Promoting Bone Health through Weight-bearing, Resistance Training, and Balance Exercises

Osteoporosis and low bone density affect 54 million Americans. Advanced age, female gender, an underweight BMI, lack of estrogen, smoking, and sedentary lifestyle all increase one’s risk of developing osteoporosis or experiencing bone fractures from minor trauma. In addition, residents of northern states, like Vermont, experience an increased risk of bone loss over time due to limited exposure to sunlight and decreased physical activity over winter months. Although screening, calcium and vitamin D supplementation, general exercise, and treatment are largely discussed, patients are unaware of the specific exercise routines that can be done to strengthen their bones. In response, I created a handout outlining simple and safe weight-bearing, strength training, and balance exercises patients can perform to promote good bone health and prevent osteoporosis and fragility fractures.https://scholarworks.uvm.edu/fmclerk/1429/thumbnail.jp

Supporting Vermont Families in Packing Healthy Lunches for Children in Childcare

Introduction. Partnering with Hunger Free Vermont, an organization that works to end hunger and malnutrition across the state, we investigated the nutritional value of the packed meals parents provide for their children in early childcare. The USDA\u27s My Plate resource was used as a measure to assess variety, dividing foods into five groups: grains, dairy, vegetables, fruits, and protein. The results will help Hunger Free Vermont design nutrition education materials for childcare centers to provide to the families they serve. Methods. Online surveys were distributed, asking parents to report the foods they recently provided for their children in packed lunches, to rate how \u27healthy\u27 they thought those lunches were, and to note any barriers they experience to packing healthy foods. Results. Survey results showed that the average number of sweets packed by parents who had low confidence in their ability to pack healthy meals was significantly higher than the average number packed by parents with high confidence (p \u3c 0.05). Additionally, the total number of cited barriers was significantly higher in parents who had low confidence in their ability to pack healthy meals (p \u3c 0.01). Conclusions. Many parents cited time constraints and ‘picky’ children as barriers to providing healthy meals, with concerns about the expense of healthy items and lack of childcare for shopping or food-prep time following close behind. In the future, education materials that address children’s unhealthy food preferences or further investigations into barriers to providing healthy lunches may facilitate development of resources for Vermont families.https://scholarworks.uvm.edu/comphp_gallery/1259/thumbnail.jp

Epidemic Bhutanese Optic Atrophy

Beginning in the early 1990's, tens of thousands of ethnic Nepali Bhutanese were forced out of Bhutan as a result of the Bhutanese; government's policy of "one nation and one people." A majority of these persons resided, for up to twenty years, in camps along the; Eastern Nepal border with Bhutan before resettlement in third-party countries. Vitamin B12, among other micronutrient; deficiencies, was common in these camps. More than 100,000 individuals have been resettled, with over 80% coming to the United; States, with less than 3,000 Bhutanese refugee arriving in Vermont. A number of patients from the local Bhutanese refugee population were evaluated in the neuro-ophthalmology clinic at our academic medical center and found to have optic atrophy (OA) without identifiable cause. To better understand the scale and potential etiology of this problem, all cases of OA, from this group, referred to the neuro-ophthalmology clinic, were reviewed

3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths

Retinal ganglion cells (RGCs), the sole output cells of the retina, are a heterogeneous population of neurons that project axons to visual targets in the brain. Like most CNS neurons, RGCs are considered incapable of mounting long distance axon regeneration. Using immunolabeling-enabled 3D imaging of solvent-cleared organs (iDISCO) in transgenic mice, we tracked the entire paths of individual RGC axons and show that adult RGCs are highly capable of spontaneous long-distance regeneration, even without any treatment. Our results show that the Thy1-H-YFP mouse sparsely labels RGCs, consisting predominantly of regeneration-competent α-type RGCs (αRGCs). Following optic nerve crush, many of the YFP-labeled RGC axons extend considerable distances proximal to the injury site with only a few penetrating through the lesion. This tortuous axon growth proximal to the lesion site is even more striking with intravitreal ciliary neurotrophic factor (CNTF) treatment. We further demonstrate that despite traveling more than 5 mm (i.e., a distance equal to the length of mouse optic nerve), many of these circuitous axons are confined to the injury area and fail to reach the brain. Our results re-evaluate the view that RGCs are naturally incapable of re-extending long axons, and shift the focus from promoting axon elongation, to understanding factors that prevent direct growth of axons through the lesion and the injured nerve

Retinal microvascular and neuronal function in patients with multiple sclerosis: 2-year follow-up

•A prospective comprehensive study with a detailed assessment of retinal microstructure and neuronal functions in patients with RRMS.•The key findings were decreased axonal function measured as retinal nerve fiber layer birefringence in the temporal quadrant and vessel density in the deep vascular plexus at follow-up.•Subgroup analyses showed that the increased retinal blood flow volume occurred in patients with no evidence of disease activity, and with stable or improved visual function. Objective: To determine the longitudinal changes in retinal microstructure, microvasculature, microcirculation, and axonal and neuronal functions in patients with relapsing-remitting multiple sclerosis (RRMS) over the time course of about two years. Methods: A total of 30 patients (60 eyes) with RRMS were followed for a period of 27 ± 6 months and evaluated with a battery of clinical tests including low contrast letter acuity (LCLA), intraretinal layer thicknesses by optical coherence tomography (OCT), ganglion cell function by steady-state pattern electroretinography (PERG), axonal function by polarization-sensitive OCT, volumetric vessel density (VVD) by OCT angiography, and retinal tissue perfusion (RTP) by retinal function imager. Results: Axonal function measured as retinal nerve fiber layer birefringence in the temporal quadrant and vessel density in the deep vascular plexus were significantly decreased at 2-year follow-up (P 0.05). Conclusion: To our best knowledge, this is the first 2-year prospective comprehensive study with a detailed assessment of retinal microstructure and neuronal functions in patients with RRMS. The recovery of retinal microcirculation occurred in patients with NEDA, and stable or improved visual function, suggesting these measurements as potential imaging biomarkers for monitoring disease progression

Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature CNS neurons remain unclear. Here, we show that along with nuclear translocation, STAT3 translocates to mitochondria in mature CNS neurons upon cytokine stimulation. Loss- and gain-of-function studies using knockout mice and viral expression of various STAT3 mutants demonstrate that STAT3′s transcriptional function is indispensable for CNS axon regrowth, whereas mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth. STAT3′s localization, functions, and growth-promoting effects are regulated by mitogen-activated protein kinase kinase (MEK), an effect further enhanced by Pten deletion, leading to extensive axon regrowth in the mouse optic pathway and spinal cord. These results highlight CNS neuronal dependence on STAT3 transcriptional activity, with mitochondrial STAT3 providing ancillary roles, and illustrate a critical contribution for MEK in enhancing diverse STAT3 functions and axon regrowth

Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells

Neuronal subtypes show diverse injury responses, but the molecular underpinnings remain elusive. Using transgenic mice that allow reliable visualization of axonal fate, we demonstrate that intrinsically photosensitive retinal ganglion cells (ipRGCs) are both resilient to cell death and highly regenerative. Using RNA sequencing (RNA-seq), we show genes that are differentially expressed in ipRGCs and that associate with their survival and axon regeneration. Strikingly, thrombospondin-1 (Thbs1) ranked as the most differentially expressed gene, along with the well-documented injury-response genes Atf3 and Jun. THBS1 knockdown in RGCs eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both ipRGCs and non-ipRGCs, an effect that was dependent on syndecan-1, a known THBS1-binding protein. All structural domains of the THBS1 were not equally effective; the trimerization and C-terminal domains promoted regeneration, while the THBS type-1 repeats were dispensable. Our results identify cell-type-specific induction of Thbs1 as a novel gene conferring high regenerative capacity. •ipRGCs survive and regenerate axons well after injury•RNA-seq reveals unique sets of genes enriched in injured ipRGCs, including Thbs1 and Sdc1•Neural THBS1 promotes axon regeneration in various RGC types•Neural THBS1 promotes axon regeneration in a syndecan1-dependent manner Here, Bray et al. used a variety of transgenic mice to demonstrate high survival and regenerative ability of one neuronal type in the retina and show several factors within these neurons, including thrombospondin-1 and syndecan-1 that confer high regenerative capacity