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Little is known regarding the incidence of the shoulder instability in Japan. The aim of this study was to evaluate the incidence of traumatic shoulder instability among Japanese military cadets. A prospective cohort study was performed to capture all traumatic shoulder instability events between 2009 and 2012 among cadets in a military educational academy of the Japan Self Defense Forces. The total number of cadets in the cohort was 5,402 (average age 20.6 years). The incidence of instability events, including dislocation or subluxation, was calculated. Chronicity, demographics of participants, mechanism of injury, and athletic events were also evaluated. The incidence of traumatic dislocation was 4.1/1,000 person-years and that of subluxation was 6.1/1,000 person-years. The incidence of primary dislocation or subluxation was 5.4/1,000 person-years and that of recurrent dislocation or subluxation was 4.7/1,000 person-years. Of first dislocations or subluxations, 92% occurred during sports activities, including after-school sports activities, military training, and gym classes. In conclusion, the overall incidence of shoulder instability events among Japanese military cadets was 10.3/1,000 person-years, and was extremely high. Most shoulder instability events occurred during sports activities, and a program to prevent such injuries during sports activities is necessary for young participants.

Plasmin has recently been reported to be associated with renal fibrosis in experimental models, but its role in human renal diseases is unclear. Fifty-seven patients with IgA nephropathy (IgAN) were evaluated retrospectively. Plasmin in their renal biopsy tissues was assessed by in situ zymography using a plasmin-sensitive synthetic peptide, and the relationships between patients’ histologic or clinical parameters and their renal plasmin activity [assessed semiquantitatively by calculating the positively stained percentage of the total tubulointerstitial (TI) area] were evaluated. Plasmin activity was observed almost exclusively in the TI space (mainly in the interstitium and partly in the tubular epithelial cells) and was significantly stronger in patients with TI lesion (tubular atrophy/interstitial fibrosis and tubulointerstitial inflammation) than in those without TI lesion. It was significantly and positively correlated with the global glomerulosclerosis rate and significantly and negatively correlated with estimated glomerular filtration rate not only at the time of renal biopsy but also at the end of the follow-up period. Double stainings for plasmin activity and inflammatory cells, cytokeratin, or α-smooth muscle actin (α-SMA) in selected patients revealed TI infiltration of inflammatory cells, attenuated tubular epithelial expression of cytokeratin, and augmented interstitial expression of α-SMA close to upregulated plasmin activity in the TI space. These data suggest that TI plasmin is associated with TI inflammation leading to renal fibrosis, and can cause the decline in renal function seen in patients with IgAN. Reducing plasmin in situ may therefore be a promising therapeutic approach slowing renal fibrogenesis and improving renal function.

The protective effects of Rho kinase inhibitor fasudil against renal diseases have recently been reported. We compared the therapeutic effects of fasudil on the spontaneously hypercholesterolemic (SHC) rat, a model of chronic kidney disease (CKD) with proteinuria, with those of the angiotensin receptor blocker olmesartan (OL) by paying attention to the proteinuria and the macrophage phenotype. SHC rats were allocated to six treatment groups: a vehicle (Ve) group, a low-dose fasudil (FL) group, a high-dose fasudil (FH) group, an OL group, a combination of low-dose fasudil and OL (CL) group, and a combination of high-dose fasudil and OL (CH) group. Sprague-Dawley rats treated with vehicle served as a control (n= 7/each). The rats were treated for 24 wk. Compared with the Ve group, proteinuria was significantly decreased in the FH, OL, and CL groups, and it completely disappeared in the CH group. Glomerular stainings of nephrin and F-actin were focally impaired in the Ve group but were restored in the CH group. Western blotting showed that the CH group had significantly increased renal nephrin expression compared with the Ve group. Interstitial infiltration of macrophages was significantly increased in the Ve group, which was significantly attenuated in all treatment groups. The ratio of CD206 (M2 macrophage marker) to CD68 mRNA was significantly greater in the CH group than in the Ve group. These results indicate that fasudil with OL reduces proteinuria by protecting podocyte integrity and alters the interstitial macrophage density/phenotype, thereby exerting renoprotective effects against CKD.

ABSTRACTObjectives:Establishing containment measures against the potential spread of the smallpox virus has become a major issue in the public health field since the 2001 anthrax attacks in the United States. The primary objective of the study was to investigate the relationship between the level of activity of public health agencies and the voluntary cooperation of residents with ring-vaccination measures against a smallpox epidemic.Methods:A discrete-time, stochastic, individual-based model was used to simulate the spread of a smallpox epidemic that has become a more pressing topic due to 9/11 and to assess the effectiveness of and required resources for ring-vaccination measures in a closed community. In the simulation, we related sensitive tracing to the level of activity of the public health agency and strict isolation to the level of voluntary cooperation from residents.Results:Our results suggest that early and intensive case detection and contact tracing by public health agencies can reduce the scale of an epidemic and use fewer total resources. In contrast, voluntary reporting by the traced contacts of symptom onset after vaccination had little impact on the scale of epidemic in our model. However, it reduced the total required resources, indicating that citizens' voluntary cooperation would contribute to reducing the burden on public health agencies.Conclusions:We conclude that a combined effort on the part of public health agencies and residents in performing containment measures is essential to quickly ending a smallpox epidemic.(Disaster Med Public Health Preparedness. 2012;6:270–276)

Introduction: Cardiovascular diseases can lead to sudden in-flight in- capacitation and long-term disability in aircraft pilots. Electrocardiogram (ECG) has been widely used to screen for these diseases in routine aeromedical examinations. Several ECG changes such as complete left bundle-branch block (CLBBB) and left ventricular hypertrophy (LVH) have been associated with increased likelihood of underlying structural car- diac diseases in addition to the emergence of newly recognized cardio vascular diseases such as Brugada syndrome. Therefore, the purpose of this study was to analyze decadal ECG changes in aircraft pilots between 40 and 50 yr in order to make an appropriate evaluation of these ECG changes. Methods: We analyzed the ECGs from the annual aeromedical examination of age 50 compared to those 40 yr of age in a total of 176 Japan Air Self-Defense Force pilots. Results: With regard to decadal changes, we detected 34 new ECG changes (1 of sinus tachycardia, 8 sinus bradycardia, 1 atrial fibrillation, 2 premature atrial contraction, 1 premature ventricular contraction, 2 left axis deviation, 6 first-degree atrioventricular block, 1 CLBBB, 3 complete right bundle-branch block, 2 incomplete right bundle-branch block, 1 right ventricular conduction delay, and 6 LVH). Although the majority of them were concluded to be normal variants, the results of echocardiography in two hypertensive pilots without good control demonstrated abnormalities: one had mild hypertrophic nonobstructive cardiomyopathy and another had heart en largement. Conclusion: Thus, this study recommends additional cardio vascular examinations, including echocardiography for hypertensive pilots with ECG changes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have reported on the effects of the energy expenditure estimated from the frequency of exercise on bone mass, bone metabolic marker and bone related hormones in young females. The goal of this study is to examine the indices related to bone metabolism such as the bone metabolism markers and hormones and clarify their association with the bone mass through their relationship to exercises. Methods: A total of 190 premenopausal Japanese females aged 20–49 years participated in this study. The calcaneus stiffness index (SI) was measured by ultrasound bone densitometry. The subjects’ past and present exercise was measured using the self-administered questionnaire. Urinary deoxypyridinoline (DPD), 1,25-dihydroxyvitamin D3, intact parathyroid hormone (PTH), and bone specific alkaline phosphatase (BAP) were determined. Results: DPD was shown to be a strong negative predictor of the SI (p < 0.05). Energy expenditure by exercise only during senior high school in the exercise history was shown to be a positive predictor of the SI (p < 0.05). Energy expenditure by exercise only during senior high school was shown to be a significant negative predictor of the DPD (p < 0.05). Conclusion: It has been revealed that the amount of energy expenditure from physical activity during the subject’s high school years affects the levels of SI and DPD in adulthood.

Ventrictcular fibrillation diagnoses such as Brugada syndrome pose a risk of sudden incapacitation or death in aircrew. This case report presents a 44–yr–oId male fighter pilot who unexpectedly developed ventricular fibrillation (VF) during an electrophysiological study (EPS) prior to therapy for non–sustained ventricular tachycardia (nsVT). The nitial aeromedical disposition for this case was "qualified for flying duties," with the restriction that he must fly with another pilot due to repeatedly observed nsVT. This pilot wanted to return to flight duty in single–seat aircraft without any restrictions. Therefore, this patient decided to undergo catheter therapy for nsVT. Unexpectedly, not VT but VF was induced by catheter manipulation during EPS. Pilsicainide–induced coved–type ST wave elevation consistent with Brugada syndrome was noted in this patient's electrocardiogram. He was ultimately disqua!ified due to the diagnosis of VF. This report suggests EPS on rare occasions may uncover another severe disease similar to this case report. [ABSTRACT FROM AUTHOR]

Authors use magnetron sputtering technique for controlling the film composition by modifying the magnetic field with an external solenoid in addition to the magnetic field with a permanent magnet on back of composite target. It is necessary to understand the contribution of the solenoid quantitatively for the effective application of this technique. The magnetic field changes by the solenoid current on the target were calculated by the finite element method (FEM), and compared with the film composition. As the solenoid current increases, magnetic tunnel region on the target (correspond with the well sputtered region by the confined plasma) moves to the centre of the target. The behaviour corresponds with the actually formed film composition. The calculated results also give an information to design the composite target and the correction value for using the already eroded target.

Abstract: Background: The burgeoning costs of nursing care and medical treatment have become a serious problem for Japan, a country with an aging population and declining birthrate. Disease prevention and control of runaway health care costs are two important issues. We are interested in osteoporosis in the elderly. Thus, we aimed to establish predictive factors of low bone mass or fracture in postmenopausal elderly women by means of a simple questionnaire. Methods: Subjects were 107 postmenopausal Japanese women. All data in the present study were collected in 2006. The calcaneus stiffness index (SI) was determined by ultrasound bone densitometry. Urinary deoxypyridinoline (DPD), a marker of bone resorption, was measured. Factors related to bone loss and fracture were investigated by means of a questionnaire and tested by regression analysis and analysis of variance. Results: The SI correlated significantly with age, years since menopause, weight, and the DPD level. Change in body weight did not influence the SI, but lumbar pain, height loss, and stoop did influence the SI. The SI was significantly low in subjects who had already suffered a fracture. Body mass index (BMI) was the strongest predictor of the SI. Conclusion: Low bone mass or fracture may be predicted in part with a simple questionnaire that addresses personal factors related to bone health.

Introduction: Cardiovascular diseases can cause sudden incapacitation in aircrew. Cardiological diagnosis and therapy have changed a great deal in recent decades, as with coronary revascularization, including percutaneous coronary intervention and coronary artery bypass grafting for coronary artery disease, and electrophysiological studies and radiofrequency catheter ablation (RFCA) for sustained arrhythmias. Physicians need to be able to make appropriate, objective recommendations regarding cardiovascular diseases in an aeromedical waiver system. Methods: We analyzed all 95 waiver cases regarding cardiovascular diseases in the Japan Air Self-Defense Force OASDF), 1980-2007, and compared them to policies in the United States Air Force (USAF). Results: The JASDF and the USAF handle most conditions similarly, although there are differences regarding coronary revascularization, atrial fibrillation, non-sustained ventricular tachycardia (nsVT), and hypertrophic cardio-myopathy. The JASDF used RFCA more commonly for the treatment of aircrew with atrial fibrillation and nsVT. Although routine follow-up with electrophysiological studies is no longer indicated for Wolff-Parkinson- White and atrioventricular node reentrant tachycardia in USAF policy, the IASDF still conducts reevaluation for all RFCA cases. Conclusion: This study made recommendations to improve the JASDF waiver system for cardiovascular diseases [ABSTRACT FROM AUTHOR]

The profibrotic effect of plasminogen activator inhibitor-1 (PAI-1) in renal fibrosis is widely recognized, but its mechanism remains controversial especially in chronic progressive kidney disease. In the present study, pioglitazone (Pio) and candesartan (CD), which are reported to inhibit PAI-1, were administered to spontaneously hypercholesterolemic (SHC) rats, a model of chronic progressive kidney disease. Therapeutic effects and effects on the intrarenal plasmin cascade were examined. Eight-wk-old SHC rats were used as controls. Oral administration of vehicle alone, Pio, or CD was performed starting at 8 wk of age and was continued for 24 wk. The degree of renal fibrosis was evaluated by sirius red staining of kidney sections and by total collagen assay of renal homogenates. The renal PAI-1 protein level was assessed by Western blotting, and plasmin activity was analyzed by chromogenic assay and casein gel zymography. Urinary protein and blood urea nitrogen were significantly increased in the vehicle-treated group, but the increase was attenuated in the Pio- and CD-treated groups. This correlated well with the degree of fibrosis as assessed by sirius red staining and total collagen assay. The PAI-1 protein level was also increased significantly in the vehicle-treated group, and the increase was attenuated in the Pio- and CD-treated groups. Despite the presumed plasmin-inhibitory function of PAI-1, plasmin activity changed in parallel with PAI-1. These results suggest that Pio and CD inhibit PAI-1 and exert renoprotective effects against chronic progressive renal disease, but its action is independent of the regulatory function on plasmin activity.

Few studies have investigated the relation between glucose tolerance status and ultrasonographically determined gallstone disease. Using a 75-g oral glucose tolerance test, we examined the association of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) with gallstone disease in Japanese men. Subjects were men aged 48 to 59 of the Japan Self-Defense Forces who received a preretirement health examination between October 1986 to December 1994. After exclusion of 12 men under insulin treatment in the consecutive series of 7637 men, 174 were found to have gallstones; 103 were at the state of postcholecystectomy, and 6899 had normal gallbladder. IGT and NIDDM were associated with a modestly increased risk of gallstone disease; adjusted odds ratios were 1.3 (95% confidence interval [CI]: 0.9–1.8) for IGT and 1.3 (95% CI: 0.8–2.0) for NIDDM after adjustment for hospital, rank, smoking, alcohol use, and body mass index. Adjusted odds ratio for IGT and NIDDM combined was 1.3 (95% CI: 1.0–1.7, p=0.08). When prevalent gallstones and postcholecystectomy were considered separately, NIDDM showed a significant, positive association with postcholecystectomy, but not with prevalent gallstones. The findings add to evidence that glucose intolerance is associated with a modest increase in the risk of gallstone disease.

Gender-related differences in anthropometry, blood biochemistry, psychological parameters, and energy intake during prematch weight reduction were studied in 22 men and 7 women college judoists who lost weight by combining judo training, restricting food and fluid, and sweating. Body weight (BW) decreased significantly by 2.2±1.4 kg in men and 2.0±1.4 kg in women 2 weeks after weight reduction started — not significandy different. Body fat, relative body fat and total energy intake also decreased significandy in both groups 2 weeks after weight reduction started. Lean body mass decreased significandy 2 weeks after weight reduction started only in men. Men had significantly decreased blood lipids, immunoglobulins, complements, hematocrit, white blood cell count, and serum electrolytes, and significant increases in blood uric nitrogen, creatinine, and hemoglobin, while women showed no such changes. The score for vigor in the Profile of Mood States (POMS) decreased in both groups 2 weeks after weight reduction started, but with no statistically gender difference. In women, scores for anxiety in the State-Trait Anxiety Inventory (STAI) and confusion in POMS increased significandy. Although the men and women had the same BW reduction, significant physical stress response was seen only in men, and psychological stress due to weight reduction and mental pressure of an upcoming competition were seen more in women.

Background. Although recent reports show a worldwide increase in allergic diseases during the past 10– years, few epidemiological studies on secular trend and the age-specific prevalence of allergic rhinitis have been carried out in Japan. We conducted a study to clarify the age-specific prevalence of allergic rhinitis and cedar pollinosis to provide baseline data for a prospective study and to investigate the association of rhinitis with both environmental and personal factors among 2,307 Japanese men.

1. The role of endogenous prostaglandins in the antihypertensive mechanism of the angiotensin converting enzyme inhibitor, captopril, was investigated. 2. An unequivocal reduction in blood pressure and significant increase in plasma renin activity and urinary prostaglandin E excretion were found after the captopril administration. 3. The changes in blood pressure, plasma renin activity and urinary prostaglandin E excretion induced by captopril were reversed after the inhibition of endogenous prostaglandin synthesis by indomethacin. However, the responses in low renin hypertension were different from those in normal renin hypertension. 4. In low renin hypertensive patients who responded to captopril, the hypotensive effect was abolished after the addition of indomethacin, whereas no marked change in blood pressure was induced by indomethacin in normal renin hypertensive patients. In contrast, plasma renin activity was markedly increased after captopril administration in normal renin hypertension, and no significant change was found in low renin hypertension. 5. Potentiation of the prostaglandin system seems to be a principal factor in the antihypertensive mechanism of captopril in low renin hypertension, and inhibition of the renin-angiotensin system is important in normal renin hypertensives. 6. The increase in renin release after the administration of captopril was inhibited by indomethacin, suggesting that an endogenous prostaglandin system may contribute to the short feedback mechanism of renin release.

The study aims to examine the relationship between habitual coffee consumption and blood pressure. The subjects were 3336 male self-defense officials aged 48–56 years, who received a preretirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and December 1992. Average coffee intake in the past year was ascertained by a self-administered questionnaire. A significant inverse relation between habitual coffee consumption and blood pressure was found with and without adjustment for alcohol use, cigarette smoking, body mass index, glucose tolerance, and green tea intake. Green tea, another major source of caffeine intake in Japanese, was unrelated to blood pressure. The adjusted mean differences per cup of coffee consumed per day were −0.6 mmHg (95% confident interval [CI]: −0.9 to −0.3, p=0.0001) in systolic blood pressure and −0.4 mmHg (95% CI: −0.5 to −0.2, p=0.0002) in diastolic blood pressure. Habitual coffee drinkers had lower blood pressure than non-drinkers at any levels of alcohol use, cigarette smoking, obesity, and glucose intolerance. Our findings consolidate the previous observation that habitual coffee consumption was associated with lower blood pressure.

We investigated the independent associations of total and beverage-specific ethanol consumption with body mass index (BMI) and waist-to-hip ratio (WHR) in middle-aged Japanese males, because of the scarcity of epidemiologic data in Japan. The subjects were 2227 male self-defense officials who received a pre-retirement health examination at the Self-Defense Forces Fukuoka, Kumamoto, and Sapporo Hospitals. Data on alcohol intake, smoking, physical activity, and past medical history were obtained from a self-reported questionnaire. Height, weight, and waist and hip girth measurements were obtained at the examination. Multiple linear regression analysis was employed. Alcohol intake was positively and strongly associated with WHR (p = 0.0001), but not associated with BMI after adjustment for lifestyle variables, including either BMI or WHR. Subjects who consumed 15 ml per day or more of shochu ethanol showed a larger WHR than never drinkers, and a dose-response relationship was found. Dose-response relationships to other beverages were not found. Dose-response relationships to other beverages were not found. These findings suggest that alcohol intake is strongly and independently associated with WHR, but not with BMI. Abdominal obesity was positively associated with shochu ethanol, but not with other types of alcohol.

Objective.Recently, genetic analyses indicated the association between gout and cGMP-dependent protein kinase 2 (cGKII/PRKG2) gene in a Fukien-Taiwanese heritage population. However, no replication study has been reported in other ancestries. Therefore, we investigated this association in a Japanese population.Methods.Genotyping of 4 variants (rs11736177, rs10033237, rs7688672, and rs6837293) of cGKIIwas performed in 741 male gout patients and 1302 male controls.Results.cGKIIvariants have no association with gout.Conclusion.Our replication study suggests that cGKIIis not involved in gout susceptibility.

Programmed cell death-1 (PD-1) is a coinhibitory molecule that suppresses immune response and maintains immune homeostasis. Moreover, the PD-1 pathway blocks cancers from being attacked by immune cells. Anti-PD-1 antibody therapy such as nivolumab improves survival of cancer patients. However, the occurrence of autoimmune inflammatory disorders in various organs has been increasingly reported as an adverse effect of nivolumab. Among them, sicca syndrome occurs in 3-11% with unknown pathological mechanisms. We examined whether absence of PD-1 pathway causes functional and morphological disorders in lacrimal glands by analysing PD-1 gene-knockout (Pdcd1-/-) mice. Histopathological analysis showed that Pdcd1-/-mice developed dacryoadenitis beginning at 3-4 months of age, and deteriorated with age. Flow cytometric analysis confirmed that cells infiltrating the affected lacrimal glands consisted mainly of CD3+T cells and only a small proportion of CD19+B cells. Among infiltrating T cells, the CD4+helper T cell subset consisted of Th1 cells producing IFN-γ in early stage of dacryoadenitis in Pdcd1-/-mice. Experiments of lymphocyte transfer from Pdcd1-/-into irradiated wild-type mice confirmed that CD4+T cells from Pdcd1-/-mice induced dacryoadenitis. These results indicate that PD-1 plays an important role in prevention of autoimmune inflammatory disorders in lacrimal glands caused by activated CD4+Th1 cells.

Dysfunctional genotype combinations of polymorphic adenosine 5′-triphosphate–binding cassette transporter gene ABCG2/BCRP, which encodes a high-capacity urate secretion transporter in human gut and kidney, are major causes of gout.