The mutant mouse resource and research center (MMRRC) consortium: the US-based public mouse repository system.

Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease.

Incidence and Progression of Diabetic Retinopathy in American Indian and Alaska Native Individuals Served by the Indian Health Service, 2015-2019.

Importance: Estimates of diabetic retinopathy (DR) incidence and progression in American Indian and Alaska Native individuals are based on data from before 1992 and may not be informative for strategizing resources and practice patterns.

Objective: To examine incidence and progression of DR in American Indian and Alaska Native individuals.

Design, Setting, And Participants: This was a retrospective cohort study conducted from January 1, 2015, to December 31, 2019, and included adults with diabetes and no evidence of DR or mild nonproliferative DR (NPDR) in 2015 who were reexamined at least 1 time during the 2016 to 2019 period.

Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes.

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes.

Identifying genetic determinants of inflammatory pain in mice using a large-scale gene-targeted screen.

Identifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping Consortium. A biased set of 110 single-gene knockout mouse strains was screened for 1 or more nociception and hypersensitivity assays, including chemical nociception (formalin) and mechanical and thermal nociception (von Frey filaments and Hargreaves tests, respectively), with or without an inflammatory agent (complete Freund's adjuvant).

Computational analyses of the vibrational spectra of fentanyl, carfentanil and remifentanil.

The infrared (IR) spectra of fentanyl, carfentanil and remifentanil, and protonated salts, are computed using quantum chemistry methods. New experimental FTIR spectra are also reported and compared to the calculations. The accuracy of two density functional theory methods, B3LYP and M06-2X, are tested against higher level theories (MP2) and the experimental data.

Analysis by region of outcomes for patients with advanced renal cell carcinoma treated with cabozantinib or everolimus: a sub-analysis of the METEOR study.

Introduction: METEOR was a phase 3 trial (NCT01865747) of cabozantinib versus everolimus in adults with advanced or metastatic clear cell RCC previously treated with VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs). This analysis of METEOR compared outcomes for patients recruited from European and non-European countries.

Material And Methods: Adults with advanced/metastatic clear cell RCC who had received ≥ 1 prior VEGFR-TKI treatment were randomized 1:1 to receive cabozantinib or everolimus.

Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service's National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI).

Purpose: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services' (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI).

Methods: This was a retrospective analysis of 2016-2019 clinical data (n = 53,900).

Methotrexate Hepatotoxicity Monitoring Guidelines in Psoriasis and Rheumatoid Arthritis: Is There a Consensus?

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists.

Spatial Visualization of Human Anatomy through Art Using Technical Drawing Exercises.

Spatial visualization, the ability to mentally rotate three-dimensional (3D) images, plays a significant role in anatomy education. This study examines the impact of technical drawing exercises on the improvement of spatial visualization and anatomy education in a Neuroscience course. First-year medical students (n = 84) were randomly allocated into a control group (n = 41) or art-training group (n = 43).

Low Abundance of Three Tick Species in the Piedmont of North Carolina.

Multiple species of ticks, including Ixodes scapularis (Say, Ixodida:Ixodidae), Amblyomma americanum (L., Ixodida:Ixodidae), and Dermacentor variabilis (Say, Ixodida:Ixodidae), occur in high and increasing abundance in both the northeast and southeast United States. North Carolina is at the nexus of spread of these species, with high occurrence and abundance of I.

Exposure-response modeling of cabozantinib in patients with renal cell carcinoma: Implications for patient care.

Cabozantinib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of patients with advanced renal cell carcinoma (RCC) at a dose of 60 mg/day. As with other TKIs, cabozantinib is associated with high interpatient variability in drug clearance and exposure that can significantly impact safety and tolerability across a patient population. To optimize cabozantinib exposure (maintaining efficacy and tolerability) for the individual, patients may require treatment interruption with dose reduction (40 mg/day and then 20 mg/day).

Analytic Route to Tunneling Splittings Using Semiclassical Perturbation Theory.

We present an efficient, analytical, and simple route to approximating tunneling splittings in multidimensional chemical systems, directly from computations. The method is based on the Wentzel-Kramers-Brillouin (WKB) approximation combined with the vibrational perturbation theory. Anharmonicity and corner-cutting effects are implicitly accounted for without requiring a full potential energy surface.

Challenges of interpreting the musculoskeletal manifestation of lymphoma: A case report.

Background: Primary Bone Lymphoma can be challenging to interpret even for the experienced reviewer. This case demonstrates the subtle multimodality appearances encountered.

Case Summary: a gentleman in his late 70s with one week history of groin pain underwent plain radiography and subsequent further imaging.

The Indian Health Service Primary Care-Based Teleophthalmology Program for Diabetic Eye Disease Surveillance and Management.

Historically, fewer than half of American Indians and Alaska Natives (AI/AN) with diabetes received the annual diabetic retinopathy (DR) examination that is considered the minimum standard of care; this rate is similar to that of the general United States (U.S.) population with diabetes.

Hydrogen tunnelling in the rearrangements of carbenes: the role of dynamical calculations.

Tunnelling controlled chemical reactions are those which preferably proceed through pathways with high but narrow potential energy barriers, via quantum tunnelling, resulting in a product that would be disfavoured classically. These reactions are very sensitive to barrier width, height and temperature and so dynamical theoretical methods are required to describe these processes. Recent experimental work on charge-tagged phenyl pyruvic acid derivatives has found, in contrast to similar systems, no evidence of tunnelling control.

Calculations on the unimolecular decomposition of the nerve agent VX.

It is very difficult to perform experiments on the physical parameters for the thermal decomposition of chemical nerve agents such as VX and computations, therefore, are useful. The reaction dynamics of the gas-phase pericyclic hydrogen transfer of the nerve agent VX is studied computationally. The geometries of the stationary structures are calculated at M06-2X/jul-cc-pVTZ level of theory.

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project.

New Developments in Semiclassical Transition-State Theory.

This Feature Article describes some recent developments and applications of the Semiclassical Transition-State Theory (SCTST) for treating quantum tunneling in chemical reactions. A reduced dimensional form of the SCTST is discussed and is shown to be particularly efficient, as the required number of electronic structure calculations is reduced to an absolute minimum. We also describe how an alternative formulation of SCTST developed by Hernandez and Miller [ Chem.

Medication reconciliation in the emergency department performed by pharmacists.

Patients are at risk of having their medication histories inaccurately documented while being admitted to an emergency department (ED). Allowing a pharmacist to access patient medication history is an effective way of reducing the number of errors. We sought to determine if having a pharmacist (as opposed to the admitting clinical team) verify patients' medication histories would result in fewer discrepancies in inpatient medication regimens.

Use of graded Semmes Weinstein monofilament testing for ascertaining peripheral neuropathy in people with and without diabetes.

Aims: To assess peripheral neuropathy (PN) using graded Semmes Weinstein monofilaments (SWMs) and determine factors associated with PN among adult volunteers with and without diabetes.

Methods: Adult volunteers were assessed for distal sensory PN using three graded SWMs. Four PN levels were defined: 0 (no PN; felt all three filaments), 1 (subclinical PN; insensate to 1-g filament), 2 (insensate to 10-g), or 3 (insensate to 75-g).