The Effect of Exercise on Intraocular Pressure and Glaucoma.

Prcis: A review of the literature found that certain types of exercise and physical activity result in transient reductions in intraocular pressure and may have a beneficial effect on glaucoma severity and progression.

Introduction: Glaucoma is the most common cause of irreversible vision loss worldwide. Raised intraocular pressure (IOP) is the most important risk factor for the disease.

Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire.

Introduction: The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation (OXPHOS) deficiency on human immunity, we studied children with primary mitochondrial disease (MtD).

Methods: scRNAseq analysis of peripheral blood mononuclear cells was performed on matched children with MtD (N = 4) and controls (N = 4).

Real-world outcomes of intravitreal bevacizumab treat-and-extend for cystoid macular oedema secondary to central retinal vein occlusion.

Introduction: The purpose of this study was to report the real-world treatment outcomes using a treat-and-extend intravitreal bevacizumab protocol in cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO).

Methods: We conducted a retrospective case series of consecutive adult patients with CMO secondary to CRVO who presented between 1st January 2019 and 31st December 2021. All included patients were treated with bevacizumab using a treat-and-extend protocol, were followed up for a minimum of 6 months and had a clinical examination including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) at every visit.

Pyruvate dehydrogenase complex integrates the metabolome and epigenome in CD8+ memory T cell differentiation in vitro.

Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A () subunit using a CD4-cre recombinase-based strategy. Herein, we show that genetic ablation of PDC activity in T cells () leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS.

Severe Lenalidomide-Associated Hyperbilirubinemia.

Immunomodulatory drugs (IMids), such as thalidomide and lenalidomide, are used to treat plasma cell neoplasms and B-cell malignancies. We present a case of severe direct hyperbilirubinemia in a patient taking lenalidomide-based therapy for plasmacytoma. Imaging was unrevealing, and liver biopsy showed only mild sinusoidal dilation.

COVID-19-Associated Liver Injury.

This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.

Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory T cell differentiation in vitro.

Background: Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node.

Methods: To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A () subunit using a CD4-cre recombinase-based strategy.

Bouveret Syndrome in a Cirrhotic Patient.

Here, we present a case of Bouveret syndrome, a rare etiology of gallstone impaction in the setting of chole-enteric fistula, in a cirrhotic patient. This syndrome is most often seen in elderly patients with multiple comorbidities and as such has high morbidity and mortality rates. Because of its prevalence in this patient population and its rarity, there are no established guidelines for the workup and management of this disease.

Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder.

Despite advances in identifying rare and common genetic variants conferring risk for ADHD, the lack of a transcriptomic understanding of cortico-striatal brain circuitry has stymied a molecular mechanistic understanding of this disorder. To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from 60 individuals with and without ADHD. Significant differential expression of genes was found in the anterior cingulate cortex and, to a lesser extent, the caudate.

A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish.

Using adult zebrafish inner ears as a model for sensorineural regeneration, we ablated the mechanosensory receptors and characterized the single-cell epigenome and transcriptome at consecutive time points during hair cell regeneration. We utilized deep learning on the regeneration-induced open chromatin sequences and identified cell-specific transcription factor (TF) motif patterns. Enhancer activity correlated with gene expression and identified potential gene regulatory networks.

Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.

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Highlights of the drug-induced liver injury literature for 2021.

Introduction: In 2021, over 3,000 articles on Drug-Induced Liver Injury (DILI) were published, nearly doubling the annual number compared to 2011. This review selected DILI articles from 2021 we felt held the greatest interest and clinical relevance.

Areas Covered: A literature search was conducted using PubMed between 1 March 2021 and 28 February 2022.

Derivation of a natural language processing algorithm to identify febrile infants.

Background: Diagnostic codes can retrospectively identify samples of febrile infants, but sensitivity is low, resulting in many febrile infants eluding detection. To ensure study samples are representative, an improved approach is needed.

Objective: To derive and internally validate a natural language processing algorithm to identify febrile infants and compare its performance to diagnostic codes.

When Recurring Infections Mask an Atypical Presentation of Inflammatory Bowel Disease (IBD): A Re-Visitation and Literature Review.

Pyoderma gangrenosum (PG) is an uncommon and severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). Head or scalp involvement in this condition is exceedingly rare. Approximately one-third of presentations can be precipitated by skin trauma or infection, a phenomenon known as pathergy.

Ophthalmia neonatorum in a tertiary referral children's hospital: A retrospective study.

Objectives: The purpose of this study was to examine the aetiology, investigation and management of ophthalmia neonatorum (ON) presenting to a tertiary referral children's hospital over 5 years.

Methods: The eye swab data of all neonates presenting to Children's Health Ireland at Temple Street (Dublin, Ireland) between 1st January 2013 and 3rd September 2018 was analysed. The medical records of all patients with positive eye swab results were retrospectively reviewed.

Single-cell transcriptomics from human pancreatic islets: sample preparation matters.

Single-cell RNA sequencing (scRNA-seq) of human primary tissues is a rapidly emerging tool for investigating human health and disease at the molecular level. However, optimal processing of solid tissues presents a number of technical and logistical challenges, especially for tissues that are only available at autopsy, which includes pancreatic islets, a tissue that is highly relevant to diabetes. To assess the possible effects of different sample preparation protocols on fresh islet samples, we performed a detailed comparison of scRNA-seq data generated with islets isolated from a human donor but processed according to four treatment strategies, including fixation and cryopreservation.

MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells.

Background: The MAPK/ERK signaling pathway is an essential regulator of numerous cell processes that are crucial for normal development as well as cancer progression. While much is known regarding MAPK/ERK signal conveyance from the cell membrane to the nucleus, the transcriptional and epigenetic mechanisms that govern gene expression downstream of MAPK signaling are not fully elucidated.

Results: This study employed an integrated epigenome analysis approach to interrogate the effects of MAPK/ERK pathway inhibition on the global transcriptome, the active chromatin landscape, and protein-DNA interactions in 501mel melanoma cells.

The diagnostic value of optical coherence tomography angiography in diabetic retinopathy: a systematic review.

Purpose: Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Accurate investigative tools are essential for the early diagnosis and monitoring of the disease. Optical coherence tomography angiography (OCTA) is a recently developed technology that enables visualisation of the retinal microvasculature.

Prostate cancer susceptibility gene is a modulator of androgen receptor signaling and epithelial to mesenchymal transition.

In 2018, approximately 165,000 new prostate cancer (PC) cases will be diagnosed, and over 29,000 men will succumb to PC in the U.S. alone.

Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.

Background: It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain.

TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF.

Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi.

Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.

It is unclear how standing genetic variation affects the prognosis of prostate cancer patients. To provide one controlled answer to this problem, we crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease phenotype and SNP variation data in 493 F1 males identified a metastasis modifier locus on Chromosome 8 (LOD = 8.

Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc.

Metastasis is the primary cause of death in breast cancer. Earlier studies using a mammary tumorigenesis mouse model identified Necdin (Ndn)as a germline modifier of metastasis. Differential expression of Ndn induces a gene-expression signature that predicts prognosis in human breast cancer.