Nutraceuticals silybin B, resveratrol, and epigallocatechin-3 gallate-bind to cardiac muscle troponin to restore the loss of lusitropy caused by cardiomyopathy mutations , , and .

Introduction: Adrenergic activation of protein kinase A (PKA) in cardiac muscle targets the sarcolemma, sarcoplasmic reticulum, and contractile apparatus to increase contractile force and heart rate. In the thin filaments of the contractile apparatus, cardiac troponin I (cTnI) Ser22 and Ser23 in the cardiac-specific N-terminal peptide (NcTnI: residues 1 to 32) are the targets for PKA phosphorylation. Phosphorylation causes a 2-3 fold decrease of affinity of cTn for Ca associated with a higher rate of Ca dissociation from cTnC leading to a faster relaxation rate of the cardiac muscle (lusitropy).

Is arbuscular mycorrhizal fungal addition beneficial to potato systems? A meta-analysis.

The application of arbuscular mycorrhizal (AM) fungi has been reported to confer multiple agronomic benefits to crop plants including cereals, vegetables, and fruit trees, as well as to improve soil structure and health. In this study, we conducted a meta-analysis to investigate whether AM fungal addition enhances potato yield. We further examined whether several experimental conditions (type of experiment, inoculation method, and source of AM fungi) and potato cultivar may explain the outcomes.

The mycobacterium lipid transporter MmpL3 is dimeric in detergent solution, SMALPs and reconstituted nanodiscs.

The mycobacterial membrane protein large 3 (MmpL3) transports key precursor lipids to the outer membrane of Mycobacterium species. Multiple structures of MmpL3 from both and in various conformational states indicate that the protein is both structurally and functionally monomeric. However, most other resistance, nodulation and cell division (RND) transporters structurally characterised to date are either dimeric or trimeric.

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

Introduction: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction.

First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation.

Background And Objectives: In spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by desired therapeutic plasma concentration, there is lack of equivalent means of determining dose delivery in SCS. In open-loop (OL) SCS, due to the dynamic nature of the epidural space, the activating electric field delivered is inconsistent at the level of the dorsal columns.

Methods for SARS-CoV-2 hospital disinfection, observations.

Introduction: Escalation of chemical disinfection during the COVID-19 pandemic has raised occupational hazard concerns. Alternative and potentially safer methods such as ultraviolet-C (UVC) irradiation and ozone have been proposed, notwithstanding the lack of standardized criteria for their use in the healthcare environment.

Aim: Compare the virucidal activity of 70% ethanol, sodium dichloroisocyanurate (NaDCC), chlorhexidine, ozonated water, UVC-222 nm, UVC-254 nm against three SARS-CoV-2 variants of concern cultured .

Modulation of Structure and Dynamics of Cardiac Troponin by Phosphorylation and Mutations Revealed by Molecular Dynamics Simulations.

Adrenaline acts on β1 receptors in the heart muscle to enhance contractility, increase the heart rate, and increase the rate of relaxation (lusitropy) via activation of the cyclic AMP-dependent protein kinase, PKA. Phosphorylation of serines 22 and 23 in the N-terminal peptide of cardiac troponin I is responsible for lusitropy. Mutations associated with cardiomyopathy suppress the phosphorylation-dependent change.

Identification of antibiotic consumption targets for the management of infection in hospitals- a threshold logistic modelling approach.

Background: This study aims to demonstrate the utility of a threshold logistic approach to identifying thresholds for specific antibiotic use associated with Clostridioides difficile infection (CDI) in an English teaching hospital.

Methods: A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to identify thresholds and risk scores in hospital-level antibiotic use associated with hospital-onset, healthcare-associated (HOHA) CDI cases.

Results: Using a threshold logistic regression approach, an incidence greater than 0.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

Introduction: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant.

Methods: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS.

Laboratory Surveillance, Quality Management, and Its Role in Addressing Antimicrobial Resistance in Africa: A Narrative Review.

AMR is a major public health concern that calls for extensive work and a multidisciplinary team approach. The high prevalence of infectious diseases in African nations leads to widespread antibiotic usage and eventual antimicrobial resistance, which has significant negative effects on people's health, the economy, and society. Additionally, inadequate or nonexistent antimicrobial drug regulations, inappropriate prescription practices, and restrictions on public health prevention initiatives such as immunization, water and sanitation, and sexual health may all contribute to the emergence of AMR.

Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.

Purpose: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis.

Experimental Design: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible.

Chlorhexidine Resistance or Cross-Resistance, That Is the Question.

Chlorohexidine (CHX) is a widely used biocide in clinical and household settings. Studies over the last few decades have reported CHX resistance in different bacterial species, but at concentrations well below those used in the clinical setting. Synthesis of these findings is hampered by the inconsistent compliance with standard laboratory procedures for biocide susceptibility testing.

Meta-analysis of global soil data identifies robust indicators for short-term changes in soil organic carbon stock following land use change.

The restoration of degraded lands and minimizing the degradation of productive lands are at the forefront of many environmental land management schemes around the world. A key indicator of soil productivity is soil organic carbon (SOC), which influences the provision of most soil ecosystem services. A major challenge in direct measurement of changes in SOC stock is that it is difficult to detect within a short timeframe relevant to land managers.

Evaluation of emerging NASH therapies: the impact of treatment efficacy profiles on long-term health outcomes.

Evaluations of nonalcoholic steatohepatitis (NASH) treatments require predicting lifetime outcomes from short-term clinical trials. A Markov model with NASH fibrosis stages F0-F3, NASH resolution, compensated cirrhosis (F4/CC), and liver-related complication (LRC) states was developed using literature-based standard of care (SoC) data. Hypothetical efficacy profiles were defined affecting resolution (100%-increase), fibrosis improvement (100% increase), or fibrosis worsening (50% decrease).

Kinetics and Mechanisms of Hydrothermal Dehydration of Cyclic 1,2- and 1,4-Diols.

Hydrothermal dehydration is an attractive method for deoxygenation and upgrading of biofuels because it requires no reagents or catalysts other than superheated water. Although mono-alcohols cleanly deoxygenate via dehydration under many conditions, polyols such as those derived from saccharides and related structures are known to be recalcitrant with respect to dehydration. Here, we describe detailed mechanistic and kinetic studies of hydrothermal dehydration of 1,2- and 1,4-cyclohexanediols as model compounds to investigate how interactions between the hydroxyls can control the reaction.

Large-Scale Distributed Training of Transformers for Chemical Fingerprinting.

Transformer models have become a popular choice for various machine learning tasks due to their often outstanding performance. Recently, transformers have been used in chemistry for classifying reactions, reaction prediction, physiochemical property prediction, and more. These models require huge amounts of data and localized compute to train effectively.

Response: Sometimes we wish Chris and Sam had died of cancer! - a response to Commentaries on the May 2022 Debate.

The debate articles in CAMH Journal, May 2022, have received some responses from contributors who are well known for their anti-diagnosis views concerning borderline personality disorder (BPD). Within these responses, we had hoped to see these campaigners try to test their worldview against our tragic experiences but we have been sadly disappointed. Our daughters actually lived in the world these campaigners hope to construct: a world where professionals behave as if BPD does not exist, a world where NICE Guidance for BPD is therefore entirely ignored.

Identifying Targets for Antibiotic Use for the Management of Carbapenem-Resistant (CRAb) in Hospitals-A Multi-Centre Nonlinear Time-Series Study.

Solutions are needed to inform antimicrobial stewardship (AMS) regarding balancing the access to effective antimicrobials with the need to control antimicrobial resistance. Theoretical and mathematical models suggest a non-linear relationship between antibiotic use and resistance, indicating the existence of thresholds of antibiotic use beyond which resistance would be triggered. It is anticipated that thresholds may vary across populations depending on host, environment, and organism factors.

Modulation of cardiac thin filament structure by phosphorylated troponin-I analyzed by protein-protein docking and molecular dynamics simulation.

Tropomyosin, controlled by troponin-linked Ca-binding, regulates muscle contraction by a macromolecular scale steric-mechanism that governs myosin-crossbridge-actin interactions. At low-Ca, C-terminal domains of troponin-I (TnI) trap tropomyosin in a position on thin filaments that interferes with myosin-binding, thus causing muscle relaxation. Steric inhibition is reversed at high-Ca when TnI releases from F-actin-tropomyosin as Ca and the TnI switch-peptide bind to the N-lobe of troponin-C (TnC).

Debate: "The-Diagnosis-That-Must-Not-Be-Named" - Professionals' fear of BPD is failing their patients.

Borderline personality disorder (BPD) in Child and Adolescent Mental Health Services (CAMHS) seems to be the "Voldemort Diagnosis" - it must not be named! We believe this is misguided and dangerous. Failure to inform patients and carers of the potential for this diagnosis disempowers them. Everyone has a right to research and understand their own condition.

Lipid21: Complex Lipid Membrane Simulations with AMBER.

We extend the modular AMBER lipid force field to include anionic lipids, polyunsaturated fatty acid (PUFA) lipids, and sphingomyelin, allowing the simulation of realistic cell membrane lipid compositions, including raft-like domains. Head group torsion parameters are revised, resulting in improved agreement with NMR order parameters, and hydrocarbon chain parameters are updated, providing a better match with phase transition temperature. Extensive validation runs (0.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain: A Secondary Analysis of the Evoke Randomized Clinical Trial.

Importance: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system.

The evolution of ICER's review process for new medical interventions and a critical review of economic evaluations (2018-2019): how stakeholders can collaborate with ICER to improve the quality of evidence in ICER's reports.

Since its inception in 2006, the Institute for Clinical and Economic Review (ICER) has rapidly gained influence on drug pricing and reimbursement decisions despite historical resistance to the use of cost-effectiveness thresholds in the US health care system. Although patient groups, physicians, and pharmaceutical manufacturers voiced their concerns about the potential negative effects of increased use of ICER's assessments on patient access to innovative medications, there is little guidance and consensus on how the stakeholders should collaborate with ICER to ensure that its reviews reflect the best clinical and economic evidence. To (1) summarize the evolution of ICER's evaluation procedure, scope, and topics; (2) evaluate the effectiveness of stakeholder engagement approaches; and (3) inform stakeholders of their potential role in collaborating with ICER in estimating the cost-effectiveness of new interventions.

Antimicrobial Synergy Testing: Comparing the Tobramycin and Ceftazidime Gradient Diffusion Methodology Used in Assessing Synergy in Cystic Fibrosis-Derived Multidrug-Resistant .

The need for synergy testing is driven by the necessity to extend the antimicrobial spectrum, reducing drug dosage/toxicity and the development of resistance. Despite the abundance of synergy testing methods, there is the absence of a gold standard and a lack of synergy correlation among methods. The most popular method (checkerboard) is labor-intensive and is not practical for clinical use.