Effects of royal jelly on bone metabolism in postmenopausal women: a randomized, controlled study.

OBJECTIVES: This study aimed to evaluate the effects of royal jelly (RJ) supplementation on bone metabolism in postmenopausal women. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Seventy-two healthy postmenopausal women aged 45-60 years within 5 years after menopause were randomized into two groups: women in the RJ group (n = 36) received capsules containing dried RJ (equivalent to 3000 mg of fresh RJ); and women in the placebo group (n = 36) received placebo daily for 6 months. Bone mineral density (BMD) of the lumbar spine (L2-L4) and left proximal femur, hip structural analysis (HSA) of the left hip, and bone turnover markers were measured. RESULTS: Although women in the placebo group experienced a significant loss of BMD and deterioration in HSA parameters of the femur, no significant differences were found in these parameters in women in the RJ group. The levels of total procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase decreased significantly in the placebo group; however, the total P1NP level, a marker of bone formation, was not significantly different in the RJ group at postintervention compared with baseline. CONCLUSION: RJ consumption may ameliorate decreases in femoral BMD and strength in postmenopausal women.

Growth activation of influenza virus by trypsin and effect of T-705 (favipiravir) on trypsin-optimized growth condition.

Influenza virus is activated by proteolytic cleavage of hemagglutinin by trypsin. After determining the optimal trypsin concentration, intracellular and extracellular influenza A/PR/8/34 (H1N1) and A/Victoria/361/2011 (H3N2) virus productions were compared in cultures treated with T-705 (favipiravir) and GS 4071 (an active form of oseltamivir). Although both drugs efficiently inhibited extracellular viral RNA release in a dose-dependent manner, T-705 inhibited it to the level of the inoculum without trypsin treatment, while GS 4071 inhibited it to a final level 10 times higher than that without trypsin. T-705 inhibited intracellular viral RNA production to the level of input virus in both trypsin-treated and untreated cells. In contrast, GS 4071 dose-dependently inhibited intracellular viral RNA production in cells treated with trypsin but allowed viral RNA synthesis. The level of maximum inhibition by GS 4071was 10 times higher than that of cells without trypsin and 1,000 times greater than the inoculum titer in cells without trypsin. T-705 inhibited both intracellular and extracellular virus production 1,000 and 10 times more strongly, respectively, than GS 4071. T-705 has powerful anti-influenza activity in the absence of trypsin and even in the trypsin-optimized growth condition, suggesting the therapeutic advantage in treatment of influenza complicated with bacterial pneumonia. Keywords: influenza; T-705; Tamiflu; trypsin; bacterial trypsin-like protease.

Dose-saving isolation procedure in percutaneous ethanol sclerotherapy for venous malformations.

OBJECTIVES: To evaluate the feasibility and effectiveness of an isolation technique during ethanol injection sclerotherapy for venous malformations (VMs) in the head and neck region. METHODS: The subjects were 23 patients with 35 VM lesions in the head and neck, treated between 1999 and 2012. The mean lesion area was 3.75 ± 3.09 cm(2) (±standard deviation). We confirmed the contour of the lesions to be treated on a fully filled image on direct injection cisternography, and observed patterns of communicating drainage to systemic veins. The cisterns were evacuated by squeezing and were isolated by manual compression of the communicators. Ethanol (94.5%) with a contrast agent was then injected into both isolable and unisolable lesions, up to a total volume of 1 mL/cm(2), avoiding complications. We investigated the relationship between lesion size and injected ethanol dose, and also dose per unit area. RESULTS: Both manual evacuation by compression and isolation were performed in 20 (57.1%) isolable lesions, but not in 15 unisolable lesions. The mean injected ethanol dose was 0.65 ± 0.31 mL/cm(2) overall, 0.70 ± 0.32 in isolable and 0.59 ± 0.30 in unisolable lesions (NS). However, the injected ethanol dose was significantly lower for lesions sized >6 cm. Complete to near-complete shrinkage was observed in all isolable lesions, and in 60% of unisolable lesions (P < 0.05). Clinical outcome seemed unrelated to the injected ethanol dose or the dose per unit area. There was one case of recurrence and one complication in the unisolable lesions. No further relapses or complications were observed during the follow-up period of 38.6 ± 12.3 months. CONCLUSIONS: Clinical outcome was related to the isolability not to the injected dose. The isolation appears useful for improving the safety and effectiveness of ethanol sclerotherapy for VM.

A very low carbohydrate ketogenic diet prevents the progression of hepatic steatosis caused by hyperglycemia in a juvenile obese mouse model.

OBJECTIVE: To investigate whether the improvement in hyperglycemia by dietary control influences hyperglycemia-induced pathologies in tissues of juvenile obese (ob/ob) mice. DESIGN: Five-week-old ob/ob mice were fed a very low carbohydrate ketogenic diet (KD) for 7 weeks. The blood glucose levels and body weight were monitored during this period. Biochemical parameters in the serum and tissue pathologies of the mice were analyzed at the end of the 7-week period. RESULTS: The hyperglycemic phenotype of the ob/ob mice was improved by KD feeding for 7 weeks. Surprisingly, we found that KD feeding also drastically reduced the hepatic steatosis phenotype in ob/ob mice, while their obesity phenotype was unaltered. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that several proteins found in the liver of ob/ob mice fed a regular chow diet were undetectable after being fed KD. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) MASCOT search and western blot analysis revealed that the proteins absent from the mice fed KD included fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), which are key enzymes for lipogenesis in the liver. Fatty acid analysis supported the results because the ratio of C18:1, which is a major product of lipogenesis, was reduced by KD feeding. However, C18:2, which cannot be synthesized in mammalian cells but is present in the KD, was found to be a major component in the liver of KD-fed ob/ob mice. CONCLUSION: Hyperglycemia promotes hepatic steatosis via the lipogenic pathway in the liver of juvenile ob/ob mice. However, the development of steatosis is prevented by feeding KD owing to an improvement in hyperglycemia. We found that the progression of steatosis is reflected by the composition of fatty acids in the total lipids of the liver and serum.

A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.

Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.

Survival analysis of patients with high-grade gliomas based on data mining of imaging variables.

BACKGROUND AND PURPOSE: The prediction of prognosis in HGGs is poor in the majority of patients. Our aim was to test whether multivariate prediction models constructed by machine-learning methods provide a more accurate predictor of prognosis in HGGs than histopathologic classification. The prediction of survival was based on DTI and rCBV measurements as an adjunct to conventional imaging. MATERIALS AND METHODS: The relationship of survival to 55 variables, including clinical parameters (age, sex), categoric or continuous tumor descriptors (eg, tumor location, extent of resection, multifocality, edema), and imaging characteristics in ROIs, was analyzed in a multivariate fashion by using data-mining techniques. A variable selection method was applied to identify the overall most important variables. The analysis was performed on 74 HGGs (18 anaplastic gliomas WHO grades III/IV and 56 GBMs or gliosarcomas WHO grades IV/IV). RESULTS: Five variables were identified as the most significant, including the extent of resection, mass effect, volume of enhancing tumor, maximum B0 intensity, and mean trace intensity in the nonenhancing/edematous region. These variables were used to construct a prediction model based on a J48 classification tree. The average classification accuracy, assessed by cross-validation, was 85.1%. Kaplan-Meier survival curves showed that the constructed prediction model classified malignant gliomas in a manner that better correlates with clinical outcome than standard histopathology. CONCLUSIONS: Prediction models based on data-mining algorithms can provide a more accurate predictor of prognosis in malignant gliomas than histopathologic classification alone.

Two cases of single-stage lip and nostril reconstruction in holoprosencephaly.

Holoprosencephaly is a rare disorder of embryological development that presents with midline clefting of the lip. The incidence has been estimated at approximately 1 in 15,000. Previously, infants with severe holoprosencephaly were thought to die within 1-2 years of birth and seldom to benefit from surgery. Survival has increased with improved perinatal care and support services. Parents often request complete cheiloplasty, because the presence of a columella greatly influences aesthetic outcome. The authors report two cases of simultaneous columella reconstruction with cheiloplasty.

Working hours, occupational stress and depression among physicians.

BACKGROUND: Physicians report high prevalence of depression, work long hours and are exposed to many occupational stresses (OSs). AIMS: To investigate the cross-sectional association between working hours, OS and depression among physicians. METHODS: A self-administered questionnaire was mailed to 1902 alumni of a medical school. The questionnaire evaluated working hours in the previous week, OS assessed by the effort-reward imbalance model, social support and depression evaluated by the Center for Epidemiologic Studies Depression scale. The associations between these occupational factors and depression were analyzed using multiple logistic regression. RESULTS: The questionnaire was returned by 795 alumni (response rate, 42%), and 706 respondents (534 men and 172 women) were suitable for analysis. The odds ratio (OR) of depression in the long working hours group (>70 h/week) was 1.8 (95% CI: 1.1-2.8) compared with the short working hours group (<54 h/week), adjusted for basic attributes. The adjusted ORs of depression in the upper effort-reward ratio (ERR) tertile versus the lower ERR tertile were 0.6 (0.2-1.8) in the short working hours group, 8.5 (3.0-24.0) in the middle working hours group and 9.9 (3.8-25.7) in the long working hours group. The adjusted ORs of depression stratified according to working hours and ERR tended to be higher in the groups with a higher ERR, but no association between working hours and depression was found. CONCLUSIONS: This study indicates that the management of OS is needed as a countermeasure against depression among physicians.

Long beneficial effects after lipo-prostaglandin E1 administration on the ischemic gastric tube in pigs.

Lipo-prostaglandin E1 (PGE1) is a new preparation of PGE1 in which it is bound to lipids in order to slow PGE1 release and delay its rate of metabolism. We investigated how long the beneficial effects of intravenous administration of lipo-PGE1 on the ischemic gastric tube continue. The gastric tube was constructed using 15 domestic pigs under general anesthesia and saline, unmodified PGE1 and lipo-PGE1 were infused continuously at a rate of 0.05 microg/kg/min for 10 minutes. Tissue blood flow (TBF) was analyzed from before administration to 120 minutes after the end of administration. There were no obvious changes in TBF during the administration of saline. However, TBF during treatment with unmodified PGE1 and lipo-PGE1 was significantly increased to 13.1 +/- 1.3 and 13.5 +/- 1.4 mL/min/100 g, respectively (paired t-test; P < 0.01). Although TBF was significantly decreased to 8.0 +/- 1.0 mL/min/100 g on 10 minutes after the end of unmodified PGE1 administration (paired t-test; P < 0.01), it was maintained over 10 mL/min/100 g until 120 minutes in lipo-PGE1 group. Lipo-PGE1 infusion leads to the objectively measurable improvement and the prolonged action in the blood perfusion of the gastric tube in pigs.

Structural and functional analysis of the apoptosis-associated tyrosine kinase (AATYK) family.

Apoptosis-associated tyrosine kinase (AATYK) is a protein kinase that is predominantly expressed in the nervous system and is involved in apoptosis and neurite growth of cerebellar granule cells. In this study, we cloned three new members of the mouse AATYK family, AATYK1B, AATYK2 and AATYK3. AATYK1B is a splicing variant of the previously reported AATYK1 (referred to as AATYK1A hereafter). In comparison with AATYK1A, these three AATYK members were characterized by having an extra N-terminal region that consists of a signal peptide-like sequence and a predicted transmembrane (TM) region, which is followed by a kinase domain and a long C-terminal domain. Both TM-containing AATYK isoforms (AATYK(+)TM: AATYK1B, 2, and 3) and TM-lacking isoform (AATYK(-)TM: AATYK1A) were recovered in membrane fractions, suggesting that AATYK(+)TM and AATYK(-)TM are transmembrane- and peripheral-membrane protein kinases, respectively. AATYK1A was recovered in the soluble fraction when the cells were treated with 2-bromo palmitate, suggesting that AATYK1A associates with membrane via palmitoylation. The kinase domain was highly conserved among all AATYK members and was shown to be catalytically active. Three AATYK family members were predominantly expressed in adult mouse brains with almost similar expression profiles: widespread distribution over the various brain regions, especially in the cerebellum and hippocampus, and up-regulated expression during development of the cerebellum. In cultured cerebellar granule cells, AATYK1 was abundantly localized in both soma and axons, AATYK2 distribution was restricted to soma, and AATYK3 was punctately present over the cells. AATYK1 was concentrated in the central domain of growth cones of dorsal root ganglion neurons. Our results indicate that AATYK family members are brain-dominant and membrane-associated kinases with slightly different distribution patterns in the developing and adult mouse brain, which may be involved in fine regulation of neuronal functions including neurite extension and apoptosis.

Home-based walking improves cardiopulmonary function and health-related QOL in community-dwelling adults.

The objective of our study was to investigate the effects of a home-based walking program on physical fitness and QOL among community residents. Subjects (n = 200, mean age: 64.2 years, range: 42 - 75 years) who participated in the 32-week trial were randomly allocated to one of two groups: an exercise (E) group and a control (C) group. The E group was instructed to increase the number of steps a day that they walked and to perform aerobic walking at a target heart rate for 20 minutes or more daily, 2 or more days a week. The C group was told to continue their normal level of activity. Outcome measures were the 3-minute shuttle stamina walk test (SSWT), 30-second chair-stand test (CS-30), and SF-36. Increases in SSWT values were significantly greater in the E group than in the C group (men 24.1 m vs. 6.3 m; women 8.8 m vs. 2.4 m), as were increases in CS-30 values (men 5.9 vs. 2.6; women 4.5 vs. - 0.1). On the SF-36, the scores in the E group for vitality and mental health increased significantly. Home-based walking is considered to be an effective and feasible method to improve physical fitness and QOL among community residents.

Positive end-expiratory pressure ventilation increases extravascular lung water due to a decrease in lung lymph flow.

Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the lung lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.

A metastatic haemangiopericytoma of the floor of the mouth.

A case of metastatic haemangiopericytoma in the floor of the mouth is described. Haemangiopericytoma is a relatively rare slow-growing vascular tumour with variable malignant potential. This tumour has been identified in almost every region of the body, but its occurrence in the oral cavity has been rarely reported. The rate of regional and distant metastasis of the tumour is low. This case, presented 12 years after initial surgery suggested the need for careful long-term follow-ups of patients with haemangiopericytoma.

FDTD Simulation of Nonlinear Ultrasonic Pulse Propagation in ESWL.

The extracorporeal shock wave lithotripsy (ESWL) has come into wide use due to its non-invasive advantage. However, as for the shock wave propagation in human body in relation to practical lithotripsy, there are a few studies on numerical simulation based on models conforming to practical situations. In this paper we report a numerical method of finite difference time domain (FDTD) for analyzing ultrasonic pulse nonlinear propagation in human body tissues and demonstrated it through an experiment of Reichenberger's ESWL in water.

Nursing care for dialysis patients in Japan.

In Japan, the number of chronic renal failure patients requiring dialysis treatment is increasing by approximately 10,000 patients a year, totalling 229,538 or 1,801.2 patients per one million population at the end of December, 2002 according to the survey conducted by the Japanese Society for Dialysis Therapy. The primary disease is diabetic nephropathy (28.1% of patients), and with greater numbers of long-term and elderly patients, the incidence and severity of complications continue to increase. Dialysis units provide more diversified care, but budget cuts in health care make it difficult to secure sufficient personnel, and the workload on nurses has intensified. In this study, a survey of 157 out of 300 randomly selected dialysis facilities in Japan was made regarding nursing systems and nurses' concerns for medical care of dialysis patients.

Centrosome hyperamplification and chromosomal damage after exposure to radiation.

OBJECTIVE: In order to elucidate the effects of radiation on centrosome hyperamplification (CH), we examined the centrosome duplication cycle in KK47 bladder cancer cells following irradiation. METHODS: KK47 cells were irradiated with various doses of radiation and were examined for CH immunostaining for gamma-tubulin. RESULTS: Nearly all control cells contained one or two centrosomes, and mitotic cells displayed typical bipolar spindles. The centrosome replication cycle is well regulated in KK47. Twenty-four hours after 5-Gy irradiation, approximately 80% of irradiated cells were arrested in G2 phase, and at 48 h after irradiation, 56.9% of cells contained more than two centrosomes. Laser scanning cytometry performed 48 h after irradiation showed the following two pathways: (1) unequal distribution of chromosomes to daughter cells, or (2) failure to undergo cytokinesis, resulting in polyploidy. With mitotic collection, M-phase cells with CH could be divided into G1 cells with micronuclei and polyploidal cells. Fluorescence in situ hybridization analysis showed clear signs of chromosomal instability (CIN) at 48 h after irradiation. The present study had two major findings: (1) continual duplication of centrosomes occurred in the cell cycle-arrested cells upon irradiation, leading to centrosome amplification; (2) cytokinesis failure was due to aberrant mitotic spindle formation caused by the presence of amplified centrosomes. Abnormal mitosis with amplified centrosomes was detected in the accumulating G2/M population after irradiation, showing that this amplification of centrosomes was not caused by failure to undergo cytokinesis, but rather that abnormal mitosis resulting from amplification of centrosomes leads to cytokinesis block. CONCLUSION: These results suggest that CH is a critical event leading to CIN following exposure to radiation.

Diagnosis of acute brain-stem infarcts using diffusion-weighed MRI.

There are many reports on acute cerebral infarcts diagnosed by diffusion-weighted MRI (DWI), but few describe brain-stem infarcts diagnosed by this method. Using the apparent diffusion coefficient (ADC), we studied 18 consecutive patients with brain-stem infarcts who underwent DWI during the acute phase. We calculated and compared the ADC ratio (lesion ADC/contralateral ADC) in 10 patients with brain-stem and 23 with supratentorial cortical infarcts examined within 24 h of the onset of stroke. Ischaemic brain-stem lesions were detected in all 15 patients who underwent DWI more than 3 h after the onset, but not in two who had DWI within 3 h of the onset; their ADC ratio was more than 0.95. ADC ratios in patients with brain-stem infarcts decreased as the interval between onset and DWI increased; the decrease was slower than in patients with supratentorial cortical infarcts.