Development of CGS-15943 Adjunctives for the Disruption of Plasmid Maintenance in Multidrug Resistant .

Carbapenemase producing (CPEs) represent a group of multidrug resistant pathogens for which few, if any, therapeutics options remain available. CPEs generally harbor plasmids that encode resistance to last resort carbapenems and many other antibiotics. We previously performed a high throughput screen to identify compounds that can disrupt the maintenance and replication of resistance conferring plasmids through use of a synthetic screening plasmid introduced into K-12 cells.

State Medicaid Policies Governing Access to Medications for Opioid Use Disorder (MOUD) and MOUD Treatment Use in a Large Sample of People Who Inject Drugs in 20 U.S. States.

Background: People who inject drugs (PWID) are especially vulnerable to harms from opioid use disorder (OUD). Medications for OUD (MOUD) effectively reduce overdose and infectious disease transmission risks.

Objective: We investigate whether state Medicaid coverage for methadone and buprenorphine is related to past-year MOUD use among PWID using cross-sectional, multilevel analyses with individual-level data on PWID from the Centers for Disease Control and Prevention's 2018 National HIV Behavioral Surveillance.

Idiopathic non-mast cell angioedema: Treatment insights from global experts.

Idiopathic non-mast cell angioedema (INMA) is a rare disease typified by recurrent attacks of cutaneous and subcutaneous swelling. Every attack carries the potential for severe morbidity and, in the case of laryngeal involvement, mortality. Whereas therapies approved for hereditary angioedema (HAE) have been used in the care of patients with INMA, little is known with regard to their efficacy for the treatment of this disease.

Appraisal of the evidence linking hereditary α-tryptasemia with mast cell disorders, hypermobility and dysautonomia.

Since its first description more than a decade ago, our understanding of the clinical impact of hereditary alpha-tryptasemia has continued to evolve. First considered to be a genetic disorder with a subset of patients having a syndromic presentation composed of connective tissue abnormalities, symptoms of autonomic dysfunction, and findings of mast cell activation, we now know that hereditary alpha-tryptasemia is a common genetic trait and modifier of mast cell-mediated reactions. More recent studies have shown some previously held associations with congenital hypermobility and postural orthostatic tachycardia syndrome (POTS) to be lacking, and illuminated previously unappreciated associations with clonal and nonclonal mast cell disorders.

Systematic review of omalizumab for refractory clonal and non-clonal mast cell activation syndrome.

Patients with mast cell activation syndrome (MCAS) can be refractory to standard antimediator therapy. Alternative treatment options to reduce disease burden and improve quality of life are needed. To compile the evidence that supports the use of omalizumab for patients with refractory MCAS.

Evaluation of allergic diseases in children diagnosed with cutaneous mastocytosis.

Cutaneous mastocytosis (CM) is the most common type of mastocytosis in children. The atopy frequency in these patients is typically similar to that in the general population, but a higher incidence of anaphylaxis is reported. This study aimed to evaluate the presence of allergic diseases in children diagnosed with CM and its impact on clinical manifestations.

Clinical remission in patients with severe eosinophilic asthma treated with mepolizumab: A analysis of RELIght study.

Remission of asthma can occur as part of the natural history of the disease; however, the use of biologics can result in disease remission in some patients. In this post hoc analysis of the RELIght study, we aimed to evaluate clinical remission in real life among patients treated with mepolizumab, to detect possible differences between "remitters" and "nonremitters," and to evaluate possible predictors of remission. Clinical remission was defined as the absence of asthma exacerbations, discontinuation of oral corticosteroids (OCS), achievement of asthma control (Asthma Control Test [ACT] ≥ 20), and stable or improved lung function.

Relationship between triglyceride levels and different snoring states: a systematic review and meta-analysis.

Objective: High triglyceride (TG) levels are important risk factors for cardiovascular disease (CVD). Some recent studies have shown that snoring is also closely related to elevated TG levels. The specific pathogenesis of elevated TG levels in snoring patients is still unclear.

Effects of stress hyperglycemia ratio upon long-lasting prognosis in coronary artery disease patients with or lacking chronic renal impairment: findings from a Chinese multi-center observational study.

Background: Lately, numerous researches have portrayed stress hyperglycemia ratio (SHR) is predominantly connected with short-term adverse prognosis among individuals who have acute coronary syndrome. Nevertheless, the relation of SHR with prolonged effects and the value of SHR in predicting in coronary artery disease (CAD) patients with or lacking chronic kidney disease (CKD) remain unclear. The present study was designed to elucidate the relation of SHR with prolonged prognosis and the value of SHR in predicting the long-term all-cause and cardiovascular death of CAD patients with CKD or non-CKD.

Active games for increasing social and emotional competencies of young adults in probation system: a one-sample trial study in Izmir city in Turkiye.

Introduction: The prevalence of substance use among young adults has been increasing in Turkiye. Probation as a form of execution continues to grow in popularity around the world, as it has the potential for more successful outcomes than closed institutional execution methods. However, in the face of changing societal and individual needs, the probation system must rapidly adapt to current public realities, especially with new approaches, including the use of purposeful physical movement for young adults who are obliged due to illegal substance use.

Comparison of baseline global gene expression profiles of prostate cancer cell lines LNCaP and DU145.

Introduction: DU145 and LNCaP are classic prostate cancer cell lines. Characterizing their baseline transcriptomics profiles (without any intervention) can offer insights into baseline genetic features and oncogenic pathways that should be considered while interpreting findings after various experimental interventions such as exogenous gene transfection or drug treatment.

Methods: LNCaP and DU145 cell lines were cultured under normal conditions, followed by RNA extraction, cDNA conversion, library preparation, and RNA sequencing using the Illumina NovaSeq platform.

Alarmins and their pivotal role in the pathogenesis of spontaneous abortion: insights for therapeutic intervention.

Alarmins are a class of molecules released when affected cells damaged or undergo apoptosis. They contain various chemotactic and immunomodulatory proteins or peptides. These molecules regulate the immune response by interacting with pattern recognition receptors (PRRs) and play important roles in inflammatory response, tissue repair, infection defense, and cancer treatment.

Screening sites for detection of carbapenemase-producers- a retrospective cohort study.

While screening the rectal site and urine may be appropriate for detection of carbapenemase-producing Enterobacterales, respiratory samples, throat and wound swabs may increase the sensitivity of screening protocols when aiming to detect colonization with carbapenemase-producing non-fermenting bacteria. Our results support the need for tailoring screening recommendations according to the bacterial species targeted.

The powerless bosses: the working day experience of bicycle messengers and its impact on their identities and wellbeing.

Background: Bicycle messengers in the online food delivery sector typically work on an on-demand basis, have digitally mediated relationships with their employer, and have very limited labor rights. In this study, we explore how bicycle messengers themselves experience their workday and how platform work influences their identity and wellbeing.

Method: We conducted qualitative interviews with ten bicycle messengers working for Foodora and Wolt in Bergen and Oslo, Norway.

Genomic Patterns are Associated with Different Sequelae of Patients with Long-Term COVID-19.

In the post-large era, various COVID-19 sequelae are getting more and more attention to health problems. Although the mortality rate of the COVID-19 infection is now declining, it is often accompanied by new clinical sequelae with different symptoms such as fatigue after infection, loss of smell. The degree of age, gender, virus infection seems to be weakly correlated with clinical symptoms.

Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.

Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.

Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.

Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.

Patient-derived response estimates from zero-passage organoids of luminal breast cancer.

Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.

Health checks for autistic adults: study protocol for a cluster randomised controlled trial.

Background: Autistic people commonly have physical and mental health conditions. They also frequently experience barriers to accessing healthcare, contributing to problems identifying and treating health conditions. These factors may lead to increased and earlier morbidity and lower average life expectancy for autistic people.

The efficacy of platelet-rich plasma in ankle disease: a systematic review and meta-analysis.

Objective: Ankle osteoarthritis is a debilitating condition that significantly impairs patients' quality of life. Platelet-rich plasma has emerged as a novel cellular therapy in clinical practice. This study evaluates the clinical efficacy of platelet-rich plasma (PRP) after intervention in ankle disorders, so as to provide strong evidence in support of clinical treatment.

Chili pepper consumption and duration of fissure symptoms onset are associated with perianal fistula development among patients with anal fissure: a case-control study.

Background: Perianal fistula is one of the complications of deepened anal fissure. The present case-control study aimed to assess the risk factors of fissure-associated fistulas due to the limited available evidence.

Methods: Patients with fissure-associated fistulas were considered as case, and patients with anal fissure who were undergoing medical treatment without any previous anorectal surgeries were considered as control group.

GRK6 palmitoylation dictates triple-negative breast cancer metastasis via recruiting the β-Arrestin 2/MAPKs/NF-κB signaling axis.

Background: Triple negative breast cancer (TNBC) belongs to the worst prognosis of breast cancer subtype probably because of distant metastasis to other organs, e.g. lungs.

Association of continuous renal replacement therapy downtime with fluid balance gap and clinical outcomes: a retrospective cohort analysis utilizing EHR and machine data.

Background: Fluid balance gap (FBgap-prescribed vs. achieved) is associated with hospital mortality. Downtime is an important quality indicator for the delivery of continuous renal replacement therapy (CRRT).

A case of subcutaneous metastatic malignant melanoma of the left medial ankle: a case report and review of literature.

Background: Although rare, melanoma confined to the dermis or subcutaneous tissue without evidence of a primary cutaneous site should provoke consideration of melanoma of unknown primary. This diagnosis carries a favorable prognosis when compared with cutaneous metastatic melanoma. Several hypotheses have been proposed for how melanoma of unknown primary develops, two of which were considered in our patient case: (1) spontaneous regression of the primary tumor following metastasis or (2) the traumatic implantation of ectopic melanocytic cells in other tissues, such as the subcutaneous tissue.