The case for neuregulin-1 as a clinical treatment for stroke.

Ischemic stroke is the leading cause of serious long-term disability and the 5th leading cause of death in the United States. Revascularization of the occluded cerebral artery, either by thrombolysis or endovascular thrombectomy, is the only effective, clinically-approved stroke therapy. Several potentially neuroprotective agents, including glutamate antagonists, anti-inflammatory compounds and free radical scavenging agents were shown to be effective neuroprotectants in preclinical animal models of brain ischemia.

Cultivating Relationships as a Community-Based Recruitment Strategy in Transdisciplinary Aging Research: Lessons From an Academic-Community Partnership.

Participation of Black American older adults in community-engaged research remains challenging in health sciences. The objectives of this study were to describe the specific efforts, successes, and challenges in recruiting Black American older adults in research led by the Health and Wellness in Aging Across the Lifespan core, part of the Virginia Commonwealth University Institute for Inclusion, Inquiry, and Innovation (iCubed). We conducted a cross-case analysis of 6 community-engaged research projects using the community-engaged research continuum model.

Socioeconomic Effects on Psychosocial Factors Among Low-Income Older Adults.

Objectives: Older adults have been disproportionately affected by COVID-19. The primary goal of this study is to determine the socioeconomic effects on psychosocial factors among low-income independent-living older adults, in an urban setting, during the COVID-pandemic.

Methods: Participants were recruited through Virginia Commonwealth University's Richmond Health and Wellness Program.

COVID in Context: The Lived Experience of Richmond's Low-Income Older Adults.

Taking a phenomenological approach, this qualitative study describes the lived experiences of low-income older adults during the COVID-19 pandemic. A socio-ecological model was used to organize the five identified themes describing the lived experience: socio-economic context, Black Lives Matter and the politics of race, COVID and polarized views of COVID, interpersonal context (social connections), and individual context (feelings, beliefs, and behaviors). Study findings illustrate the intersectionality of contextual influences on the experience of low-income older adults.

Bringing Transdisciplinary Aging Research From Theory to Practice.

There is a growing emphasis to use a transdisciplinary team approach to accelerate innovations in science to solve complex conditions associated with aging. However, the optimal organizational structure and process for how to accomplish transdisciplinary team science is unclear. In this forum, we illustrate our team's experience using transdisciplinary approaches to solve challenging and persistent problems for older adults living in urban communities.

Commentary: Physiological and Psychological Impact of Face Mask Usage during the COVID-19 Pandemic.

In this commentary, we discuss the physiological effects of wearing masks for prolonged periods of time, including special considerations, such as mask wearing among those who engage in exercise training, and concerns for individuals with pre-existing chronic diseases. In healthy populations, wearing a mask does not appear to cause any harmful physiological alterations, and the potentially life-saving benefits of wearing face masks seem to outweigh the documented discomforts (e.g.

Proximal Plantar Intrinsic Tendinopathy: Anatomical and Biomechanical Considerations in Plantar Heel Pain.

Plantar heel pain is often managed through podiatric and physical therapy interventions. Numerous differential diagnoses may be implicated in patients presenting with plantar heel pain; however, symptoms are often attributed to plantar fasciitis. Abductor hallucis, flexor digitorum brevis, and quadratus plantae share proximal anatomic attachment sites and mechanical function with the plantar fascia.

Neuroprotection by Exogenous and Endogenous Neuregulin-1 in Mouse Models of Focal Ischemic Stroke.

Identifying novel neuroprotectants that can halt or reverse the neurological effects of stroke is of interest to both clinicians and scientists. We and others previously showed the pre-clinical neuroprotective efficacy of neuregulin-1 (NRG-1) in rats following focal brain ischemia. In this study, we examined neuroprotection by exogenous and endogenous NRG-1 using a mouse model of ischemic stroke.

Regulation of inflammatory responses by neuregulin-1 in brain ischemia and microglial cells in vitro involves the NF-kappa B pathway.

Background: We previously demonstrated that neuregulin-1 (NRG-1) was neuroprotective in rats following ischemic stroke. Neuroprotection by NRG-1 was associated with the suppression of pro-inflammatory gene expression in brain tissues. Over-activation of brain microglia can induce pro-inflammatory gene expression by activation of transcriptional regulators following stroke.

Silver-Collagen Dressing and High-voltage, Pulsed-current Therapy for the Treatment of Chronic Full-thickness Wounds: A Case Series.

Research suggests high-voltage, pulsed-current electric therapy (HVPC) is safe and effective for treating chronic wounds, and some data suggest silver- and collagen-based dressings may facilitate healing. A combination therapy utilizing both HVPC and silver-collagen dressing may present clinical advantages. To explore the effect of the combined therapy for chronic full-thickness wounds, a prospective, consecutive case series study was conducted.

Bilateral gene interaction hierarchy analysis of the cell death gene response emphasizes the significance of cell cycle genes following unilateral traumatic brain injury.

Background: Delayed or secondary cell death that is caused by a cascade of cellular and molecular processes initiated by traumatic brain injury (TBI) may be reduced or prevented if an effective neuroprotective strategy is employed. Microarray and subsequent bioinformatic analyses were used to determine which genes, pathways and networks were significantly altered 24 h after unilateral TBI in the rat. Ipsilateral hemi-brain, the corresponding contralateral hemi-brain, and naïve (control) brain tissue were used for microarray analysis.

Return-to-Play Outcomes in Professional Baseball Players After Medial Ulnar Collateral Ligament Injuries: Comparison of Operative Versus Nonoperative Treatment Based on Magnetic Resonance Imaging Findings.

Background: The medial ulnar collateral ligament (UCL) is the primary static stabilizer to valgus stress of the elbow. Injuries to the UCL are common in baseball pitchers. In the 1970s, reconstructive surgery was developed.

Neuregulin-1 inhibits neuroinflammatory responses in a rat model of organophosphate-nerve agent-induced delayed neuronal injury.

Background: Neuregulin-1 (NRG-1) has been shown to act as a neuroprotectant in animal models of nerve agent intoxication and other acute brain injuries. We recently demonstrated that NRG-1 blocked delayed neuronal death in rats intoxicated with the organophosphate (OP) neurotoxin diisopropylflurophosphate (DFP). It has been proposed that inflammatory mediators are involved in the pathogenesis of OP neurotoxin-mediated brain damage.

Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response.

Background: Traumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24 h post-injury.

Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke.

Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology.

Acute neuronal injury and blood genomic profiles in a nonhuman primate model for ischemic stroke.

The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques.

Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury.

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague-Dawley rats were pretreated with pyridostigmine (0.

Spatiotemporal pattern of neuronal injury induced by DFP in rats: a model for delayed neuronal cell death following acute OP intoxication.

Organophosphate (OP) neurotoxins cause acute cholinergic toxicity and seizures resulting in delayed brain damage and persistent neurological symptoms. Testing novel strategies for protecting against delayed effects of acute OP intoxication has been hampered by the lack of appropriate animal models. In this study, we characterize the spatiotemporal pattern of cellular injury after acute intoxication with the OP diisopropylfluorophosphate (DFP).

Analysis of transcriptional profiles and functional clustering of global cerebellar gene expression in PCD3J mice.

The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and expression analysis systematic explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration.

Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia.

We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation.

Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia.

Neuregulin-1 (NRG-1) is a growth factor with potent neuroprotective capacity in ischemic stroke. We recently showed that NRG-1 reduced neuronal death following transient middle cerebral artery occlusion (tMCAO) by up to 90% with an extended therapeutic window. Here, we examined the neuroprotective potential of NRG-1 using a permanent MCAO ischemia (pMCAO) rat model.

Clinical outcomes following osteochondral autologous transplantation (OATS).

This study evaluated the clinical outcome in 21 patients (22 knees) undergoing osteochondral autologous transplantation (OATS) in the knee over a 5-year period. Sixteen knees in 15 patients were available for follow-up at an average of 40 months after the procedure. The clinical outcome was analyzed using the IKDC and Knee and Osteoarthritis Outcome Score (KOOS) evaluation forms, a subjective questionnaire, and a clinical examination.

Expression Analysis Systematic Explorer (EASE) analysis reveals differential gene expression in permanent and transient focal stroke rat models.

To gain greater insight on the molecular mechanisms that underlie ischemic stroke, we compared gene expression profiles in transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) stroke models using Expression Analysis Systematic Explorer (EASE) pathway analysis software. Many transcripts were induced in both stroke models, including genes associated with transcriptional pathways, cell death, stress responses and metabolism. However, EASE analysis of the regulated genes indicated molecular functions and biological processes unique to each model.

Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse.

Leptin-deficient (ob/ob) male mice are morbidly obese and exhibit impaired reproductive function. The objective of this study was to assess the effect of a leptin deficiency on testicular morphology, germ cell development, apoptotic activity within germ cells, and expression levels of apoptosis-related genes in the testis. Sixteen week-old ob/ob male mice (n = 8) and controls (n = 8) were killed, and their reproductive organs were weighed.

Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke.

We have previously shown that neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if administered before focal stroke. Here, we examined the therapeutic window and functional recovery after NRG-1 treatment in rats subjected to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Neuregulin-1 (2.