Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid review.

Background: Hearing loss affects approximately 1·6 billion individuals worldwide. Many cases are preventable. We aimed to estimate the annual number of new hearing loss cases that could be attributed to meningitis, otitis media, congenital rubella syndrome, cytomegalovirus, and ototoxic medications, specifically aminoglycosides, platinum-based chemotherapeutics, and antimalarials.

Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy improves lipid and glucose homeostasis in ob/ob mice.

Objective: The objective of this study was to compare the general and metabolic impact of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) with Roux-en-Y gastric bypass (RYGB) in an obese (ob/ob) mouse model.

Methods: 10-week-old male ob/ob mice underwent either SADI-S, RYGB, or laparotomy surgery (Sham group). General and metabolic parameters were assessed during a 5-week period thereafter.

Rare coding variants in CHRNB2 reduce the likelihood of smoking.

Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential to identify drug targets. We performed an exome-wide association study of smoking phenotypes in up to 749,459 individuals and discovered a protective association in CHRNB2, encoding the β2 subunit of the α4β2 nicotine acetylcholine receptor.

Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice.

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g.

The Impact of Hearing Loss and Its Treatment on Health-Related Quality of Life Utility: a Systematic Review with Meta-analysis.

Background: Hearing loss significantly impacts health-related quality of life (QoL), yet the effects of current treatments on QoL utility remain uncertain. Our objective was to describe the impact of untreated and treated hearing loss on QoL utility to inform hearing healthcare policy.

Methods: We searched databases for articles published through 02/01/2021.

Improved Outcomes in Severe Primary Graft Dysfunction After Heart Transplantation Following Donation After Circulatory Death Compared With Donation After Brain Death.

Background: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation.

Methods And Results: Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021.

ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma.

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk.

In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer.

The immune system can eliminate tumors, but checkpoints enable immune escape. Here, we identify immune evasion mechanisms using genome-scale in vivo CRISPR screens across cancer models treated with immune checkpoint blockade (ICB). We identify immune evasion genes and important immune inhibitory checkpoints conserved across cancers, including the non-classical major histocompatibility complex class I (MHC class I) molecule Qa-1/HLA-E.

The Future of heart procurement with donation after circulatory death: Current practice and opportunities for advancement.

Heart Donation after Circulatory Death (DCD) has the potential to significantly increase the number of patients benefitting from heart transplantation. However, the expansion of DCD heart transplantation is currently limited by unanswered questions pertaining to best practices in DCD heart procurement. Additionally, significant variability exists within regulatory frameworks, professional guidelines, and published practices of DCD procurement processes.

Validation of the Decision model of the Burden of Hearing loss Across the Lifespan (DeciBHAL) in Chile, India, and Nigeria.

Background: There is no published decision model for informing hearing health care resource allocation across the lifespan in low- and middle-income countries. We sought to validate the Decision model of the Burden of Hearing loss Across the Lifespan International (DeciBHAL-I) in Chile, India, and Nigeria.

Methods: DeciBHAL-I simulates bilateral sensorineural hearing loss (SNHL) and conductive hearing loss (CHL) acquisition, SNHL progression, and hearing loss treatment.

Population-scale analysis of common and rare genetic variation associated with hearing loss in adults.

To better understand the genetics of hearing loss, we performed a genome-wide association meta-analysis with 125,749 cases and 469,497 controls across five cohorts. We identified 53/c loci affecting hearing loss risk, including common coding variants in COL9A3 and TMPRSS3. Through exome sequencing of 108,415 cases and 329,581 controls, we observed rare coding associations with 11 Mendelian hearing loss genes, including additive effects in known hearing loss genes GJB2 (Gly12fs; odds ratio [OR] = 1.

A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope.

Introduction: Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs.

Left atrial strain is associated with adverse cardiovascular events in patients with end-stage renal disease: Findings from the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study.

Introduction: We lack cardiovascular (CV) markers for patients with end-stage renal disease (ESRD), and left atrial (LA) strain has not been studied definitively in this population. We examined associations of LA reservoir, conduit, and booster strain with major adverse cardiovascular events (MACE) among stable patients with ESRD on dialysis.

Methods: One hundred and ninety patients in the Cardiac, Endothelial and Arterial Stiffness in ESRD study underwent echocardiography, including strain imaging.

Zebrafish Is Necessary for Normal Development and Macrophage Migration.

Heme oxygenase function is highly conserved between vertebrates where it plays important roles in normal embryonic development and controls oxidative stress. Expression of the zebrafish heme oxygenase 1 genes is known to be responsive to oxidative stress suggesting a conserved physiological function. In this study, we generate a knockout allele of zebrafish and characterize the effects of and loss on embryonic development.

Perception of Health-Care Professionals on Presumed Consent in Formulation of Proper Organ Transplantation Regulatory System.

Background: Owing to the advancement in organ transplantation, treating an individual with organ failure in today's world has become possible. However, organ transplantation is lagging in the absence of adequate organ donations. Shortage of organs for transplantation is a challenge to developing countries like Nepal and developed countries like the USA and UK.

Hydrogen peroxide signaling via its transformation to a stereospecific alkyl hydroperoxide that escapes reductive inactivation.

During systemic inflammation, indoleamine 2,3-dioxygenase 1 (IDO1) becomes expressed in endothelial cells where it uses hydrogen peroxide (HO) to oxidize L-tryptophan to the tricyclic hydroperoxide, cis-WOOH, that then relaxes arteries via oxidation of protein kinase G 1α. Here we show that arterial glutathione peroxidases and peroxiredoxins that rapidly eliminate HO, have little impact on relaxation of IDO1-expressing arteries, and that purified IDO1 forms cis-WOOH in the presence of peroxiredoxin 2. cis-WOOH oxidizes protein thiols in a selective and stereospecific manner.

The role of mitochondrial reactive oxygen species in insulin resistance.

Insulin resistance is one of the earliest pathological features of a suite of diseases including type 2 diabetes collectively referred to as metabolic syndrome. There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Here we review the evidence linking mitochondrial reactive oxygen species generated within mitochondria with insulin resistance in adipose tissue and skeletal muscle, two major insulin sensitive tissues.

Genetic screening reveals phospholipid metabolism as a key regulator of the biosynthesis of the redox-active lipid coenzyme Q.

Mitochondrial energy production and function rely on optimal concentrations of the essential redox-active lipid, coenzyme Q (CoQ). CoQ deficiency results in mitochondrial dysfunction associated with increased mitochondrial oxidative stress and a range of pathologies. What drives CoQ deficiency in many of these pathologies is unknown, just as there currently is no effective therapeutic strategy to overcome CoQ deficiency in humans.

PCSK9 is not secreted from mature differentiated intestinal cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes lysosomal degradation of the LDL receptor and is a key regulator of cholesterol metabolism. After the liver, the small intestine is the second organ that highly expresses PCSK9. However, the small intestine's ability to secrete PCSK9 remains a matter of debate.

Preparation, validation and use of a vasoactive tryptophan-derived hydroperoxide and relevant control compounds.

The L-tryptophan-derived tricyclic hydroperoxide cis-WOOH was recently identified as a novel and biologically important factor for regulating vascular tone and blood pressure under inflammatory conditions and potentially other cellular redox signaling events. cis-WOOH is highly labile and currently not available commercially. In this protocol, we provide procedures for the synthesis, purification, quantification and characterization of cis-WOOH, its epimer trans-WOOH and their respective alcohols (cis-WOH and trans-WOH).