Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDXMS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.

Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDXMS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.

no abstract available.

Whole-body vibration exercise (WBVe) can provide proper somatosensory stimulation and improve muscle strength in stroke patients. This study investigated the effects of WBVe on gait function and cortical activity in patients with chronic stroke. Thirty stroke patients were randomly assigned to either the WBVe or the control group. The WBVe group received the vibration in a half-squat position for 5 minutes at an intensity of 20 Hz. The control group kept the same posture but did not receive the vibration. Cortical activity was investigated using functional near-infrared spectroscopy (fNIRS). Gait function was assessed by a 10-m walk test (10MWT), a timed up and go (TUG) test, a Fugl-Meyer Assessment, and a Tinetti Performance-Oriented Mobility Assessment (TPOMA). In group analysis of the fNIRS data, oxygenated hemoglobin concentration was significantly increased in the ipsilesional supplementary motor area, bilateral sensorimotor cortex, and contralesional prefrontal cortex in the WBVe group compared to the control group (p < 0.05). Functional assessment demonstrated a significant interaction between time and group for the 10MWT and TUG test, suggesting that the WBVe group demonstrated meaningful improvement after intervention (p < 0.05). These results suggested that WBVe modulated the cerebral cortical activities and resulted in improvement of gait function in chronic stroke patients.

Whole-body vibration exercise (WBVe) can provide proper somatosensory stimulation and improve muscle strength in stroke patients. This study investigated the effects of WBVe on gait function and cortical activity in patients with chronic stroke. Thirty stroke patients were randomly assigned to either the WBVe or the control group. The WBVe group received the vibration in a half-squat position for 5 minutes at an intensity of 20 Hz. The control group kept the same posture but did not receive the vibration. Cortical activity was investigated using functional near-infrared spectroscopy (fNIRS). Gait function was assessed by a 10-m walk test (10MWT), a timed up and go (TUG) test, a Fugl-Meyer Assessment, and a Tinetti Performance-Oriented Mobility Assessment (TPOMA). In group analysis of the fNIRS data, oxygenated hemoglobin concentration was significantly increased in the ipsilesional supplementary motor area, bilateral sensorimotor cortex, and contralesional prefrontal cortex in the WBVe group compared to the control group (p < 0.05). Functional assessment demonstrated a significant interaction between time and group for the 10MWT and TUG test, suggesting that the WBVe group demonstrated meaningful improvement after intervention (p < 0.05). These results suggested that WBVe modulated the cerebral cortical activities and resulted in improvement of gait function in chronic stroke patients.

OBJECTIVES: Firefighters frequently experience traumatic events, high-tension situations and shift work. Therefore, the prevalence of insomnia of firefighters is higher than one of general population. Not only does the quality of sleep affect the satisfaction of personal life, but it also influences their performance for the public's safety. We investigated which factors affect the quality of sleep of firefighters. METHODS: After personally delivering 120 questionnaires to 3 fire stations, the survey was conducted when the consents were signed. It inquired about alcohol use, smoking, shift work, sleep quality, depression, anxiety, and experience of traumatic events. We then divided the firefighting officers in two groups according to the quality of sleep and compared the variables examined to conduct the logistic regression analyses according to the results. RESULTS: The poor sleeper group reported a higher level of current alcohol consumption, depression, anxiety and experience of traumatic events. Logistic regression analyses showed that the current alcohol intake (Crude odds ratio=3.707, 95% confidence interval=1.288–10.672, p=0.015 ; Adjusted odds ratio=3.288, 95% confidence interval=1.011–10.694, p=0.048) has a significant effect on sleep quality. CONCLUSIONS: Current alcohol consumption, depression, anxiety and experience of traumatic events were respectively associated with sleep quality of firefighters. When all significant factors considered, the current alcohol use was the only statistically significant. To improve the quality of sleep for firefighters, it will be necessary to evaluate alcohol intake, educate the poor sleep quality caused by alcohol, and provide specific interventions to reduce consumption.
Alcohol Drinking ; Anxiety ; Depression ; Firefighters ; Fires ; Humans ; Logistic Models ; Prevalence ; Sleep Initiation and Maintenance Disorders ; Smoke ; Smoking

Kidney matrix stones are a rare form of calculi, which are challenging to diagnose. Matrix stones consist of a proteinaceous material which has a radiolucent appearance that might be overlooked on imaging. Recently, endourological intervention has been the standard treatment method for matrix stones. We report a case of urinary matrix stones in a patient with type 1 diabetes mellitus and chronic kidney disease, in whom the stones formed into a pure matrix and were not visualized in the computed tomography scan. The stones were found after additional work-up, and they were managed using a transureteral stone basket, not through endourological intervention.

BACKGROUND: Mupirocin, a topical antimicrobial agent has been used for patients with methicillin-resistant Staphylococcus aureus and recently mupirocin resistance was issued in some studies. The objective of this study was to analyze prescription patterns of topical mupirocin, to evaluate appropriateness of prescriptions in the ambulatory setting, and to compare frequency of mupirocin usage in South Korea with that in United States. METHODS: Topical mupirocin prescription patterns (the number of prescription and a prescription period), and appropriateness of prescription (including a prescription rate over 10 days, a repeat prescription rate within 30 days and a prescription rate within labeled indications) were analyzed using the 2012 Health Insurance and Review and Assessment service-National Patient Sample dataset of South Korea. The National Ambulatory Medical Care Survey dataset was used to quantify topical mupirocin prescription in United States for comparison. RESULTS: In South Korea, the prescriptions rate for use over 10 days was 3%, the repeat prescription rate within 30 days was 8.87% and the prescription proportion within labeled indications was 33.84%. The most frequent diagnostic code was nonbacterial infection. The prescription rate per 1000 population of topical mupirocin in South Korea was calculated to be 46.07, whereas in United States was calculated to be 13.10. CONCLUSION: Topical mupirocin has been used frequently and inappropriately, so further studies are required to investigate the rationale behind such prescribing mupirocin patterns.
Ambulatory Care* ; Dataset ; Health Care Surveys ; Humans ; Insurance, Health ; Korea ; Methicillin-Resistant Staphylococcus aureus ; Mupirocin* ; National Health Programs* ; Prescriptions* ; United States

BACKGROUND: During laparoscopic surgery, high airway pressures are generally followed by a diaphragmatic shift and hyperventilation. We hypothesize that normocapnea can be maintained with the same amount of CO2 output (VCO2) during pneumoperitoneum (PP). METHODS: Six anesthetized rabbits were mechanically ventilated at a respiratory rate of 20/min with FIO2 0.5. At the end of the expiratory limb of the ventilator, the mean partial pressure of CO2 was measured. The internal carotid artery was catheterized. Baseline values for blood pressure, heart rate, arterial blood gas analysis, and ventilatory variables were obtained. CO2 gas was introduced into the peritoneum with an intra-abdominal pressure of 12 mmHg. The measurements at baseline and at PP1 were compared. The respiratory rate was changed from (20/min PP1, to 40/min PP2, 80/min PP3 or 120/min PP4) while calculating VCO2 and comparing ventilatory variables under PP at the same time. RESULTS: The peak inspiratory pressure (PIP) and tidal volume (VT) at PP1 increased, compared with baseline. With the same PaCO2, the VT decreased significantly from (45 +/- 8 ml PP1 to 29 +/- 5 ml PP2, 19 +/- 4 ml PP3 and 15 +/- 2 ml PP4), respectively. The PIP was reduced. However, the dead space to tidal volume ratio (VD/VT) was greater at higher RR during PP. CONCLUSIONS: PP increased the PIP and VT for the removal of overloaded CO2. Less VT at a higher respiratory rate could be used with the same amount of VCO2 during PP. However, the VD/VT was elevated by the induction of PP and by the increase in respiratory rate.
Blood Gas Analysis ; Blood Pressure ; Carbon ; Carotid Artery, Internal ; Catheters ; Extremities ; Heart Rate ; Hyperventilation ; Laparoscopy ; Partial Pressure ; Peritoneum ; Pneumoperitoneum ; Rabbits ; Respiratory Rate ; Tidal Volume ; Ventilators, Mechanical

Osteonecrosis of the femoral head is an idiopathic, debilitating and progressive disease. A number of traumatic or non-traumatic animal models have been reported for research on osteonecrosis. This study was performed to compare the efficacy of femoral head osteonecrosis in rabbits by traumatic and non-traumatic methods. Twenty-seven New Zealand White rabbits were divided into three experimental groups, nine heads each. Two groups were surgically induced into osteonecrosis; a steel cerclage wire was ligated tightly around the neck of the right femoral head (Group W), and the femoral neck was tied with a cerclage wire in the same way as in the W group, and burned by attachment of an electrode tip to the wire and then the wire was removed (Group B). The other group was induced into osteonecrosis with a single intra-muscular injection of 20 mg/kg methyl-prednisolone acetate single injection (Group M). In the control group, the left femoral head of animals in group W and B was used. After two weeks, rabbits were sacrificed and the femoral head and neck were collected. Osteonecrosis of the femoral head was evaluated by radiography, histology and immunohistology methods. Osteonecrosis lesions in the femoral head were identified in traumatic models of groups W and B. Cartilage degeneration in the superficial layer and TUNEL positive cells in the femoral head were detected more in Group B than in Group W. These findings revealed that short-term induced osteonecrosis of the femoral head was effectively achieved by cautery around the femoral neck.
Animals ; Burns ; Cartilage ; Cautery ; Electrodes ; Femur Neck ; Head ; In Situ Nick-End Labeling ; Models, Animal ; Neck ; Osteonecrosis ; Rabbits ; Steel