[Gene therapy for visual function recovery].

Glaucoma is an age-related neurodegenerative disease and the leading cause of blindness, but currently no fundamental treatment has been present. The main treatment is to reduce intraocular pressure, which is expected to delay the progression of the disease. However, there are many glaucoma patients for whom progression cannot be controlled by lowering intraocular pressure alone, and the development of a fundamental treatment is required.

12 Tips for Including Disability Awareness within Undergraduate Medical Education Curricula.

Disability is extremely common, and there is a need for high quality medical school curricula on working with persons with disabilities. The goal of disability training is to provide the proper knowledge and skills to address the unique needs of PWD, mitigate health disparities, and help shape more compassionate and informed physicians. This article presents 12 tips to incorporate disability training into undergraduate medical education.

Membrane-anchored intracellular insulin receptor or insulin-like growth factor-1 receptor elicits ligand-independent downstream signaling.

Neurodegenerative diseases including glaucoma affect insulin signaling, and insulin treatment has been shown to reverse the neurodegenerative loss of dendritic complexity in retinal ganglion cells. Therefore, strategies for enhancing or maintaining insulin signaling are worth pursuing to establish new therapies for these diseases. In the present study, we generated constitutively active insulin receptor (F-iIR) and insulin-like growth factor-1 receptor (F-iIGF1R) using a system that forces membrane localization of the intracellular domains of these receptors by farnesylation.

Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury.

Purpose: To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.

Methods: Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.

A patient-centered approach to learning social determinants of health for first year medical students.

Introduction: To address health disparities, future physicians must understand the role of social determinants of health (SDH). Teaching SDH can be challenging. We created an authentic SDH curriculum using four real myocardial infarction (MI) patients.

Laparoscopic repair for internal hernia associated with colostomy: a case report.

A 63-year-old woman was admitted with abdominal pain two months after laparoscopic abdominoperineal resection for rectal cancer. Computed tomography revealed dilated small intestine had passed through a defect between the lifted sigmoid colon and abdominal wall. She was diagnosed with small bowel obstruction without strangulation due to internal hernia and managed nonoperatively based on her wish.

Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation.

Dedicator of cytokinesis 3 (DOCK3) is an atypical member of the guanine nucleotide exchange factors (GEFs) and plays important roles in neurite outgrowth. DOCK3 forms a complex with Engulfment and cell motility protein 1 (Elmo1) and effectively activates Rac1 and actin dynamics. In this study, we screened 462,169 low-molecular-weight compounds and identified the hit compounds that stimulate the interaction between DOCK3 and Elmo1, and neurite outgrowth in vitro.

Effects of constitutively active K-Ras on axon regeneration after optic nerve injury.

Visual disturbance after optic nerve injury is a serious problem. Attempts have been made to enhance the intrinsic ability of retinal ganglion cells (RGCs) to regenerate their axons, and the importance of PI3K/Akt and RAF/MEK/ERK signal activation has been suggested. Since these signals are shared with oncogenic signaling cascades, in this study, we focused on a constitutively active form of K-Ras, K-Ras, to determine if overexpression of this molecule could stimulate axon regeneration.

Perspective: Acknowledging a Hierarchy of Social Needs in Diabetes Clinical Care and Prevention.

The evidence of suboptimal social determinants of health (SDoH) on poor health outcomes has resulted in widespread calls for research to identify ways to measure and address social needs to improve health outcomes and reduce disparities. While assessing SDoH has become increasingly important in diabetes care and prevention research, little guidance has been offered on how to address suboptimal determinants in diabetes-related clinical care, prevention efforts, medical education and research. Not surprisingly, many patients experience multiple social needs - some that are more urgent (housing) than others (transportation/resources), therefore the order in which these needs are addressed needs to be considered in the context of diabetes care/outcomes.

Vision protection and robust axon regeneration in glaucoma models by membrane-associated Trk receptors.

Activation of neurotrophic factor signaling is a promising therapy for neurodegeneration. However, the transient nature of ligand-dependent activation limits its effectiveness. In this study, we solved this problem by inventing a system that forces membrane localization of the intracellular domain of tropomyosin receptor kinase B (iTrkB), which results in constitutive activation without ligands.

Peer observation of teaching: A feasible and effective method of physician faculty development.

Physician faculty learn teaching skills informally while fighting competing professional obligations. One underutilized proven technique to improve teaching skills is peer observation with feedback. We aimed to understand benefits and challenges of a physician faculty development program based on peer observation of teaching and to develop best practice recommendations for future program development.

ASK1 signaling regulates phase-specific glial interactions during neuroinflammation.

Neuroinflammation is well known to be associated with neurodegenerative diseases. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been implicated in neuroinflammation, but its precise cellular and molecular mechanisms remain unknown. In this study, we generated conditional knockout (CKO) mice that lack ASK1 in T cells, dendritic cells, microglia/macrophages, microglia, or astrocytes, to assess the roles of ASK1 during experimental autoimmune encephalomyelitis (EAE).

Effects of lighting environment on the degeneration of retinal ganglion cells in glutamate/aspartate transporter deficient mice, a mouse model of normal tension glaucoma.

Lighting conditions may affect the development of retinal degenerative diseases such as macular degeneration. In this study, to determine whether the lighting environment affects the progression of degeneration of retinal ganglion cells (RGCs), we examined glutamate/aspartate transporter (GLAST) heterozygous (GLAST) mice, a mouse model of normal tension glaucoma. GLAST mice were reared under a 12-h light-dark cycle (Light/Dark) or complete darkness (Dark/Dark) condition after birth.

Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation.

There is very little information on the transgenerational or genetic effects of low dose-rate ionizing radiation. We report the detection of the transgenerational effects of chronic low dose-rate irradiation in mice, at the molecular level in the whole genome, using array comparative genomic hybridization technology. We observed that the number of the mice with de novo copy number variations (specifically, deletions) was significantly increased in the offspring of C57BL/6J male mice exposed to 20 mGy/day gamma-rays for 400 days (total dose: 8000 mGy), as compared to non-irradiated controls.

Role of Adenosine Kinase in Sphingosine-1-Phosphate Receptor 1-Induced Mechano-Hypersensitivities.

Emerging evidence implicates the sphingosine-1-phosphate receptor subtype 1 (S1PR1) in the development of neuropathic pain. Continued investigation of the signaling pathways downstream of S1PR1 are needed to support development of S1PR1 antagonists. In rodents, intrathecal (i.

Enhanced pyrite passivation by carrier-microencapsulation using Fe-catechol and Ti-catechol complexes.

Acid mine drainage (AMD) formation is mainly caused by the oxidation of pyrite. Carrier-microencapsulation (CME) using metal-catecholate complexes has been proposed to passivate sulfide minerals by forming surface-protective coatings on their surfaces. Among the various metal-catecholate complexes, Ti-catecholate formed stable coatings having superior acid-resistance, but a thick enough passivating film required considerable time (ca.

Novel Non-Opioid Based Therapeutics for Chronic Neuropathic Pain.

Chronic neuropathic pain is currently a major health issue in U.S. complicated by the lack of non-opioid analgesic alternatives.

Cooking demonstrations to teach nutrition counseling and social determinants of health.

Background: Future physicians should feel comfortable educating patients on disease-specific diets, and culinary medicine is an innovative approach to preparing medical students for this task. We present an engaged-learning program where medical students give community cooking demonstrations to gain experience counseling adults on nutrition and simultaneously develop understanding of the social determinants of health. Student volunteers undergo training in culinary skills, nutrition, motivational interviewing, and social determinants of health.

Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury.

Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. In this study, we examined if topical ripasudil has therapeutic potential in adult mice after optic nerve crush (ONC). Topical ripasudil suppressed ONC-induced phosphorylation of p38 mitogen-activated protein kinase and ameliorated RGC death.

Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma.

Glaucoma is a neurodegenerative disease of the eye, which involves degeneration of retinal ganglion cells (RGCs): the output neurons of the retina to the brain, which with their axons comprise the optic nerve. Recent studies have shown the possible involvement of oxidative stress in the pathogenesis of glaucoma, especially in the subtype of normal tension glaucoma. Basic experiments utilizing rodent and primate models of glaucoma revealed that antioxidants protect RGCs under various pathological conditions including glutamate neurotoxicity and optic nerve injury.

Roles of the DOCK-D family proteins in a mouse model of neuroinflammation.

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown.

GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents.

Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response.