Pharmacologically enabling the degradation of NaV1.8 channels to reduce neuropathic pain.

In phase II clinical trials, NaV1.8 channels were identified as viable targets to treat acute pain. Results were modest, however, and NaV1.

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.

A deep-sea isopod that consumes sinking from the ocean's surface.

Most deep-ocean life relies on organic carbon from the surface ocean. While settling primary production rapidly attenuates in the water column, pulses of organic material can be quickly transported to depth in the form of food falls. One example of fresh material that can reach great depths across the tropical Atlantic Ocean and Caribbean Sea is the pelagic macroalgae .

Identifying the function of the NMDA NR1 subunit through its interaction with Magi-2 during inflammatory pain.

Much is understood about the structure and gating properties of NMDA receptors (NMDAR), but the function of the carboxy-terminal splice variant of the NR1 subunit, NR1 has never been identified. By studying the scaffolding protein Magi-2 in animal models of inflammatory pain, we discovered how NR1 protein is specifically regulated. We found that Magi-2 deficiency resulted in decreased pain behavior and a concomitant reduction in NR1 protein.

Distinct Inflammatory Phenotypes Are Associated With Subclinical and Clinical Cardiovascular Disease in People With Human Immunodeficiency Virus.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in 2 independent cohorts of PWH.

Post-COVID care delivery: The experience from an Irish tertiary centre's post-COVID clinic.

Background: The long-term effects of SARS-CoV-2 infection and optimal follow-up approach are not well-recognised. Here we describe the implementation of a post-COVID clinic in an Irish tertiary centre after the first wave of the pandemic. This study describes the characteristics of our patient cohort and the operations and outcomes of the clinic, exploring some of the risk factors for developing post-COVID syndrome and the appropriateness of the triage system employed.

Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil's Antimicrobial Response by Engaging the Histamine 2 Receptor.

We found that histamine (10-9 M) did not have any effect on the in vitro capture of Escherichia coli by neutrophils but accelerated its intracellular killing. In contrast, histamine (10-6 M) delayed the capture of Escherichia coli by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H4R and the H2R, which are coupled to the Src family tyrosine kinases or the cAMP/protein kinase A pathway, respectively.

Microbial Consortia and Mixed Plastic Waste: Pangenomic Analysis Reveals Potential for Degradation of Multiple Plastic Types via Previously Identified PET Degrading Bacteria.

The global utilization of single-use, non-biodegradable plastics, such as bottles made of polyethylene terephthalate (PET), has contributed to catastrophic levels of plastic pollution. Fortunately, microbial communities are adapting to assimilate plastic waste. Previously, our work showed a full consortium of five bacteria capable of synergistically degrading PET.

E-cigarette Use and Disease Outcomes in Inflammatory Bowel Diseases: A Case-Control Study.

Introduction: Traditional cigarette use adversely impacts disease outcomes in Crohn's disease (CD). There has been a worldwide increase in the use of e-cigarettes over the past decade. The impact of use of nicotine containing e-cigarettes on disease outcomes in CD or ulcerative colitis (UC) has not been well defined.

: The Versatile Host for Drug Discovery, In Vivo Toxicity Testing and Characterising Host-Pathogen Interactions.

Larvae of the greater wax moth, , are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to pathogens and provide results similar to those from mammals. larvae are now widely used in academia and industry and their use can assist in the identification and evaluation of novel antimicrobial agents. larvae are inexpensive to purchase and house, easy to inoculate, generate results within 24-48 h and their use is not restricted by legal or ethical considerations.

Thermal hyperalgesia and dynamic weight bearing share similar recovery dynamics in a sciatic nerve entrapment injury model.

Chronic constriction injuries (CCI) of the sciatic nerve are widely used nerve entrapment animal models of neuropathic pain. Two common pain behaviors observed following CCI are thermal hyperalgesia and mechanical allodynia, measured by the Hargreaves and von Frey tests, respectively. While thermal hyperalgesia tends to recover by 30 days, mechanical allodynia can persist for many more months thereafter.

Multi-targeted metallo-ciprofloxacin derivatives rationally designed and developed to overcome antimicrobial resistance.

Antimicrobial resistance is a major global threat to human health due to the rise, spread and persistence of multi-drug-resistant bacteria or 'superbugs'. There is an urgent need to develop novel chemotherapeutics to overcome this overarching challenge. The authors derivatized a clinically used fluoroquinolone antibiotic ciprofloxacin (Cip), and complexed it to a copper phenanthrene framework.

Inhibiting endocytosis in CGRP nociceptors attenuates inflammatory pain-like behavior.

The advantage of locally applied anesthetics is that they are not associated with the many adverse effects, including addiction liability, of systemically administered analgesics. This therapeutic approach has two inherent pitfalls: specificity and a short duration of action. Here, we identified nociceptor endocytosis as a promising target for local, specific, and long-lasting treatment of inflammatory pain.

Rapid and Laboratory SARS-CoV-2 Antibody Testing in High-Risk Hospital Associated Cohorts of Unknown COVID-19 Exposure, a Validation and Epidemiological Study After the First Wave of the Pandemic.

We aimed to use SARS-CoV-2 antibody tests to assess the asymptomatic seroprevalence of individuals in high-risk hospital cohorts who's previous COVID-19 exposure is unknown; staff, and patients requiring haemodialysis or chemotherapy after the first wave. In a single Center, study participants had five SARS-CoV-2 antibody tests done simultaneously; one rapid diagnostic test (RDT) (Superbio Colloidal Gold IgM/IgG), and four laboratory tests (Roche Elecsys® Anti-SARS-CoV-2 IgG [RE], Abbott Architect i2000SR IgG [AAr], Abbott Alinity IgG [AAl], and Abbott Architect IgM CMIA). To determine seroprevalence, only positive test results on laboratory assay were considered true positives.

Yield and Predictors of Surveillance Colonoscopies in Older Adults With Long-standing Ulcerative Colitis.

Background & Aims: Although colonoscopies for dysplasia surveillance are standard of care in patients with long-standing ulcerative colitis (UC), there is a paucity of data on the yield of surveillance colonoscopies in those older than 75 years of age.

Methods: We conducted a multicenter retrospective cohort study including patients with UC who underwent ≥1 colonoscopy at age ≥75 years. The primary outcome was diagnosis of dysplasia (visible or random) and colorectal cancer.

False detection of rifampicin resistance using Xpert MTB/RIF Ultra assay due to an A451V mutation in .

Background: In a 12 month period, three Irish-born adult cases with pulmonary TB were initially diagnosed by Xpert MTB/RIF Ultra assay, which detected a rifampicin resistance-conferring mutation prompting treatment as potential MDR cases.

Methods: Further laboratory investigations on the cultured isolates included GenoType MTBDR assay, phenotypic drug susceptibility tests using the BD BACTEC MGIT culture system and MIC broth microdilution tests. Sequencing of the gene was performed using Sanger sequencing and WGS.

Antibiotic prescribing patterns in patients hospitalized with COVID-19: lessons from the first wave.

Background: A high proportion of hospitalized patients with COVID-19 receive antibiotics despite evidence to show low levels of true bacterial coinfection.

Methods: A retrospective cohort study examining antibiotic prescribing patterns of 300 patients sequentially diagnosed with COVID-19. Patients were grouped into 3 sub-cohorts: Group 1 received no antibiotics, Group 2 received antibiotics for microbiologically confirmed infections and Group 3 was empirically treated with antibiotics for pneumonia.

Documentation of Do-Not-Attempt-Cardiopulmonary-Resuscitation orders amid the COVID-19 pandemic.

Introduction: the COVID-19 pandemic has brought the decision-making process regarding cardiopulmonary resuscitation (CPR) into focus. The aim of this study is to compare rates of Do-Not-Attempt-CPR (DNACPR) documentation in older hospitalised patients before and during the COVID-19 pandemic.

Methods: this was a retrospective repeated cross-sectional study.

A multidisciplinary evaluation of suspected, non-confirmed cases of COVID-19 including chest CT, as compared to World Health Organization recommendations.

Aim: To report an audit of the evaluation of suspected, unconfirmed cases of COVID-19 including chest computed tomography (CT), as compared to World Health Organization recommendations.

Methods: A clinical audit was undertaken examining the evaluation of patients with suspected COVID-19 with negative SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, with comparison to WHO recommendations. A retrospective chart review was undertaken for 90 patients examining investigations, in particular CT, used to clarify the diagnosis.

Proteomic profiling of bacterial and fungal induced immune priming in Galleria mellonella larvae.

Some insects display immunological priming as a result of elevated humoral and cellular responses which give enhanced survival against subsequent infection. The humoral immune response of Galleria mellonella larvae following pre-exposure to heat killed Staphylococcus aureus or Candida albicans cells was determined by quantitative mass spectrometry in order to assess the relationship between the humoral immune response and resistance to subsequent bacterial or fungal infection. Larvae pre-exposed to heat killed S.

Innate Immune Responses of to BCG Challenge Identified Using Proteomic and Molecular Approaches.

The larvae of the insect , have recently been established as a non-mammalian infection model for the complex (MTBC). To gain further insight into the potential of this model, we applied proteomic (label-free quantification) and transcriptomic (gene expression) approaches to characterise the innate immune response of to infection with BCG over a 168 h time course. Proteomic analysis of the haemolymph from infected larvae revealed distinct changes in the proteome at all time points (4, 48, 168 h).

UtilisingGalleria mellonella larvae for studying in vivo activity of conventional and novel antimicrobial agents.

The immune response of insects displays many structural and functional similarities to the innate immune response of mammals. As a result of these conserved features, insects may be used for evaluating microbial virulence or for testing the in vivo efficacy and toxicity of antimicrobial compounds and results show strong similarities to those from mammals. Galleria mellonella larvae are widely used in this capacity and have the advantage of being easy to use, inexpensive to purchase and house, and being free from the ethical and legal restrictions that relate to the use of mammals in these tests.