A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses.

Humanized mice are limited in terms of modeling human immunity, particularly with regards to antibody responses. Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated Kit mutant immunodeficient pups with human cord blood CD34 cells, followed by 17β-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyer's patches, and human thymic epithelial cells.

Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells.

Maturation of antibody responses entails somatic hypermutation (SHM), class-switch DNA recombination (CSR), plasma cell differentiation, and generation of memory B cells, and it is thought to require T cell help. We showed that B cell Toll-like receptor 4 (TLR4)-B cell receptor (BCR) (receptor for antigen) coengagement by 4-hydroxy-3-nitrophenyl acetyl (NP)-lipopolysaccharide (LPS) ( lipid A polysaccharide O-antigen) or TLR5-BCR coengagement by flagellin induces mature antibody responses to NP and flagellin in βδ and NSG/B mice. TLR-BCR coengagement required linkage of TLR and BCR ligands, "linked coengagement.

Trends in early postoperative major adverse cardiovascular and cerebrovascular events associated with bariatric surgery: an analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program data registry.

Background: The population undergoing bariatric surgery (BaS) has many cardiovascular risk factors that can lead to significant perioperative cardiovascular morbidity.

Objectives: We aimed to examine trends in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) after BaS.

Setting: Academic Hospital, United States METHODS: We performed a retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data registry for patients aged ≥18 years undergoing laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) from 2015 to 2019.

Impact of bariatric surgery on the risk of hospitalization due to influenza virus infection.

Background: Obesity independently increases the risk of hospitalization due to viral respiratory infections, including influenza virus and, more recently, severe acute respiratory syndrome coronavirus 2. As an independent risk factor, obesity impairs the immune response to viral infections and decreases the effectiveness of immunizations.

Objectives: Using influenza as a proxy, we aimed to determine the impact of bariatric surgery (BaS) on the risk of hospitalization due to viral respiratory infections.

LUBAC Suppresses IL-21-Induced Apoptosis in CD40-Activated Murine B Cells and Promotes Germinal Center B Cell Survival and the T-Dependent Antibody Response.

B cell activation by Tfh cells, i.e., through CD154 engagement of CD40 and IL-21, and survival within GCs are crucial for the T-dependent Ab response.

Improvement of glucose metabolism following rapid weight loss after bariatric surgery and its impact on reduction of visceral abdominal fat versus free fat muscle.

Background: Body fat distribution is highly associated with metabolic disturbances. Skeletal muscle plays an important role in glucose metabolism, as it serves as an important organ for glucose storage in the form of glycogen. In fact, low muscle mass has been associated with metabolic syndrome, type 2 diabetes (T2D), systemic inflammation, and decreased survival.

B Cell Endosomal RAB7 Promotes TRAF6 K63 Polyubiquitination and NF-κB Activation for Antibody Class-Switching.

Upon activation by CD40 or TLR signaling, B lymphocytes activate NF-κB to induce activation-induced cytidine deaminase and, therefore, Ig class switch DNA recombination, as central to the maturation of the Ab and autoantibody responses. In this study, we show that NF-κB activation is boosted by colocalization of engaged immune receptors, such as CD40, with RAB7 small GTPase on mature endosomes, in addition to signals emanating from the receptors localized on the plasma membrane, in mouse B cells. In mature endosomes, RAB7 directly interacts with TRAF6 E3 ubiquitin ligase, which catalyzes K63 polyubiquitination for NF-κB activation.

Lumbar Epidural Steroid Injections.

Lumbar epidural steroid injections under fluoroscopic guidance are used very commonly for the treatment of low back and lower extremity radicular pain. These procedures have been shown to be effective for pain relief in the short term and are relatively safe. The indications, evidence, and safety considerations for 2 different techniques-namely, interlaminar and transforaminal-are discussed.

Small Molecule Inhibition of Rab7 Impairs B Cell Class Switching and Plasma Cell Survival To Dampen the Autoantibody Response in Murine Lupus.

IgG autoantibodies mediate pathology in systemic lupus patients and lupus-prone mice. In this study, we showed that the class-switched IgG autoantibody response in MRL/Fas and C57/Sle1Sle2Sle2 mice was blocked by the CID 1067700 compound, which specifically targeted Ras-related in brain 7 (Rab7), an endosome-localized small GTPase that was upregulated in activated human and mouse lupus B cells, leading to prevention of disease development and extension of lifespan. These were associated with decreased IgG-expressing B cells and plasma cells, but unchanged numbers and functions of myeloid cells and T cells.

Core and Lumbopelvic Stabilization in Runners.

Core muscles provide stability that allows generation of force and motion in the lower extremities, as well as distributing impact forces and allowing controlled and efficient body movements. Imbalances or deficiencies in the core muscles can result in increased fatigue, decreased endurance, and injury in runners. Core strengthening should incorporate the intrinsic needs of the core for flexibility, strength, balance, and endurance, and the function of the core in relation to its role in extremity function and dysfunction.