Accuracy and technical characteristics of CYP2C19 point of care tests: a systematic review.

To assess the accuracy and technical characteristics of point of care tests (POCTs). Systematic review of primary studies, in any population or setting, that evaluated POCTs for detecting loss of function (LOF) alleles. Eleven studies provided accuracy data (eight Spartan; one Genomadix Cube; one GMEX; one Genedrive).

Tissue-specific effects of temperature and salinity on the cell cycle and apoptosis in the Nile Tilapia (Oreochromis niloticus).

The Nile Tilapia (Oreochromis niloticus) evolved in warm, freshwater rivers, but possesses a broad physiological tolerance to a range of environmental conditions. Due to this hardiness and resilience, this species has been successfully introduced to regions widely outside of its native range. Here, we examine the impact of temperature and salinity variation on this species at the sub-lethal level.

2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization).

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia.

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT.

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against .

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of in protective T cell responses to the intracellular bacterium in the female reproductive tract (FRT). Mice deficient in exhibited severe defects in their ability to control shedding from the FRT.

Population Pharmacokinetic Modeling and Determination of Individual Exposure to Avalglucosidase Alfa in Adolescent and Adult Patients With Late-Onset Pompe Disease: Analysis of Pooled Data From Phase I to III Clinical Trials.

Background: Pompe disease is a rare genetic disorder caused by a deficiency of a lysosomal enzyme called acid alpha-glucosidase and is classified into infantile and late-onset forms. Since 2006, an enzyme replacement therapy involving alglucosidase alfa has been available. In 2021, a new enzyme replacement therapy involving avalglucosidase alfa demonstrated improved clinical benefits.

Selective Csp-F Bond Functionalization with Lithium Iodide.

A highly efficient method for C-F bond functionalization of a broad variety of activated and unactivated aliphatic substrates with inexpensive lithium iodide is presented. Primary, secondary, tertiary, benzylic, propargylic and α-functionalized alkyl fluorides react in chlorinated or aromatic solvents at room temperature or upon heating to the corresponding iodides which are isolated in 91-99% yield. The reaction is selective for aliphatic monofluorides and can be coupled with nucleophilic iodide replacements to install carbon-carbon, carbon-nitrogen and carbon-sulfur bonds with high yields.

Criteria of slope and endogenous level for selection of matrix in the quantitation of endogenous compounds by LC-MS/MS.

Selection of the appropriate matrix for standard curve is critical for an accurate and sensitive biomarker method. Slope of a standard curve is the key factor for parallelism assessment between tested matrix and authentic matrix for LC-MS/MS assays. Here the authors have established slope criteria using a generic equation and endogenous level criteria for achieving assay sensitivity.

2021 White Paper on Recent Issues in Bioanalysis: TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness ( - Recommendations on Gene Therapy, Cell Therapy, Vaccine Assays; Immunogenicity of Biotherapeutics and Novel Modalities; Integrated Summary of Immunogenicity Harmonization).

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Copper(ii) ketimides in sp C-H amination.

Commercially available benzophenone imine (HN[double bond, length as m-dash]CPh) reacts with β-diketiminato copper(ii) -butoxide complexes [Cu]-O Bu to form isolable copper(ii) ketimides [Cu]-N[double bond, length as m-dash]CPh. Structural characterization of the three coordinate copper(ii) ketimide [MeNN]Cu-N[double bond, length as m-dash]CPh reveals a short Cu-N distance (1.700(2) Å) with a nearly linear Cu-N-C linkage (178.

Development of Rabbit Monoclonal Antibodies for Quantitation of Therapeutic Human Antibodies in Preclinical Non-Human Primate Studies.

During preclinical studies, there is a great need to develop monoclonal antibodies (mAbs) that are specific to human immunoglobulin (IgG), without binding to monkey IgG, to detect therapeutic human mAb in non-human primates. We took advantage of the latest rabbit B cell cloning technology to develop six unique rabbit anti-human IgG mAb clones for this purpose. These clones are capable of binding to both human IgG and Fab with high affinity without nonspecific binding to cynomolgus monkey IgG.

Using Organizational Philosophy to Create a Self-Sustaining Compensation Plan Without Harming Academic Missions.

Problem: Academic physician reimbursement has moved to productivity-based compensation plans. To be sustainable, such plans must be self-funding. Additionally, unless research and education are appropriately valued, faculty involved in these efforts will become disillusioned, yet revenue generation in these activities is less robust than for clinical care activities.

The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa.

Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation.

Immunotoxicology: fifty years of global scientific progress.

The Immunotoxicology Specialty Section of the Society of Toxicology (SOT) celebrated the 50(th) Anniversary of the SOT by constructing a poster to highlight the milestones of Immunotoxicology during that half-century period. This poster was assembled by an ad hoc committee and intertwines in words, citations, graphics, and photographs our attempts to capture a timeline reference of the development and progressive movement of immunotoxicology across the globe. This poster was displayed during the 50(th) Annual SOT Meeting in Washington DC in March, 2011.

One- and two-year outcomes and predictors of mortality following emergency laparotomy: a consecutive series from a United Kingdom teaching hospital.

Background: Data on outcomes of patients who underwent emergency laparotomy (EML) are limited. This prospective observational study examined aspects of inpatient care and outcomes following EML with a view to identifying predictors of mortality.

Methods: Data collected from consecutive inpatients who underwent EML in a UK teaching hospital over a 3-month period included perioperative physiology, treatment, morbidity, and mortality (30-day, in-hospital, 12-month, and 24-month).

Antibacterial agent triclosan suppresses RBL-2H3 mast cell function.

Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis.

Negotiated dying: a grounded theory of how nurses shape withdrawal of treatment in hospital critical care units.

Background: The process of withdrawal of treatment in critical care environments has created ethical and moral dilemmas in relation to end of life care in the UK and elsewhere. Common within this discourse is the differing demands made on health professionals as they strive to provide care for the dying patient and family members. Despite reports that withdrawal of treatment is a source of tension between those nurses and doctors involved in the process, the role of the nurse in facilitating withdrawal of treatment has received relatively little attention.

Inorganic arsenite inhibits IgE receptor-mediated degranulation of mast cells.

Millions of people worldwide are exposed to arsenic (As), a toxicant which increases the risk of various cancers, cardiovascular disease and several other health problems. Arsenic is a potent endocrine disruptor, including of the estrogen receptor. It was recently shown that environmental estrogen-receptor disruptors can affect the signaling of mast cells, which are important players in parasite defense, asthma and allergy.

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening.

Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating.

Pompe disease was named after the Dutch pathologist Dr JC Pompe who reported about a deceased infant with idiopathic hypertrophy of the heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. The key pathologic finding was massive storage of glycogen in heart, skeletal muscle and many other tissues.

Assessment of altered conscious level in clinical practice.

This article will critically appraise the literature focusing on the use and application of the Glasgow Coma Scale (GCS). Historically the GCS tool was created in a 14-point format and later revised to a 15-point format. Critical analysis of this potentially confusing aspect will be explored.