Prevalence and risk factors of low vitamin D levels in children and adolescents with familial hypokalemic periodic paralysis.

Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively). CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted. WHAT IS KNOWN: • A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown. WHAT IS NEW: • Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.

Sex differences in the skin microbiome of burn scars.

Sex differences are observed in various spectrums of skin diseases, and there are differences in wound healing rate. Herein, sex differences were identified for the newly healed skin microbiome of burn patients. Fifty-two skin samples (26 normal skin, 26 burn scars) were collected from 26 burn patients (12 male, 14 female) and microbiota analysis was performed. The correlation between skin microbiota and biomechanical properties of burn scars was also investigated. There were no significant differences in clinical characteristics between male and female patients. Considering the biomechanical properties of burn scars and normal skin around it performed before sample collection, the mean erythema level of men's normal skin was significantly higher than that of women, whereas the mean levels of melanin, transepidermal water loss and skin hydration showed no significant sex differences. The erythrocyte sedimentation rate was significantly higher in females than that in males. Alpha diversity showed no significant differences between normal skin and burn scars in the male group. However, the scar was significantly higher than that of normal skin in the female group. Microbial network analysis revealed that the male group had more complex microbial network than the female group. Additionally, in the male group, the edge density and clustering coefficient were higher in burn scars when compared to normal skin, than the female group. There were sex differences in the results of microbiome of normal skin and burn scars. Some of the altered microbiota have been correlated with the biomechanical properties of burn scars. In conclusion, sex difference in the burn scar microbiome was confirmed. These results suggest that burn treatment strategies should vary with sex.

Effects of Factors Influencing Scar Formation on the Scar Microbiome in Patients with Burns.

Skin microbiome dysbiosis has deleterious effects, and the factors influencing burn scar formation, which affects the scar microbiome composition, are unknown. Therefore, we investigated the effects of various factors influencing scar formation on the scar microbiome composition in patients with burns. We collected samples from the burn scar center and margin of 40 patients with burns, subgrouped by factors influencing scar formation. Scar microbiome composition-influencing factors were analyzed using univariate and multivariate analyses. Skin graft, hospitalization period, intensive care unit (ICU) admission, burn degree, sex, age, total body surface area burned (TBSA), time post-injury, transepidermal water loss, the erythrocyte sedimentation rate, and C-reactive protein levels were identified as factors influencing burn scar microbiome composition. Only TBSA and ICU admission were associated with significant differences in alpha diversity. Alpha diversity significantly decreased with an increase in TBSA and was significantly lower in patients admitted to the ICU than in those not admitted to the ICU. Furthermore, we identified microorganisms associated with various explanatory variables. Our cross-sectional systems biology study confirmed that various variables influence the scar microbiome composition in patients with burns, each of which is associated with various microorganisms. Therefore, these factors should be considered during the application of skin microbiota for burn scar management.

Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin.

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell-cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 µg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts.

Post-burn hypertrophic scars are characterized by excessive accumulation of extracellular matrix secreted by fibroblasts. Exosomes are membrane lipid extracellular vesicles that play a pivotal role in cellular communication. Previous studies revealed the role of stem cell-derived exosomes in repairing damaged tissues, and also showed that cancer cell-derived exosomes could affect the disease pathogenesis. However, the functional properties of exosomes derived from hypertrophic scar fibroblasts (HTSFs) have not yet been studied extensively. In this study, we aimed to investigate whether HTSFs-derived exosomes can change the fibrosis-related signaling pathways in human normal fibroblasts (HNFs). HTSFs and HNFs were isolated from human hypertrophic scar tissues. HTSFs-derived exosomes were extracted and treated to HNFs. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect mRNA and protein expression, respectively, and cell proliferation and mobility were also assessed. Exosome treatment markedly increased cell proliferation and migration, and induced small mother against decapentaplegic (SMAD) signaling by increasing the levels of phosphorylated SMAD2 and SMAD1/5/8. The levels of TAK1 signaling components were also increased after exosome treatment to HNFs, including phosphorylated TAK1, p38, ERK, and JNK. HTSFs-derived exosomes further induced the epithelial-mesenchymal transition by decreasing the expression level of E-cadherin and increasing the expression levels of N-cadherin and vimentin. Consequently, the expression levels of fibronectin, type Ⅰ collagen, and type Ⅲ collagen were increased. Our results demonstrate the fibrotic property of HTSFs-derived exosomes, which suggests a potential functional role in hypertrophic scar development and a new therapeutic target.

Calpastatin-Mediated Inhibition of Calpain Ameliorates Skin Scar Formation after Burn Injury.

Hypertrophic scars, the most common complication of burn injuries, are characterized by excessive deposition of fibroblast-derived extracellular matrix proteins. Calpain, a calcium-dependent protease, is involved in the fibroblast proliferation and extracellular matrix production observed in certain fibrotic diseases. However, its role in the formation of post-burn hypertrophic skin scars remains largely unknown. Here, calpain expression and activity were assessed in skin fibroblasts obtained directly from patients with third-degree burns, who consequently developed post-burn hypertrophic scars. Furthermore, the antifibrotic effect of calpastatin, an endogenous calpain inhibitor, was evaluated in human fibroblasts and a murine burn model. The activity, mRNA levels, and protein levels of calpain were markedly higher in fibroblasts from the burn wounds of patients than in normal cells. Selective calpain inhibition by calpastatin markedly reduced not only the proliferation of burn-wound fibroblasts but also the mRNA and protein expression of calpain, transforming growth factor-beta 1, α-smooth muscle actin, type I and type III collagens, fibronectin, and vimentin in burn-wound fibroblasts. The anti-scarring effects of calpastatin were validated using a murine burn model by molecular, histological, and visual analyses. This study demonstrates the pathological role of calpain and the antifibrotic effect of calpastatin via calpain inhibition in post-burn hypertrophic scar formation.

CPEB1 or CPEB4 knockdown suppresses the TAK1 and Smad signalings in THP-1 macrophage-like cells and dermal fibroblasts.

Post-burn hypertrophic scar (HTS) is a form of excessive dermal fibrosis characterized by cutaneous scarring, which is common in patients following burn injury. Moreover, at least 50% of HTS are accompanied by inflammation. Cytoplasmic polyadenylation element binding (CPEB) proteins are key mRNA-binding proteins that control the translation of several mRNAs. However, their potential roles in treating dermal fibrosis and scarring remain unknown. Therefore, in this study, we aimed to investigate the effects of small interfering RNA (siRNA)-mediated knockdown of CPEB1 or CPEB4 in human THP-1 macrophages and dermal fibroblasts treated with LPS and TGF-ß1. We found significantly increased CPEB1 and CPEB4 mRNA and protein levels in LPS-treated THP-1 cells and TGF-ß1-treated fibroblasts. CPEB1 and CPEB4 knockdowns suppressed LPS-activated TAK1 signaling cascades by reducing the levels of TNF-α and phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65 in THP-1 cells. CPEB1 and CPEB4 knockdowns also attenuated TGF-ß1-activated Smad-dependent and -independent signaling cascades by reducing the levels of TAK1, p38, ERK, JNK, and phosphorylated Smad 2 and Smad 1/5/8 in fibroblasts. Furthermore, CPEB1 or CPEB4 knockdown markedly decreased the levels of fibrosis markers, including α-SMA, type I collagen, and fibronectin in fibroblasts. Our findings indicate that CPEB1 and CPEB4 are involved in the regulation of the TAK1 and Smad signalings in human macrophages and dermal fibroblasts. These activities may play a role in cutaneous scarring responses.

Effect of Combining Low Temperature Plasma, Negative Pressure Wound Therapy, and Bone Marrow Mesenchymal Stem Cells on an Acute Skin Wound Healing Mouse Model.

Low-temperature plasma (LTP; 3 min/day), negative pressure wound therapy (NPWT; 4 h/day), and bone marrow mesenchymal stem cells (MSCs; 1×106 cells/day) were used as mono- and combination therapy in an acute excisional skin wound-healing ICR mouse model. These therapies have been beneficial in treating wounds. We investigated the effectiveness of monotherapy with LTP, NPWT, and MSC and combination therapy with LTP + MSC, LTP + NPWT, NPWT + MSC, and LTP + NPWT + MSC on skin wounds in mice for seven consecutive days. Gene expression, protein expression, and epithelial thickness were analyzed using real time polymerase chain reaction (RT-qPCR), western blotting, and hematoxylin and eosin staining (H&E), respectively. Wound closure was also evaluated. Wound closure was significantly accelerated in monotherapy groups, whereas more accelerated in combination therapy groups. Tumor necrosis factor-α (TNF-α) expression was increased in the LTP monotherapy group but decreased in the NPWT, MSC, and combination therapy groups. Expressions of vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA), and type I collagen were increased in the combination therapy groups. Re-epithelialization was also considerably accelerated in combination therapy groups. Our findings suggest that combination therapy with LPT, NPWT, and MSC exert a synergistic effect on wound healing, representing a promising strategy for the treatment of acute wounds.

Extracorporeal Shock Wave Therapy Alters the Expression of Fibrosis-Related Molecules in Fibroblast Derived from Human Hypertrophic Scar.

Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0.03, 0.1, and 0.3 mJ/mm². At 24 h and 72 h after treatment, real-time PCR and western blotting were used to detect mRNA and protein expression, respectively, and cell viability and mobility were assessed. While HTSF viability was not affected, migration was decreased by ESWT. Transforming growth factor beta 1 (TGF-ß1) expression was reduced and alpha smooth muscle actin (α-SMA), collagen-I, fibronectin, and twist-1 were reduced significantly after ESWT. Expression of E-cadherin was increased, while that of N-cadherin was reduced. Expression of inhibitor of DNA binding 1 and 2 was increased. In conclusion, suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT, and has potential as a therapeutic target in the management of post-burn scars.

Low temperature plasma induces angiogenic growth factor via up-regulating hypoxia-inducible factor 1α in human dermal fibroblasts.

Numerous studies on the application of low temperature plasma (LTP) have produced impressive results, including antimicrobial, antitumor, and wound healing effects. Although LTP research has branched out to include medical applications, the detailed effects and working mechanisms of LTP on wound healing have not been fully investigated. Here, we investigated the potential effect of inducing growth factor after exposure to LTP and demonstrated the increased expression of angiogenic growth factor mediated by LTP-induced HIF1α expression in primary cultured human dermal fibroblasts. In cell viability assays, fibroblast viability was reduced 6 h and 24 h after LTP treatment for only 5 min, and pre-treating with NAC, a ROS scavenger, prevented cell loss. Fibroblast migration significantly increased at 6 h and 24 h in scratch wound healing assays, the expression of cytokines significantly changed, and regulatory growth factors were induced at 6 h and 24 h after exposure to LTP in RT-PCR or ELISAs. Specifically, LTP treatment significantly induced the expression of HIF1α, an upstream regulator of angiogenesis. Pre-treatment with the inhibitor CAY10585 abolished HIF1α expression and prevented LTP-induced angiogenic growth factor production according to immunoblotting, immunocytochemistry, and ELISA results. Taken together, our results provide information on the molecular mechanism by which LTP application may promote angiogenesis and will aid in developing methods to improve wound healing.

Investigation of cognitive circuits using steady-state cerebral blood volume and diffusion tensor imaging in patients with mild cognitive impairment following electrical injury.

PURPOSE: We utilized cerebral blood volume (CBV) magnetic resonance imaging and diffusion tensor imaging (DTI) to investigate changes in cognitive networks in patients experiencing cognitive dysfunction following electrical injury. METHODS: Cognitive function was assessed across various domains, including attention, verbal memory, executive function, and language. Depressive symptoms were also evaluated. CBV maps and DTI measures were obtained from 24 patients (age, 41.8 ± 5.8 years; education, 13.3 ± 1.9 years) and 24 healthy controls (age, 42.3 ± 2.7 years; education, 14.3 ± 1.9 years). CBV maps and DTI measures were compared between patients and controls, and correlations between these measures and each cognitive assessment score were examined. RESULTS: Patients exhibited lower attention, verbal memory, and executive function scores than controls (all p < 0.01). Patients also exhibited higher depression scores than controls (p < 0.01), as well as a predominant increase in CBV in the cerebellar vermis relative to that of controls (height p < uncorrected 0.001, extent p < corrected 0.05). Correlation analyses revealed a strong association between executive function scores and CBV in the bilateral posterior cingulate cortex and left mammillary body in patients (height p < uncorrected 0.001, extent p < corrected 0.05). There were no significant differences in DTI measures between patients and controls. CONCLUSION: The CBV maps showed hypermetabolism in the cerebello-limbic system; DTI did not find any microstructural changes. Our results suggest that patients experiencing cognitive dysfunction following electrical injury may possess a cognitive reserve that protects against deteriorating conditions such as dementia.

In Situ Pluripotency Factor Expression Promotes Functional Recovery From Cerebral Ischemia.

Recovery from ischemic tissue injury can be promoted by cell proliferation and neovascularization. Transient expression of four pluripotency factors (Pou5f1, Sox2, Myc, and Klf4) has been used to convert cell types but never been tested as a means to promote functional recovery from ischemic injury. Here we aimed to determine whether transient in situ pluripotency factor expression can improve neurobehavioral function. Cerebral ischemia was induced by transient bilateral common carotid artery occlusion, after which the four pluripotency factors were expressed through either doxycycline administration into the lateral ventricle in transgenic mice in which the four factors are expressed in a doxycycline-inducible manner. Histologic evaluation showed that this transient expression induced the proliferative generation of astrocytes and/or neural progenitors, but not neurons or glial scar, and increased neovascularization with upregulation of angiogenic factors. Furthermore, in vivo pluripotency factor expression caused neuroprotective effects such as increased numbers of mature neurons and levels of synaptic markers in the striatum. Dysplasia or tumor development was not observed. Importantly, neurobehavioral evaluations such as rotarod and ladder walking tests showed that the expression of the four factors dramatically promoted functional restoration from ischemic injury. These results provide a basis for novel therapeutic modality development for cerebral ischemia.

Preliminary Investigation of Pain-Related Changes in Cerebral Blood Volume in Patients With Phantom Limb Pain.

OBJECTIVE: To investigate changes in the pain network associated with phantom limb pain, magnetic resonance imaging (MRI) was used to measure cerebral blood volume (CBV) in patients who had undergone unilateral arm amputation after electrical injury. DESIGN: Case-controlled exploratory MRI study of CBV via MRI. SETTING: University hospital. PARTICIPANTS: Participants (N=26) comprised patients with phantom limb pain after unilateral arm amputation (n=10) and healthy, age-matched persons (n=16). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The intensity of phantom limb pain was measured using the visual analog scale (VAS). Depressive mood was assessed using the Hamilton Depression Rating Scale, and cognitive function was assessed using the Korean version of the Mini-Mental State Examination. Voxel-wise comparisons of relative CBV maps were made between amputees and controls over the entire brain volume. The relationship between individual participant CBV (measured in voxels) and VAS score was also examined. RESULTS: Compared with control participants, amputees exhibited greater degrees of depression; significantly higher CBV in the bilateral medial frontal area (orbitofrontal cortex [OFC] and pregenual anterior cingulate cortex [pACC]); and significantly lower CBV in the right midcingulate cortex, posterior cingulate cortex, and primary somatosensory cortex. CBV increased in the contralateral and ipsilateral hemispheres of the amputated arm, regardless of the amputation side. This CBV increase in the OFC and pACC was strongly correlated with pain intensity in all amputees. CONCLUSIONS: We observed increased CBV in regions associated with emotion in the cerebral pain network of patients who had undergone unilateral arm amputation after electrical injury. This study suggests that CBV changes were related to neuroplasticity associated with phantom limb pain.

Carbon Nanotube Yarn-Based Glucose Sensing Artificial Muscle.

Boronic acid (BA), known to be a reversible glucose-sensing material, is conjugated to a nanogel (NG) derived from hyaluronic acid biopolymer and used as a guest material for a carbon multiwalled nanotube (MWNT) yarn. By exploiting the swelling/deswelling of the NG that originates from the internal anionic charge changes resulting from BA binding to glucose, a NG MWNT yarn artificial muscle is obtained that provides reversible torsional actuation that can be used for glucose sensing. This actuator shows a short response time and high sensitivity (in the 5-100 × 10(-3) m range) for monitoring changes in glucose concentration in physiological buffer, without using any additional auxiliary substances or an electrical power source. It may be possible to apply the glucose-sensing MWNT yarn muscles as implantable glucose sensors that automatically release drugs when needed or as an artificial pancreas.

Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury.

Transplantation of mesenchymal stem cells (MSCs) has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE) in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS)-control (CON), PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

Comparative genome analysis of rice-pathogenic Burkholderia provides insight into capacity to adapt to different environments and hosts.

BACKGROUND: In addition to human and animal diseases, bacteria of the genus Burkholderia can cause plant diseases. The representative species of rice-pathogenic Burkholderia are Burkholderia glumae, B. gladioli, and B. plantarii, which primarily cause grain rot, sheath rot, and seedling blight, respectively, resulting in severe reductions in rice production. Though Burkholderia rice pathogens cause problems in rice-growing countries, comprehensive studies of these rice-pathogenic species aiming to control Burkholderia-mediated diseases are only in the early stages. RESULTS: We first sequenced the complete genome of B. plantarii ATCC 43733T. Second, we conducted comparative analysis of the newly sequenced B. plantarii ATCC 43733T genome with eleven complete or draft genomes of B. glumae and B. gladioli strains. Furthermore, we compared the genome of three rice Burkholderia pathogens with those of other Burkholderia species such as those found in environmental habitats and those known as animal/human pathogens. These B. glumae, B. gladioli, and B. plantarii strains have unique genes involved in toxoflavin or tropolone toxin production and the clustered regularly interspaced short palindromic repeats (CRISPR)-mediated bacterial immune system. Although the genome of B. plantarii ATCC 43733T has many common features with those of B. glumae and B. gladioli, this B. plantarii strain has several unique features, including quorum sensing and CRISPR/CRISPR-associated protein (Cas) systems. CONCLUSIONS: The complete genome sequence of B. plantarii ATCC 43733T and publicly available genomes of B. glumae BGR1 and B. gladioli BSR3 enabled comprehensive comparative genome analyses among three rice-pathogenic Burkholderia species responsible for tissue rotting and seedling blight. Our results suggest that B. glumae has evolved rapidly, or has undergone rapid genome rearrangements or deletions, in response to the hosts. It also, clarifies the unique features of rice pathogenic Burkholderia species relative to other animal and human Burkholderia species.

Multi-axis shoulder abduction splint in acute burn rehabilitation: a randomized controlled pilot trial.

OBJECTIVE: The traditional thermoplastic aeroplane splint for axillary burn contracture is heavy, uncomfortable, and time consuming and difficult to put on and off. The present study tested the effectiveness of a newly designed multi-axis shoulder abduction splint with an easy-to-change angle. DESIGN: Randomized controlled parallel assessor blinded pilot. SETTING: Inpatient rehabilitation center in a general hospital. SUBJECTS: Twenty-four patients with recent (< 30 days) burns around the shoulder joint were randomized into two groups. After two dropouts, 11 patients used the new splint for four weeks and 13 patient were left unsplinted for four weeks. INTERVENTIONS: The newly designed multi-axis shoulder abduction splint keeps the shoulder abducted at the highest possible angle. MAIN OUTCOMES: The range of motion of the shoulder joint was measured at 0, 1, 2, 3, and 4 weeks. Active abduction, flexion, and external rotation were measured according to the zero position method by placing the axis of the goniometer ventral to the shoulder joint. RESULTS: Repeated-measure ANOVA revealed that the splint group developed significantly better abduction (P = 0.020) and flexion (P = 0.036) over 4 weeks than the non-splint group. ANCOVA using the initial (0 week) angle and Shoulder Burn Depth Index as covariates revealed that the splint group had significantly better abduction than the non-splint group (P = 0.013). CONCLUSION: The new multi-axis shoulder abduction splint resulted in a significant improvement in shoulder abduction angle compared to unsplinted patients.

Therapeutic Potential of Resveratrol in Type I Gaucher Disease.

Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti-inflammatory, anti-oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis-inducing factor (AIF), Bax, cleaved caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol-treated patient cells were determined by thin-layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase-3 dose-dependently decreased, while those of ACAT1, E3BP, and CS dose-dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound.

Association between HTR7 genetic polymorphisms and alcohol dependence, using the alcohol use disorders identification test (AUDIT).

BACKGROUND: A recent genome-wide association study has identified 5-hydroxytrytamine (serotonin) receptor 7, adenylate cyclase-coupled (HTR7) as a risk gene for alcohol dependence. In addition, the serotonergic system has been considered as a modulator that plays an important role in alcohol use disorders. Functional, pharmacological, and genetic studies of serotonin neurotransmission have revealed that serotonin receptors are potential targets for the treatment of alcohol use disorders. The aim of this study is to investigate whether associations between HTR7 genetic polymorphisms and alcohol dependence could be replicated. METHODS: This study genotyped a total of 22 common single nucleotide polymorphisms (SNPs) in 459 alcoholic patients and 444 nonalcoholic controls. RESULTS: Logistic regression analysis of the case-control study, controlling for age and sex as covariates, showed nominal associations of 7 SNPs (p = 0.02 to 0.04; odds ratio = 0.60 to 1.35). In further linear regression analysis based on the Alcohol Use Disorders Identification Test score for alcohol dependence, 8 SNPs and 3 haplotypes showed relatively significant associations with alcohol dependence (minimum p = 0.001; p(corr) = 0.02). CONCLUSIONS: Although further replications and functional evaluations are needed, our findings suggest that genetic variations of HTR7 may contribute to the predisposition for alcohol dependence.

Copper-catalyzed oxidative C-O bond formation of 2-acyl phenols and 1,3-dicarbonyl compounds with ethers: direct access to phenol esters and enol esters.

A copper-catalyzed oxidative coupling of 2-carbonyl-substituted phenols and 1,3-dicarbonyl compounds with a wide range of dibenzyl or dialkyl ethers is described. This protocol provides an efficient preparation of phenol esters and enol esters in good yields with high chemoselectivity. This method represents an alternative protocol for classical esterification reactions.