Activity

Hyaluronan (HA) is abundant in the skin; while HA can be synthesized by the synthases (HAS1-3), HAS2 is the leading contributor. Dysregulation and accumulation of HA is implicated in the pathogenesis of diseases such as keloid scarring, lymphedema and metastatic melanoma. To understand how HA synthesis contributes to skin physiology, and pathologic and fibrotic disorders, we propose the development of skin-specific HA inhibition model, which tests an optimal delivery system of topical 4-methylumbelliferone (4-MU). A design-of-experiments (DOE) approach was employed to develop an optimal 4-MU skin-delivery formulation comprising propylene glycol, ethanol, and water, topically applied to dorsal skin in male and female C57BL/6J wildtype mice to determine the effect on HAS gene expression and HA inhibition. Serum and skin samples were analyzed for HA content along with analysis of expression of HAS1-3, hyaluronidases (HYAL 1-2), and KIAA1199. Using results from DOE and response surface methodology with genetic algorithm optimization, we developed an optimal topical 4-MU formulation to result in ∼70% reduction of HA in dorsal skin, with validation demonstrating ∼50% reduction in HA in dorsal skin. 4-MU topical application resulted in significant decrease in skin HAS2 expression in female mice only. Histology showed thicker dermis in male mice, whereas female mice had thinner dermal layer with more adiposity; and staining for HA-binding protein showed that topical 4-MU resulted in breakdown in HA. see more Our data suggest a topical 4-MU formulation-based dermal HA inhibition model that would enable elucidating the skin-specific effects of HA in normal and pathologic states.

Persistent activity limitations are common among road trauma survivors, yet access to rehabilitation in hospital and in the community remains variable. This study aimed to identify unmet rehabilitation needs following road trauma and assess the feasibility of a novel rehabilitation consultation service delivered

telehealth following hospitalization.

A pilot cohort study was conducted with survivors of road trauma who were hospitalized but did not receive formal inpatient rehabilitation. All participants received a multidisciplinary rehabilitation consultation

telehealth 1-3 weeks post-discharge, to assess rehabilitation needs and initiate treatment referrals as required. Functional and qualitative outcomes were assessed at baseline (1-7 days); one month and three months post-discharge.

38 participants were enrolled. All (100%) reported functional limitations at baseline; 86.5% were found to have unmet rehabilitation needs, and 75.7% were recommended rehabilitation interventions. Functional abilitymet rehabilitation needs following hospital discharge. Telehealth appears to be a feasible, convenient and acceptable mode of assessing these needs.Implications for rehabilitationSurvivors of road-related injuries often experience ongoing impairments and activity limitations.Among those who don’t receive rehabilitation in hospital, we found a high proportion (86.5%) had unmet rehabilitation needs after discharge.A telehealth rehabilitation service was feasible to deliver and could successfully identify unmet rehabilitation needs.The piloted telehealth intervention was viewed as acceptable, convenient and beneficial by patients.

We performed a retrospective study to assess the clinical utility of a new index, D-dimer/platelet count (DD/PLT) ratio, in discriminating preeclampsia from normal pregnancy and gestational hypertension during third trimester, compared to the biomarkers currently used, such as D-dimer (DD), platelet (PLT), lymphocyte (LIN) and neutrophil (NEU) counts, fibrinogen (FIB), PLT/NEU, NEU/LIN and PLT/LIN ratios.

We retrospectively included 213 subjects. Of them, 163 and 50 were singleton pregnant and healthy non-pregnant women, respectively. Among pregnant women, 105 had normal pregnancy, 33 had gestational hypertension, and 25 had preeclampsia.

Using Receiver Operating Curve (ROC) analysis, DD/PLT ratio showed significant higher area under the curve (AUC) (0.90; 95% confidence interval (CI) 0.84-0.95) in discriminating preeclampsia from normal pregnancy compared to those of DD, NEU, FIB, LIN, PLT/NEU, NEU/LIN and PLT/LIN ratios (

 < .03). In discriminating preeclampsia from gestational hypertension, the DD/PLT AUC (0.90; 95% CI 0.79-0.96) was significantly higher than those of DD, NEU, FIB, LIN, NEU/LIN and PLT/LIN ratios (

 < .03), and not statistically different from those of PLT (

 = .22) and PLT/NEU ratio (

 = .46).

This study shows that DD/PLT ratio helps to discriminate preeclampsia from normal pregnancy and gestational hypertension. Large-scale studies are needed to verify its clinical usefulness, and to suggest more appropriate cutoff values for a widespread use.

This study shows that DD/PLT ratio helps to discriminate preeclampsia from normal pregnancy and gestational hypertension. Large-scale studies are needed to verify its clinical usefulness, and to suggest more appropriate cutoff values for a widespread use.Nicotinamide riboside (NR), as a dietary supplement, can be converted to nicotinamide adenine dinucleotide (NAD+) in cells to support mitochondrial energy metabolism. However, the efficacy of oral administrated NR is limited due to its quick degradation in circulation and low bioavailability in targeted organs. In this study, we fabricated nanocrystal self-assembled microspheres by Nano Spray Dryer for oral delivery of NR. The structure of NR and resveratrol (RES) nanocrystal self-assembled microspheres (NR/RESms) is confirmed by the morphology, chemical structure, and crystallization. The NR/RESms displayed restricted NR release at the gastric acid-mimic condition (46% within 8 hours). Oral administration of NR/RESms for 8 hours significantly elevated NAD+ levels in serum (169.88 nM versus 30.93 nM in the NR group, p  less then  .01; and 66.89 nM in the NR + RES group, p  less then  .05), and enhanced NAD+ abundance in multiple organs in mice, exhibiting an improved oral NAD+ bioavailability. In addition, without any serious adverse effects on major organs, oral delivery of NR/RESms attenuated myocardial infarction (15.