Geographic variation in disease burden among patients with severe persistent asthma in the United States.

Background: In the United States, a few studies have evaluated geographic variation of severe asthma at the subnational level.

Objective: To assess state-level geographic variation in the prevalence and characteristics of severe persistent asthma in the United States.

Methods: Patients aged above or equal to 12 years with severe persistent asthma were identified using nationally representative data from IQVIA open-source Medical/Pharmacy Claims and PharMetrics Plus databases (January 2019-December 2020).

Therapeutic Potential of Extracts from (MTE) in Diabetic Nephropathy.

Diabetic nephropathy is a complication of diabetes that leads to end-stage kidney disease and is a major health burden worldwide. Prenylflavonoid compounds extracted from (MTE) exhibit anti-inflammation, anti-oxidant, and anti-bacterial properties. However, the effects of these compounds on diabetic nephropathy remain unclear.

Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases.

Introduction: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).

Methods: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding.

Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A systematic literature review and meta-analysis.

Introduction: High-grade pneumonitis is a severe and potentially life-threatening adverse event associated with concurrent chemoradiation (cCRT) in patients with non-small cell lung cancer (NSCLC). The aim of this study was to summarize and quantify the incidence of severe (grade 3-5) cCRT-induced pneumonitis in unresectable stage III NSCLC patients.

Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines.

Knockout of KLF10 Ameliorated Diabetic Renal Fibrosis via Downregulation of DKK-1.

Diabetes-induced chronic kidney disease leads to mortality and morbidity and thus poses a great health burden worldwide. Krüppel-like factor 10 (KLF10), a zinc finger-containing transcription factor, regulates numerous cellular functions, such as proliferation, differentiation, and apoptosis. In this study, we explored the effects of KLF10 on diabetes-induced renal disease by using a KLF10 knockout mice model.

Impact of Lurasidone and Other Antipsychotics on Body Weight: Real-World, Retrospective, Comparative Study of 15,323 Adults with Schizophrenia.

Purpose: The primary objectives were to describe weight changes following initiation of lurasidone versus other antipsychotics and estimate the risk of clinically relevant (≥7%) weight changes.

Patients And Methods: This retrospective, longitudinal comparative cohort study was based on electronic medical records (EMRs) of United States (US) adult patients with schizophrenia who were prescribed lurasidone or other antipsychotics as monotherapy between 1 April 2013 and 30 June 2019.

Results: Overall, the study included 15,323 patients with a diagnosis of schizophrenia; 6.

Mitochondrial DNA Variants in Patients with Liver Injury Due to Anti-Tuberculosis Drugs.

Background: Hepatotoxicity is the most severe adverse effect of anti-tuberculosis therapy. Isoniazid's metabolite hydrazine is a mitochondrial complex II inhibitor. We hypothesized that mitochondrial DNA variants are risk factors for drug-induced liver injury (DILI) due to isoniazid, rifampicin or pyrazinamide.

The Reduction in ED and Hospital Admissions in Medical Home Practices Is Specific to Primary Care-Sensitive Chronic Conditions.

Objective: To determine whether the Patient-Centered Medical Home (PCMH) transformation reduces hospital and ED utilization, and whether the effect is specific to chronic conditions targeted for management by the PCMH in our setting.

Data Sources And Study Setting: All patients aged 18 years and older in 2,218 primary care practices participating in a statewide PCMH incentive program sponsored by Blue Cross Blue Shield of Michigan (BCBSM) in 2009-2012.

Study Design: Quantitative observational study, jointly modeling PCMH-targeted versus other hospital admissions and ED visits on PCMH score, patient, and practice characteristics in a hierarchical multivariate model using the generalized gamma distribution.

Comparison of provider and plan-based targeting strategies for disease management.

Objectives: We aimed to describe and contrast the targeting methods and engagement outcomes for health plan-delivered disease management with those of a provider-delivered care management program.

Study Design: Health plan epidemiologists partnered with university health services researchers to conduct a quasi-experimental, mixed-methods study of a 2-year pilot. We used semi-structured interviews to assess the characteristics of program-targeting strategies, and calculated target and engagement rates from clinical encounter data.

Gender-Dimorphic Impact of PXR Genotype and Haplotype on Hepatotoxicity During Antituberculosis Treatment.

Women have a higher risk of drug-induced hepatotoxicity during antituberculosis treatment (HATT) than men. We hypothesized that single nucleotide polymorphism (SNP) genotype and derived haplotype of pregnane X receptor (PXR) gene, which could regulate the expression of phase I enzyme cytochrome P450 (CYP) 3A4, had a sex-specific influence on the risk of HATT. Six SNPs of the PXR gene were sequenced.

Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load.

Objectives: Hepatitis during anti-tuberculous treatment (HATT) has been an obstacle in managing patients with tuberculosis (TB). We evaluate the risk factors of HATT and the clinical implications of serum viral loads in those with concomitant hepatitis B or C viruses (HBV/HCV) infection.

Methods: We did a prospective study on patients with pulmonary tuberculosis in a medical center.

An active CD8alpha/pMHCI interaction is required for CD8 single positive thymocyte differentiation.

Recognition of viral antigenic peptides bound to major histocompatibility complex class I molecules (MHCI) by TCR is critical for initiating the responses of CD8(+) T cells that ultimately lead to elimination of virus-infected cells. This antigen recognition is enhanced by the CD8 coreceptor through its interaction with the peptide-MHCI complexes (pMHCI). Mouse CD8alphabeta can form two different complexes with pMHCI via either the CD8alpha- or CD8beta-dominated interaction.

CD8alphabeta has two distinct binding modes of interaction with peptide-major histocompatibility complex class I.

Interaction of CD8 (CD8alphaalpha or CD8alphabeta) with the peptide-major histocompatibility complex (MHC) class I (pMHCI) is critical for the development and function of cytolytic T cells. Although the crystal structure of CD8alphaalpha.pMHCI complex revealed that two symmetric CD8alpha subunits interact with pMHCI asymmetrically, with one subunit engaged in more extensive interaction than the other, the details of the interaction between the CD8alphabeta heterodimer and pMHCI remained unknown.

The TCR C beta FG loop regulates alpha beta T cell development.

The TCRbeta chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an alphabeta TCR cavity against which CD3epsilongamma may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15alphabeta TCR transfectants expressing a FG loop-deleted chain (betaDeltaFG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type beta-chain (betawt) upon TCR cross-linking.

Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer.

The crystal structure of a recombinant mouse single chain CD8alphabeta ectodomains at 2.4 A resolution reveals paired immunoglobulin variable region-like domains with a striking resemblance to CD8alphaalpha in size, shape, and surface electrostatic potential of complementarity-determining regions (CDR), despite <20% sequence identity between the CD8alpha and CD8beta subunits. Unlike the CD8alpha subunit(s) in the heterodimer or homodimer, the CDR1 loop of CD8beta tilts away from its corresponding CDR2 and CDR3 loops.

CD44 splicing pattern is associated with disease progression in pulmonary adenocarcinoma.

Background And Purpose: Certain alternatively spliced exons of CD44 gene have been associated with specific functions. However, these functions may have come from inclusion of a central array of alternatively spliced exons, rather than a single one. The goals of this study were to analyze all of the variant exons included by alternative splicing, the entire population of CD44 mRNA transcripts, and the prognostic implications of CD44 mRNA and protein isoforms expressed by non-small cell lung cancer (NSCLC).

Phage-displayed libraries of peptide/major histocompatibility complexes.

Characterizing peptide epitopes targeted by major histocompatibility complex (MHC)-restricted T cells of unknown specificity would have broad implications. In this article we introduce and validate an original phage-displayed library of noncovalent complexes of peptide and MHC (P/MHC). We show that soluble MHC molecules associate with peptides presented by a phage, thereby resulting in the formation of multivalent P/MHC phages.

Polygonum multiflorum extracts improve cognitive performance in senescence accelerated mice.

The objective of this study was to investigate the effects of Polygonum multflorum (PM) Thunb. on the learning and memory ability in one and seven-month-old male senescence accelerated mice (SAMP8). The mice were fed with two different diets for 18 weeks; they were casein dietary group (control group) and casein diet supplemented with PM extracts.

Stalk region of beta-chain enhances the coreceptor function of CD8.

CD8 glycoproteins are expressed as either alphaalpha homodimers or alphabeta heterodimers on the surface of T cells. CD8alphabeta is a more efficient coreceptor than the CD8alphaalpha for peptide Ag recognition by TCR. Each CD8 subunit is composed of four structural domains, namely, Ig-like domain, stalk region, transmembrane region, and cytoplasmic domain.

Involvement of the TCR Cbeta FG loop in thymic selection and T cell function.

The asymmetric disposition of T cell receptor (TCR) Cbeta and Calpha ectodomains creates a cavity with a side-wall formed by the rigid Cbeta FG loop. To investigate the significance of this conserved structure, we generated loop deletion (betaDeltaFG) and betawt transgenic (tg) mice using the TCR beta subunit of the N15 CTL. N15betawt and N15betaDeltaFG H-2(b) animals have comparable numbers of thymocytes in S phase and manifest developmental progression through the CD4(-)CD8(-) double-negative (DN) compartment.