Renal Phenotype Variations Among Families with Autosomal Alport Syndrome: Potential Role of Modifier Genes.

Background: Alport syndrome (AS) is an inherited disorder characterized by progressive renal disease, hearing deficits, and ocular abnormalities. This study investigates phenotypic variability among individuals with identical autosomal genetic mutations in COL4A3 and explores the potential influence of modifier genes. The study focuses on three families carrying the same COL4A3 mutation (c.

Interscalene and Erector Spinae Block Combination to Treat Latissimus Dorsi Repair: A Case Report.

Latissimus dorsi (LD) tendon rupture is a rare injury that occurs in athletes throughout a wide range of sports, including baseball, rock climbing, tennis, and golf. LD tendon repair requires analgesia in nerve distributions from C5-T6. A 33-year-old man presented for right LD tendon repair after rock climbing eight weeks prior to the operation.

Identification of Somatic Gene Signatures in Circulating Cell-Free DNA Associated with Disease Progression in Metastatic Prostate Cancer by a Novel Machine Learning Platform.

Purpose: Progression from metastatic castration-sensitive prostate cancer (mCSPC) to a castration-resistant (mCRPC) state heralds the lethal phenotype of prostate cancer. Identifying genomic alterations associated with mCRPC may help find new targets for drug development. In the majority of patients, obtaining a tumor biopsy is challenging because of the predominance of bone-only metastasis.

Intravenous Magnesium - Lidocaine - Ketorolac Cocktail for Postoperative Opioid Resistant Pain: A Case Series of Novel Rescue Therapy.

Background: Severe postoperative pain is principally managed by opioids. While effective, opioids do not provide adequate relief in many patients and cause many side effects, including antinociceptive tolerance and opioid-induced hyperalgesia. To evaluate if a combination of intravenous Magnesium, Lidocaine, Ketorolac (MLK cocktail) is a useful rescue therapy through synergistic pharmacological mechanisms for acute pain relief.

Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma.

Background: CD73-adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5'-nucleotidase (), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 ()) and A2 adenosine receptor (A2AR; ) transcript levels with markers of angiogenesis and antitumor immune response.

Food-specific antibodies in oesophageal secretions: association with trigger foods in eosinophilic oesophagitis.

Background: Food antigens are clearly implicated in the induction and persistence of eosinophilic oesophagitis. Dietary elimination to identify triggers is tedious and expensive. Alternatives that can mitigate cost and improve patient quality of life during this process are needed.

Comprehensive Analysis of AR Alterations in Circulating Tumor DNA from Patients with Advanced Prostate Cancer.

Background: Somatic alterations in circulating tumor DNA (ctDNA) may be associated with treatment response or prognosis in prostate cancer (PCa). The goal was to characterize androgen receptor gene (AR) amplifications and mutations detected in ctDNA from patients with PCa and to further understand the somatic genetic heterogeneity of advanced prostate cancer.

Patients And Methods: This study included a heterogeneous group of 892 patients with advanced PCa (predominantly castrate-resistant prostate cancer) with AR alterations detected in ctDNA that underwent next-generation sequencing of 54 to 73 genes via Guardant360 testing (Guardant Health, Inc.

Pulmonary Eosinophilic Granulomatosis with Polyangiitis Has IgG4 Plasma Cells and Immunoregulatory Features.

The immunologic mechanisms promoting eosinophilic granulomatosis with polyangiitis (EGPA) are unclear. To characterize the mechanisms underlying pulmonary EGPA, we examined and compared EGPA paraffin-embedded lung biopsies with normal lung biopsies, using immunostaining, RNA sequencing, and RT-PCR. The results revealed novel type 2 as well as immuneregulatory features.

De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes.

The genetic architecture of sporadic congenital heart disease (CHD) is characterized by enrichment in damaging de novo variants in chromatin-modifying genes. To test the hypothesis that gene pathways contributing to de novo forms of CHD are distinct from those for recessive forms, we analyze 2391 whole-exome trios from the Pediatric Cardiac Genomics Consortium. We deploy a permutation-based gene-burden analysis to identify damaging recessive and compound heterozygous genotypes and disease genes, controlling for confounding effects, such as background mutation rate and ancestry.

Chemogenetic Manipulations of Ventral Tegmental Area Dopamine Neurons Reveal Multifaceted Roles in Cocaine Abuse.

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of G signaling, but not G signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions.

CANOES: detecting rare copy number variants from whole exome sequencing data.

We present CANOES, an algorithm for the detection of rare copy number variants from exome sequencing data. CANOES models read counts using a negative binomial distribution and estimates variance of the read counts using a regression-based approach based on selected reference samples in a given dataset. We test CANOES on a family-based exome sequencing dataset, and show that its sensitivity and specificity is comparable to that of XHMM.

Hexahydro-β-acids potently inhibit 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice.

We previously reported that hexahydro-beta-acids (HBAs), reduced derivatives of beta-acids (BA) from hop (Humulus lupulus L.), displayed more potent anti-inflammatory activity than BA in lipopolysaccharide-stimulated murine macrophages. In this study, we investigated the effects and underlying molecular mechanisms of hexahydro-β-acids (HBAs) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mouse skin inflammation and in the two-stage carcinogenesis model.

Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

In human immune system, V(D)J recombination produces an enormously large repertoire of immunoglobulins (Ig) so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings.

The disintegrin contortrostatin in combination with docetaxel is a potent inhibitor of prostate cancer in vitro and in vivo.

Background: There are few available treatments for hormone refractory prostate cancer. Through the inhibition of integrins, contortrostatin (CN) effects tumor cell growth directly as well as through the inhibition of angiogenesis. The effect of CN in combination with docetaxel on prostate cancer cell lines in vitro and in vivo is evaluated in the present study.

A new method to evaluate polydisperse kaolinite clay particle removal in roughing filtration using colloid filtration theory.

Previous application of colloid filtration theory to roughing filtration has not considered a reliable method for determining a representative attachment factor for a polydisperse suspension (of constant particle density). Establishment of such a method would broaden the application of trajectory modelling in roughing filtration, and progress the development of a comprehensive database of attachment factors and surface charge potentials for various particle and fluid types. This study establishes a methodology for the application of colloid filtration theory to roughing filtration and incorporates recent advancements in theoretical single-collector efficiency.