Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Distribution of the tensor of the vastus intermedius.

The tensor of the vastus intermedius (TVI) was first described by Grob et al. in 2016. It originates from the anteroinferior greater trochanter and inserts into the upper patella and receives blood and nerves independently of other muscles. It has been overlooked, but since micro-surgery and detailed rehabilitation treatments are being developed, more research on it is warranted. Here we report on the TVI in a Korean cadaveric study. A total of 58 cadavers (41 males and 17 females) were included. Thighs were examined using a standardized dissection protocol. The quadriceps femoris muscle was identified and its components were defined by blunt dissection. A total of 116 lower limbs were dissected. In 40 of them, there was a separately innervated TVI muscle belly between the fasciae of the vastus lateralis (VL) and the vastus intermedius (VI) muscles. TVIs were classed as independent (ID), VI, and VL types according to the relative relationship between the TVI, VL, and VI, and subdivided into two parts: Part 1 was the proximal muscular portion of the TVI attached to the VL or VI, and part 2 was the distal aponeurotic area. TVIs were analyzed in detail via 58 Korean cadavers. We subdivided them on the basis of their location and association with related muscles. A larger study is needed to clarify the function and prevalence of the TVI.

Comparison of core muscle strengthening exercise and stretching exercise in middle-aged women with fibromyalgia: A randomized, single-blind, controlled study.

BACKGROUND: Many studies have reported that exercise is effective for fibromyalgia and various types of exercise are recommended. However, most of exercises lack evidence for fibromyalgia symptoms. We aimed to examine the effect of core muscle strengthening exercise compared to general stretching exercise in fibromyalgia patients. METHODS: Forty fibromyalgia patients were enrolled. They were provided exercise program twice a week for 4 weeks: core muscle strengthening exercise and general stretching exercise.Outcome measures were Visual Analogue Scale, Borg Scale, fibromyalgia impact questionnaire (FIQ), widespread pain index, Symptom Severity Scale (SS), and balance scale and measured before and after exercise program. Balance function was assessed by checking the distance of sway on soft pad with eyes open (EO) and with eyes closed (EC). RESULTS: After program, FIQ, SS, EO, and eyes closed showed statistically significant differences in the strengthening group while Visual Analogue Scale, Borg scale, FIQ, widespread pain index, SS showed statistically significant differences in stretching group. And EO showed statistically significant differences in the intergroup analysis. CONCLUSIONS: Both exercise could improve symptoms of fibromyalgia but showed no significantly better efficiency with intergroup analysis. Only some balance function was improved with core muscle strengthening exercise with significant difference. Our study presents preliminary results regarding the comparison between both exercises for fibromyalgia through a randomized controlled trial.

Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures.

OBJECTIVE: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. METHODS: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. RESULTS: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. CONCLUSION: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

Nicotine stimulates CYP1A1 expression in human hepatocellular carcinoma cells via AP-1, NF-κB, and AhR.

Cytochrome P450 1A1 (CYP1A1) is a member of a subfamily of enzymes involved in the metabolism of both endogenous and exogenous substrates and the chemical activation of xenobiotics to carcinogenic derivatives. Here, the effects of nicotine, a major psychoactive compound present in cigarette smoke, on CYP1A1 expression and human hepatocellular carcinoma (HepG2) cell proliferation were investigated. Nicotine stimulated CYP1A1 expression via the transcription factors, activator protein 1, nuclear factor-kappa B, and the aryl hydrocarbon receptor (AhR) signaling pathway. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase, as well as RelA (or p65), mediated the upregulation of CYP1A1 of nicotine in HepG2 cells. The antioxidant compound, N-acetyl-cysteine, abrogated nicotine-activated production of reactive oxygen species and inhibited CYP1A1 expression by nicotine. Furthermore, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was inhibited by diphenyleneiodonium (an NADPH oxidase inhibitor). Thus, these results demonstrated that AhR played an important role in nicotine-induced CYP1A1 expression. Additionally, liver hepatocellular carcinoma HepG2 cells treated with nicotine exhibited markedly enhanced proliferation via CYP1A1 expression and Akt activation.

Clinical Practice Guideline for Cardiac Rehabilitation in Korea.

BACKGROUND: Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and 3 additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea. METHODS: This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of 33 authors-primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and 2 general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, 3 rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified. RESULTS: CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers cardiovascular mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR. CONCLUSION: Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates.

Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.

The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation. J. Cell. Biochem. 118: 2958-2967, 2017. © 2017 Wiley Periodicals, Inc.

Neurorestorative effects of epigallocatechin-3-Gallate on cognitive function in a chronic cerebral hypoperfusion rat model.

PURPOSE: This study investigated whether (-)-epigallocatechin-3-gallate (EGCG) can enhance cognition by a neurorestorative effect in a rat model of bilateral common carotid artery occlusion (BCCAO). METHODS: Forty-eight male, 8-week-old Sprague-Dawley rats were randomly allocated to four groups 6 weeks after BCCAO or sham operation: EGCG-single intravenous injection (25 mg/kg/day; SIV group), EGCG-multiple intraperitoneal injection (50 mg/kg/day for 5 days; MIP group), untreated BCCAO group (untreated group), and sham-operated group (sham group). RESULTS: Escape latency was significantly shorter in the SIV and MIP groups than in the untreated group. SIV and MIP groups were significantly different from the untreated group in the activity of superoxide dismutase and the content of malondialdehyde (p < 0.05). Protein expression level of brain-derived neurotrophic factor was not significantly different between groups (p > 0.05), while protein expression of vascular endothelial growth factor was significantly lower in the SIV group than in the untreated group (p < 0.05). Protein expression of N-methyl-D-aspartate receptor subunits NR1 and NR2B was significantly higher in the MIP group than in the untreated group (p < 0.05). CONCLUSIONS: EGCG administration at 6 weeks after BCCAO is neurorestorative via an anti-oxidant effect and synaptogenesis, except for angiogenesis.

Colorectal cancer in Crohn's colitis is comparable to sporadic colorectal cancer.

PURPOSE: It is now recognized that Crohn's disease (CD), similar to ulcerative colitis (UC), carries an up to 20-fold higher cancer risk, and the development of colorectal carcinoma (CRC) is a major long-term complication. Once CRC is present, molecular profiling is one of the components in selecting appropriate treatment strategies; however, in contrast to UC, genetic alterations in Crohn's colitis-associated CRC are poorly understood. METHODS: In a series of 227 patients with Crohn's colitis, we identified 33 cases of CRC (~14 %) and performed targeted mutational analysis of BRAF/KRAS/NRAS and determined microsatellite status as well as immunophenotype of the tumors. RESULTS: In the CRC cohort, the median age at time of cancer diagnosis was 58 (range 34-77 vs. 59.5 in sporadic; P = 0.81) and the median CD duration was 29 years (range 6-45). As a group, CRC complicating Crohn's colitis is BRAF (97 %) and NRAS (100 %) wild type and the vast majority is microsatellite stable (94 %); KRAS-mutations were found in six cases (18 %). Stage grouping, anatomic distribution, and overall survival were similar to sporadic CRC; however, long-standing CD (≥25 years) as well as gastric-immunophenotype (MUC5AC+) was associated with significantly shorter overall survival (P = 0.0029; P = 0.036, respectively). CONCLUSION: In summary, the clinicopathological and molecular profile of CD-associated CRC is similar to that observed in sporadic CRC.

Chrysin inhibits cell invasion by inhibition of Recepteur d'origine Nantais via suppressing early growth response-1 and NF-κB transcription factor activities in gastric cancer cells.

Cell invasion is one of crucial reasons for cancer metastasis and malignancy. Recepteur d'origine Nantais (RON) has been reported to play an important role in the cancer cell invasion process. High accumulation and activation of RON has been implicated in gastric adenocarcinoma AGS cells. Chrysin is a naturally occurring phytochemical, a type of flavonoid, which has been reported to suppress tumor metastasis. However, the effects of chrysin on RON expression in gastric cancer are not well studied. In the present study, we examined whether chrysin affects RON expression in gastric cancer, and if so, its underlying mechanism. We examined the effect of chrysin on RON expression and activity, via RT-PCR, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin significantly inhibited endogenous and inducible RON expression in a dose-dependent manner. After demonstrating that Egr-1 and NF-κB are the critically required transcription factors for RON expression, we discovered that chrysin suppressed Egr-1 and NF-κB transcription factor activities. Additionally, the phorbol-12-myristate-13-acetate- (PMA) induced cell invasion was partially abrogated by chrysin and an RON antibody. Our results suggest that chrysin has anticancer effects at least by suppressing RON expression through blocking Egr-1 and NF-κB in gastric cancer AGS cells.

Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model. STUDY DESIGN: Prospective, controlled animal study. METHODS: Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation. RESULTS: With respect to the functional outcome measurement, the functional outcomes improved after transection and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P < .05). On the electrophysiologic evaluation, there was significantly better performances in groups II, III, and IV when compared to group I with respect to the amplitude and excitation area of the compound motor action potentials (MAPs) 4 and 6 weeks after surgery (P < .05); group IV had the best performance. A Western blot assay showed that group II had marked expression of several neurotrophic factors. Groups II, III, and IV demonstrated better results in axon counts and myelin thickness when compared with group I. Based on quantitative histology analysis, group IV had the greatest myelinated axon fibers compared to the other groups (P < .05). CONCLUSIONS: The use of PRP and/or nMSCs promotes facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

Therapeutic experience on multiple contractures in sclerodermoid chronic graft versus host disease.

INTRODUCTION: A 25-year-old male underwent allogenic peripheral blood stem cell transplantation and developed sclerodermoid chronic graft versus host disease. He complained of limitation of motion of major joints and some difficulties with activities of daily living (ADL) performances. DISCUSSION: He had been treated with physical and occupational therapies. After the rehabilitative managements, range of motion and ADL performances improved slightly. CONCLUSION: Active and continuous multimodal rehabilitative treatment would be helpful in managing contracture and functional impairment and preventing the progression of the disease.