Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

Background: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU).

Methods: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation.

Type 2 autoimmune pancreatitis associated with severe ulcerative colitis: Three case reports.

Background: Type two autoimmune pancreatitis is a rare and difficult to diagnose, steroid responsive non-IgG4 inflammatory pancreatopathy that can be associated with inflammatory bowel disease.

Case Summary: This case series describes three cases with varied clinical presentations and re-presentations of autoimmune pancreatitis, and all associated with an aggressive course of ulcerative colitis. The pancreatopathy was independent of bowel disease activity and developed in one case following colectomy.

Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants.

Background: The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment.

Methods: Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of first-degree association); 2) a clinical or genetic diagnosis of Hereditary Pancreatitis or Peutz-Jeghers syndrome irrespective of PDAC family history; or 3) a known PDAC predisposition germline pathogenic variant (BRCA2, PALB2, CDKN2A, or Lynch syndrome) with ≥one PDAC-affected first- or second-degree relative. Retrospective medical record review was conducted for APCSP participants enrolled at the participating Australian hospitals from January 2011 to December 2019.

A method for detection of SARS-CoV-2 RNA in healthy human stool: a validation study.

Background: Faecal shedding of SARS-CoV-2 has raised concerns about transmission through faecal microbiota transplantation procedures. Validation parameters of authorised tests for SARS-CoV-2 RNA detection in respiratory samples are described in product labelling, whereas the published methods for SARS-CoV-2 detection from faecal samples have not permitted a robust description of the assay parameters. We aimed to develop and validate a test specifically for detection of SARS-CoV-2 in human stool.

Diagnostic value of clinical examination for identifying patients with large- and small-fibre neuropathy.

Background: The diagnosis of polyneuropathy usually requires neurophysiological investigation, necessitating specialised testing and interpretation thereby increasing the time to final diagnosis.

Aims: To investigate the predictive value of the clinical examination in patients with potential neuropathies.

Methods: Patients were recruited based on their referral requesting neurophysiological testing.

The incidence of orthostatic intolerance after bariatric surgery.

Aims: Every year, over 200 000 individuals undergo bariatric surgery for the treatment of extreme obesity in the United States. Several retrospective studies describe the occurrence of orthostatic intolerance (OI) syndrome after bariatric surgery. However, the incidence of this syndrome remains unknown.

Safety and Accuracy of the Freehand Placement of C7 Pedicle Screws in Cervical and Cervicothoracic Constructs.

Background:  Cervical pedicle screws are advantageous in their biomechanical stability within cervical and cervicothoracic constructs. The seventh cervical vertebra contains relatively large pedicles and has a low incidence of vertebral artery localization within the transverse foramina. The freehand technique of pedicle screw insertion is advantageous in decreasing intraoperative radiation exposure both to the patient and surgeon.

Role of N-glycosylation in the expression of human SLC26A2 and A3 anion transport membrane glycoproteins .

The human solute carrier 26 (SLC26) gene family of anion transporters consists of 10 members (-, being a pseudogene) that encode membrane glycoproteins with 14 transmembrane segments and a C-terminal cytoplasmic sulfate transporter anti-sigma antagonist domain. Thus far, mutations in eight members of the family (-, , and ) have been linked to diseases in humans. Our goal is to characterize the role of N-glycosylation and the effect of mutations in SLC26A2 and A3 proteins on their functional expression in transfected HEK-293 cells.

Efficacy of selective laser trabeculoplasty following incisional glaucoma surgery.

Aim: To evaluate the efficacy of selective laser trabeculoplasty (SLT) in glaucomatous eyes with previous incisional glaucoma surgery.

Methods: A retrospective cohort of eyes that underwent SLT at a single institution from 2013-2015 were followed for 1y. Reduction in intraocular pressure (IOP) following SLT was evaluated in eyes with prior trabeculectomy with ExPress mini shunt (Alcon, Ft Worth, TX, USA), Ahmed valve (New World Medical, Cucamonga, CA, USA), or combined phacoemulsification-trabeculectomy.

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models.

SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis.

Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis.

Contributions of the Lectin and Polypeptide Binding Sites of Calreticulin to Its Chaperone Functions in Vitro and in Cells.

Calreticulin is a lectin chaperone of the endoplasmic reticulum that interacts with newly synthesized glycoproteins by binding to Glc1Man9GlcNAc2 oligosaccharides as well as to the polypeptide chain. In vitro, the latter interaction potently suppresses the aggregation of various non-glycosylated proteins. Although the lectin-oligosaccharide association is well understood, the polypeptide-based interaction is more controversial because the binding site on calreticulin has not been identified, and its significance in the biogenesis of glycoproteins in cells remains unknown.

Inhibition of the FKBP family of peptidyl prolyl isomerases induces abortive translocation and degradation of the cellular prion protein.

Prion diseases are fatal neurodegenerative disorders for which there is no effective treatment. Because the cellular prion protein (PrP(C)) is required for propagation of the infectious scrapie form of the protein, one therapeutic strategy is to reduce PrP(C) expression. Recently FK506, an inhibitor of the FKBP family of peptidyl prolyl isomerases, was shown to increase survival in animal models of prion disease, with proposed mechanisms including calcineurin inhibition, induction of autophagy, and reduced PrP(C) expression.

Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.

Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation.

The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis.

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis.

Depletion of cyclophilins B and C leads to dysregulation of endoplasmic reticulum redox homeostasis.

Protein folding within the endoplasmic reticulum is assisted by molecular chaperones and folding catalysts that include members of the protein-disulfide isomerase and peptidyl-prolyl isomerase families. In this report, we examined the contributions of the cyclophilin subset of peptidyl-prolyl isomerases to protein folding and identified cyclophilin C as an endoplasmic reticulum (ER) cyclophilin in addition to cyclophilin B. Using albumin and transferrin as models of cis-proline-containing proteins in human hepatoma cells, we found that combined knockdown of cyclophilins B and C delayed transferrin secretion but surprisingly resulted in more efficient oxidative folding and secretion of albumin.

Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase knockout mice.

Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AEC intrinsic apoptosis and that mitochondrial human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme, prevents oxidant-induced AEC apoptosis.

Denervation of the ear and the 'folding flower' illusion.

Following acute denervation of the ear, I experienced altered cutaneous sensory perception analogous to that reported by patients after limb amputation. This suggests that any sudden, complete loss of somaesthetic sensation can result in cortical reorganisation reflecting lost peripheral input. Although the short time course of the phenomenon suggests an initial functional reorganisation, it does not preclude longer time course structural alterations at multiple levels of the nervous system.

p53 mediates TNF-induced epithelial cell apoptosis in IBD.

Chronic ulcerative colitis (CUC) is characterized by increased intestinal epithelial cell (IEC) apoptosis associated with elevated tumor necrosis factor (TNF), inducible nitric oxide synthase (iNOS), and p53. We previously showed that p53 is increased in crypt IECs in human colitis and is needed for IEC apoptosis in chronic dextran sulfate sodium-colitis. Herein, we examined the roles of TNF and iNOS in regulating p53-induced IEC apoptosis in CUC.

Vitamin K epoxide reductase contributes to protein disulfide formation and redox homeostasis within the endoplasmic reticulum.

The transfer of oxidizing equivalents from the endoplasmic reticulum (ER) oxidoreductin (Ero1) oxidase to protein disulfide isomerase is an important pathway leading to disulfide formation in nascent proteins within the ER. However, Ero1-deficient mouse cells still support oxidative protein folding, which led to the discovery that peroxiredoxin IV (PRDX4) catalyzes a parallel oxidation pathway. To identify additional pathways, we used RNA interference in human hepatoma cells and evaluated the relative contributions to oxidative protein folding and ER redox homeostasis of Ero1, PRDX4, and the candidate oxidants quiescin-sulfhydryl oxidase 1 (QSOX1) and vitamin K epoxide reductase (VKOR).