Benchmarking of a multi-biomarker low-volume panel for Alzheimer's disease and related dementia research.

Introduction: In the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a technology that requires 15 µL of sample to measure more than 100 analytes.

European and African-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites.

Initially focused on the European population, multiple genome-wide association studies (GWAS) of complex diseases, such as type-2 diabetes (T2D), have now extended to other populations. However, to date, few ancestry-matched omics datasets have been generated or further integrated with the disease GWAS to nominate the key genes and/or molecular traits underlying the disease risk loci. In this study, we generated and integrated plasma proteomics and metabolomics with array-based genotype datasets of European (EUR) and African (AFR) ancestries to identify ancestry-specific muti-omics quantitative trait loci (QTLs).

Benchmarking of a multi-biomarker low-volume panel for Alzheimer's Disease and related dementia research.

Alzheimer's Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key.

A weight of evidence evaluation of the mode of action of isoeugenol.

Isoeugenol is one of several phenylpropenoid compounds that is used as a fragrance, food flavoring agent and in aquaculture as a fish anesthetic. Carcinogenicity testing in rats and mice by NTP resulted in clear evidence of carcinogenicity (hepatic adenomas/carcinomas) in male mice only. A nongenotoxic threshold mode of action (MOA) is postulated for isoeugenol and is discussed considering the IPCS MOA and Human Relevance Framework.

Developing a pragmatic consensus procedure supporting the ICH S1B(R1) weight of evidence carcinogenicity assessment.

The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes a comprehensive integrated Weight of Evidence (WoE) approach to determine the need for a 2-year rat carcinogenicity study. In the present work, experts from different organizations have joined efforts to standardize as much as possible a procedural framework for the integration of evidence associated with the different ICH S1B(R1) WoE criteria. The framework uses a pragmatic consensus procedure for carcinogenicity hazard assessment to facilitate transparent, consistent, and documented decision-making and it discusses best-practices both for the organization of studies and presentation of data in a format suitable for regulatory review.

Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry.

Timing of Jones Tube Placement After Excision of Nasal or Lacrimal Drainage System Malignancy: A Survey of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS).

Purpose: To elicit, from a survey of oculoplastic surgeons, the timing and reason for delaying Jones tube placement after the excision of nasal or lacrimal drainage system malignancy.

Methods: The authors reviewed current literature and distributed an anonymous survey to 627 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) to determine the length of time members wait to perform a Jones tube placement after the removal of nasal or lacrimal drainage system malignancy. The survey also included questions about the rationale for this waiting period.

Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123).

1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity.

Robert Warington and Heinrich Will: Friendship and Co-operation in Chemistry in Nineteenth Century Britain and Germany.

This paper discusses fourteen letters that Heinrich Will (1812-1890), Justus Liebig's (1803-1873) successor at the University of Giessen, sent to Robert Warington (1807-1867), the chemical operator at Apothecaries' Hall in London, between 1842 and 1854. The correspondence illuminates a range of topics related to the development of the British chemical community in mid-Victorian Britain - its organisations, networks, and commercial opportunities, as well as offering insights into the importance of family, friendship, and collegiality in sustaining scientific careers. Studying such an exchange of material and textual knowledge helps to further understand how science was organised and ideas disseminated in a key period for institutional development in chemistry.

A Grounded Theory Approach to Navigating Infertility Care During U.S. Military Service.

Introduction: In this study, we aimed to understand how active duty service members and their partners navigate the infertility care process within the Military Health System (MHS) while managing a military career.

Materials And Methods: We obtained Institutional Review Board approval to employ a qualitative design using grounded theory methods. We recruited participants using purposive sampling, followed by theoretical sampling.

Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats.

Background And Purpose: Analogues of fibroblast growth factor 21 (FGF21) demonstrate diverse metabolic benefits in preclinical models of type 2 diabetes, dyslipidaemia and non-alcoholic steatohepatitis (NASH), but clinical responses with different analogues are inconsistent. Efruxifermin is an Fc-FGF21 fusion protein with prolonged half-life and enhanced receptor affinity compared with native human FGF21. Efruxifermin is in clinical trials for the treatment of non-alcoholic steatohepatitis.

Unwise Relationships and an Unsound Valence Theory: The Chemical Career of Robert Fergus Hunter (1904-1963).

The life of the Imperial College-trained Robert Fergus Hunter (1904-1963) was a of a gifted chemist who appeared destined for a prominent academic career in organic chemistry. Two circumstances spoiled his chances. In the first place, he became associated with the declining fortunes of the weekly More seriously, as a professor at the Aligarh Muslim University in British India (1930-1936), he published papers on valence theory with the German-Jewish physicist Rudolf Samuel that fatally destroyed his chance of further academic preferment.

Current Trends of Practices in Nonclinical Toxicology: An Industry Survey.

The growth in drug development over the past years reflects significant advancements in basic sciences and a greater understanding of molecular pathways of disease. Benchmarking industry practices has been important to enable a critical reflection on the path to evolve pharmaceutical testing, and the outcome of past industry surveys has had some impact on best practices in testing. A survey was provided to members of SPS, ACT, and STP.

We're Stronger Together: A Collaboration to Support Military Families During the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has created challenges for every segment of the U.S. population, including military personnel and their families.

A different kind of Nierenstein reaction. The Chemical Society's mistreatment of Maximilian Nierenstein.

Between 1920 and 1922, the University of Bristol biochemist, Maximilian Nierenstein, published four papers in a series exploring the structure of catechin in the The Society then abruptly refused to accept any more of his papers on catechin, or any other subject. It provided him with no reasons for the embargo until 1925. It then transpired that Nierenstein was boycotted because it was deemed that he had not responded adequately to criticisms of his work made by his rival in catechin research, the German natural products chemist, Karl Freudenberg.

Age of diagnosis in familial Barrett's associated neoplasia.

The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC.

The Curious Story of the Chemical Society's Missing Obituary of John Lloyd Bullock.

The pharmaceutical and manufacturing chemist John Lloyd Bullock, who had joined the Chemical Society in 1842 and who played a fundamental role in the creation of the Royal College of Chemistry in 1845, did not receive an obituary when he died in 1905. Yet, nine years later on the eve of WW1, the Council of the Chemical Society suddenly commissioned an obituary from two German chemists. Although the curious circumstances of this omission and commission cannot be fully explained, their investigation provides an opportunity for an appraisal of Bullock's role in the history of chemistry and pharmacy.

The Economy, Climate Change and Infectious Diseases: Links and Policy Implications.

This short paper provides a modeling framework for unifying the economy, climate change and the outbreak of infectious diseases such as the recent COVID-19 pandemic. We stress that continuous growth of consumption activities, capital accumulation and climate change could increase the potential of the epidemic, its contact number or the probability of its arrival. This framework of analysis allows us to think of infectious disease policies in two stages.

Quantitative Systems Toxicology Modeling Predicts that Reduced Biliary Efflux Contributes to Tolvaptan Hepatotoxicity.

Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit enhanced susceptibility to tolvaptan hepatotoxicity relative to other patient populations. In a rodent model of ADPKD, the expression and function of the biliary efflux transporter Mrp2 was reduced, and biliary excretion of a major tolvaptan metabolite (DM-4103) was decreased. The current study investigated whether reduced biliary efflux could contribute to increased susceptibility to tolvaptan-associated hepatotoxicity using a quantitative systems toxicology (QST) model (DILIsym).

Finding the evidence: Screening of Military Family Research, 2014-2017.

Of 1.3 million active duty service members, the majority have family responsibilities; 54.3% are married, and 41.

The Healthcare Travelling Roadshow: a qualitative study of a rural community engagement initiative in Canada.

Introduction: Youth from rural communities face significant challenges in the pursuit of healthcare training. Healthcare trainees with a rural background are more likely than those without to practice rurally as healthcare professionals. The Healthcare Travelling Roadshow (HCTRS) is an initiative in Canada that provides rural youth with exposure to healthcare careers, while providing healthcare students with exposure to rural opportunities, and an interprofessional education experience.

Altered Expression and Function of Hepatic Transporters in a Rodent Model of Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common form of inherited polycystic kidney disease (PKD) and is a leading cause of kidney failure. Fluid-filled cysts develop in the kidneys of patients with ADPKD, and cysts often form in their liver and other organs. Previous data have shown that bile acids are increased in the liver of polycystic kidney (PCK) rats, a rodent model of PKD; these changes may be associated with alterations in liver transporter expression and function.