Impaired dopamine signaling in early diabetic retina: Insights from D1R and D4R agonist effects on whole retina responses.

The retina has low dopamine levels early in diabetes. To determine how low dopamine levels affected dopamine signaling, the effects of dopamine receptor agonists and mRNA localization were measured after 6 weeks of diabetes. Whole retina ex vivo electroretinogram (ERG) recordings were used to analyze how dopamine type 1 receptor (D1R) and type 4 (D4R) agonists change the light-evoked retinal responses of non-diabetic and 6-week diabetic (STZ injected) mouse retinas.

Identification, Elucidation and Deployment of a Cytoplasmic Male Sterility System for Hybrid Potato.

Recent advances in diploid F hybrid potato breeding rely on the production of inbred lines using the () gene. As a result of this method, female parent lines are self-fertile and require emasculation before hybrid seed production. The resulting F hybrids are self-fertile as well and produce many undesirable berries in the field.

Urinary Sphingosine-1-Phosphate as a Biomarker for Bladder Pain Syndrome.

Importance: Sphingosine-1-phosphate (S1P) is a signaling molecule involved in inflammation and bladder contraction.

Objectives: The aims of this case-control pilot study were to compare urinary S1P concentrations in bladder pain syndrome (BPS) participants to controls and determine whether these concentrations correlate with disease severity and duration.

Study Design: Adult females with BPS and controls were enrolled.

Quality of Pelvic Floor Therapy Videos on YouTube: Does Popularity Predict Reliability?

This study reviewed instructional videos on YouTube regarding pelvic floor physical therapy and assessed the association between the videos' popularity and the reliability of the videos' content. YouTube was searched using the terms relevant to pelvic floor muscle training. The first 100 videos for each search term were screened, and relevant metrics were collected for those meeting the inclusion criteria.

Midfoot width changes after first metatarsal osteotomy in hallux valgus surgery: A biomechanical effect?

Hallux valgus is a challenging pathology characterized by a valgus deformity in the metatarsophalangeal area of the first ray. The aim of this study was to analyze the influence of first metatarsal osteotomy on the relationship between midfoot bones in patients with hallux valgus. The sample consisted of patients from the orthopedics and traumatology outpatient clinic who underwent surgical treatment for hallux valgus.

Feasibility and safety of planned early discharge following laparotomy in gynecologic oncology with enhanced recovery protocol including opioid-sparing anesthesia.

Objective: This study aims to evaluate the feasibility and safety of planned postoperative day 1 discharge (PPOD1) among patients who undergo laparotomy (XL) in the department of gynecology oncology utilizing a modified enhanced recovery after surgery (ERAS) protocol including opioid-sparing anesthesia (OSA) and defined discharge criteria.

Methods: Patients undergoing XL and minimally invasive surgery (MIS) were enrolled in this prospective, observational cohort study after the departmental implementation of a modified ERAS protocol. The primary outcome was quality of life (QoL) using SF36, PROMIS GI, and ICIQ-FLUTS at baseline and 2- and 6-week postoperative visits.

Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation.

Parallel neurodegenerative phenotypes in sporadic Parkinson's disease fibroblasts and midbrain dopamine neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls.

A Predictive Autoantibody Signature in Multiple Sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster of PwMS that share an autoantibody signature against a common motif that has similarity with many human pathogens.

Visual Dysfunction in Diabetes.

Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina.

Effect of Ocrelizumab on B- and T-Cell Receptor Repertoire Diversity in Patients With Relapsing Multiple Sclerosis From the Randomized Phase III OPERA Trial.

Background And Objectives: The B cell-depleting anti-CD20 antibody ocrelizumab (OCR) effectively reduces MS disease activity and slows disability progression. Given the role of B cells as antigen-presenting cells, the primary goal of this study was to evaluate the effect of OCR on the T-cell receptor repertoire diversity.

Methods: To examine whether OCR substantially alters the molecular diversity of the T-cell receptor repertoire, deep immune repertoire sequencing (RepSeq) of CD4 and CD8 T-cell receptor β-chain variable regions was performed on longitudinal blood samples.

Parallel Neurodegenerative Phenotypes in Sporadic Parkinson's Disease Fibroblasts and Midbrain Dopamine Neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls.

Converting Hybrid Potato Breeding Science into Practice.

Research on diploid hybrid potato has made fast advances in recent years. In this review we give an overview of the most recent and relevant research outcomes. We define different components needed for a complete hybrid program: inbred line development, hybrid evaluation, cropping systems and variety registration.

Trends in Rural and Urban Cigarette Smoking Quit Ratios in the US From 2010 to 2020.

This cross-sectional study examines self-reported smoking patterns of adult participants in the US National Survey on Drug Use and Health (NSDUH).

Treatment of Metastatic Colorectal Carcinoma with Bevacizumab in First-Line and beyond First Progression: The KORALLE Non-Interventional Cohort Study.

Introduction: The non-interventional study (NIS) KORALLE evaluated the effectiveness and safety of bevacizumab in patients with metastatic colorectal carcinoma (mCRC) treated with bevacizumab in combination with fluoropyrimidine-based chemotherapy in the first-line setting and beyond first progression in routine clinical practice.

Methods: This prospective, multicenter NIS observed adult patients with mCRC who started first-line bevacizumab therapy. The planned maximum duration of observation per patient was 21 months.

Impaired Light Adaptation of ON-Sustained Ganglion Cells in Early Diabetes Is Attributable to Diminished Response to Dopamine D4 Receptor Activation.

Purpose: Retinal neuronal signaling is disrupted early in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is also growing evidence that retinal dopamine, a neuromodulator that mediates light adaptation, is reduced in early diabetes. Previously, we have shown that after 6 weeks of diabetes, light adaptation is impaired in ON-sustained (ON-s) ganglion cells in the mouse retina.

Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells.

The adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses covers only ∼3 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 and D2 families.

Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria.

Background: Chronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal.

Neofunctionalisation of the Sli gene leads to self-compatibility and facilitates precision breeding in potato.

Genetic gain in potato is hampered by the heterozygous tetraploid genome of cultivated potato. Converting potato into a diploid inbred-line based F1-hybrid crop provides a promising route towards increased genetic gain. The introduction of a dominant S-locus inhibitor (Sli) gene into diploid potato germplasm allows efficient generation of self-fertilized seeds and thus the development of potato inbred lines.

Vaginal Estrogen as First-Line Therapy for Recurrent Urinary Tract Infections in Postmenopausal Women and Risk Factors for Needing Additional Therapy.

Objectives: This retrospective cohort study aims to determine the proportion of postmenopausal women with recurrent urinary tract infections (rUTIs) who improve with vaginal estrogen cream alone and to identify risk factors for those who go on to require additional therapies.

Methods: Postmenopausal women presenting with rUTIs seen at a single institution over a 29-month period were identified. Patients who had not undergone previous treatment and were started on vaginal estrogen cream alone as first-line therapy were included in the study.

Cell type-specific transcriptomics identifies neddylation as a novel therapeutic target in multiple sclerosis.

Multiple sclerosis is an autoimmune disease of the CNS in which both genetic and environmental factors are involved. Genome-wide association studies revealed more than 200 risk loci, most of which harbour genes primarily expressed in immune cells. However, whether genetic differences are translated into cell-specific gene expression profiles and to what extent these are altered in patients with multiple sclerosis are still open questions in the field.

Application study of the EQ-5D-5L in oncology: linking self-reported quality of life of patients with advanced or metastatic colorectal cancer to clinical data from a German tumor registry.

Background: The EQ-5D-5L questionnaire is used in oncology to generate health-related quality of life (HRQoL) weights and corresponding health states. The purpose was to explore the relationship between demographic and clinical characteristics and HRQoL among advanced or metastatic colorectal cancer (CRC) patients by linking clinical data of a German CRC registry to self-reported HRQoL measures from the EQ-5D-5L.

Methods: The study sample included patients with advanced or metastatic CRC currently recruited in the German Tumor Registry Colorectal Cancer.

The effects of early diabetes on inner retinal neurons.

Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing.