenic microorganisms, and cytosolic detection of pathogen-derived DNA is believed to be one of the major mechanisms of interferon production. Recently, the mammalian ER membrane protein STING (stimulator of IFN genes; also known as MITA, ERIS, MPYS and TMEM173) has been found to be the master regulator linking the detection of cytosolic DNA to TANK-binding kinase 1 (TBK1) and its downstream transcription factor IFN regulatory factor 3 (IRF3). In addition, STING itself was soon discovered to be a direct sensor of bacterial cyclic dinucleotides such as c-di-GMP or c-di-AMP.

Crystallization and preliminary X-ray diffraction characterization of the XccFimX(EAL)-c-di-GMP and XccFimX(EAL)-c-di-GMP-XccPilZ complexes from Xanthomonas campestris.

c-di-GMP is a major secondary-messenger molecule in regulation of bacterial pathogenesis. Therefore, the c-di-GMP-mediated signal transduction network is of considerable interest. The PilZ domain was the first c-di-GMP receptor to be predicted and identified.

The structure and inhibition of a GGDEF diguanylate cyclase complexed with (c-di-GMP)(2) at the active site.

Cyclic diguanosine monophosphate (c-di-GMP) is a key signalling molecule involved in regulating many important biological functions in bacteria. The synthesis of c-di-GMP is catalyzed by the GGDEF-domain-containing diguanylate cyclase (DGC), the activity of which is regulated by the binding of product at the allosteric inhibitory (I) site. However, a significant number of GGDEF domains lack the RxxD motif characteristic of the allosteric I site.

An efficient technique for drainage of seromas after breast cancer surgery.

Seroma formation is a frequent sequelae following breast cancer surgery. Current methods for seroma drainage often involve repeated needle aspiration that requires multiple passes, and is time consuming. We describe a technique that uses a needle attached to a high vacuum wound drainage system.

A novel tetrameric PilZ domain structure from xanthomonads.

PilZ domain is one of the key receptors for the newly discovered secondary messenger molecule cyclic di-GMP (c-di-GMP). To date, several monomeric PilZ domain proteins have been identified. Some exhibit strong c-di-GMP binding activity, while others have barely detectable c-di-GMP binding activity and require an accessory protein such as FimX to indirectly respond to the c-di-GMP signal.

Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules.

We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptors.