Impact of Oral Health Status on Perceived Dental Problems Among Japan Maritime Self-Defense Force Personnel.

INTRODUCTION: Dental problems may have a great impact on military mission effectiveness, as such, evidence-based dental classification guidelines are required for minimizing the occurrence of dental problems. The aim of this study is to elucidate the independent contribution of each oral disease to the perception of dental problems among Japan Maritime Self-Defense Force (JMSDF) personnel in order to make the dental classification guidelines more precise for the prediction of future dental problems. MATERIALS AND METHODS: Japan Maritime Self-Defense Force personnel who were examined during the annual dental checkup in 2013 answered questions about the experience of dental problems within the last 12 months in 2014. The associations between the items of a dental checkup and the perception of dental problems were examined using multiple logistic regression analysis with a stepwise procedure to calculate odds ratios (ORs) and 95% CIs. RESULTS: The data of a total of 22,441 subjects were included in the analysis. Those who declared to have perceived dental problems within the last 12 months were 5,088 (22.7%). The multiple logistic regression analysis showed that personnel who had decayed teeth had a higher chance of experiencing dental problems than those who had no dental caries. Personnel whose periodontal disease was judged to be more severe in a dental examination had a greater OR for the perception of dental problems. CONCLUSION: These results may become recommendations for operations in the JMSDF dental classification system.

Programmed Cell Death-1 Pathway Deficiency Enhances Autoimmunity Leading to Dacryoadenitis of Mice.

Programmed cell death protein (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 in cancer patients. However, the occurrence of autoimmune inflammatory disorders in various organs has been increasingly reported as an adverse effect of nivolumab. Of the disorders associated with nivolumab, Sicca syndrome occurs in 3% to 11% of cases and has unknown pathologic mechanisms. Whether the absence of the PD-1 pathway causes functional and morphologic disorders in lacrimal glands was determined by analyzing PD-1 gene-knockout (Pdcd1-/-) mice. Histopathologic analysis showed that Pdcd1-/- mice developed dacryoadenitis beginning at 3 to 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+ Th-cell subset consisted of Th1 cells producing interferon-γ in an 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 the prevention of autoimmune inflammatory disorders in lacrimal glands caused by activated CD4+ Th1 cells.

Chronic chorioretinal detachment under normal intraocular pressure in eye with uveitic glaucoma after trabeculectomy: A case report.

RATIONALE: Choroidal detachment is a major postoperative complication of trabeculectomy. Postoperative choroidal detachment occurs with low intraocular pressure (IOP), and is naturally resolved by elevation of IOP. We report a case of chronic chorioretinal detachment (CRD) in the eye with uveitic glaucoma after trabeculectomy which persisted with normal IOP resistant for medication and required surgery. PATIENT CONCERNS: A 63-year-old man was referred to our department with uncontrolled uveitic glaucoma in his right eye. At first presentation, IOP was 62 mm Hg in the right eye with opened angle, and active ocular inflammation was presented by moderate cell infiltration to the anterior chamber. DIAGNOSIS: Uveitic glaucoma. INTERVENTIONS: Trabeculectomy with mitomycin-C combined with phacoemulsification were performed without any surgical trouble. Postoperative inflammation in the anterior segment was mild, and IOP decreased to the middle-teen. OUTCOMES: At 19 days after surgery, the depth of the anterior chamber changed to shallow and CRD occurred in the inferior quadrant area. This complication could not be resolved by additional systemic corticosteroid medication and scleral fenestration. Although IOP was maintained in middle-teen range, suture fixation of the sclera flap and additional scleral fenestration were necessary to resolve CRD at 191 days after primary surgery. LESSONS: In uveitic eye with uncontrolled ocular hypertension, severe CRD after trabeculectomy is able to occur even with normal IOP, which requires surgical procedure in addition to the medical treatment.

Scleral buckling versus vitrectomy for young japanese patients with rhegmatogenous retinal detachment in the era of microincision surgery: real-world evidence from a multicentre study in Japan.

PURPOSE: To evaluate real-world evidence for young Japanese patients with rhegmatogenous retinal detachment (RRD) by retrospectively examining surgical procedures and clinical outcomes in the Japan Clinical Retina Study group. METHODS: This was a multicentre retrospective study of the medical records of 562 young patients (384 males and 178 females; mean age: 33.0 ± 11.8 years) who had been diagnosed with RRD and who underwent surgical procedures in participating centres during the period between April 2013 and August 2016. RESULTS: The selected surgeries were scleral buckling (SB) for 295 eyes (49.7%) and pars plana vitrectomy (PPV) for 262 eyes (44.1%). Between the two surgical procedures, there was no significant difference in the primary anatomical reattachment rate (PARR, SB = 92.2%, PPV = 93.9%); improvements in vision were noted in both groups. The incidences of proliferative vitreoretinopathy and cataract formation within 1 year of PPV were 2.3% (p = 0.0047) and 6.5% (p = 0.0005), whereas they were 0% and 1.0% in the SB group, respectively. CONCLUSION: Scleral buckling (SB) and PPV were chosen with almost equal frequency for young patients with RRD. Clinical outcomes for SB and PPV exhibited a similar PARR. The incidence of cataract formation after PPV may constitute an important limitation of the procedure.

Age-related differences in the clinical features of ocular sarcoidosis.

The distribution of age at diagnosis in ocular sarcoidosis has shifted towards the older age groups in developed countries. In systemic sarcoidosis, age-related differences in the clinical presentation, which reflect the therapeutic strategies, was reported. We retrospectively compared 100 consecutive patients from April 2010 to March 2016 who were initially diagnosed with ocular sarcoidosis by International Workshop on Ocular Sarcoidosis criteria. They were classified into elder (>65 years: 50 patients) and younger (≤65 years: 50 patients) groups by the age at diagnosis of uveitis associated with sarcoidosis. All patients received ophthalmic examination to assess the presence of seven intraocular signs and 4 laboratory parameters. Significantly fewer ocular signs (2.8 ± 1.5 and 3.6 ± 1.5; P = 0.0034) and abnormal laboratory results (1.5 ± 1.2 and 2.0 ± 1.2; P = 0.023) were detected in the elder group than in the younger group; statistical differences were found between the groups regarding the frequencies of mutton-fat keratic precipitates (40% and 64%; P = 0.012), vitreous opacities (60% and 78%; P = 0.0059), bilateral inflammation (64% and 80%; P = 0.012), and bilateral hilar lymphadenopathy between the groups (52% and 78%; P < 0.001). Multiple linear regression analysis showed negative correlations between age and number of detected ocular signs (r = -0.36, P < 0.001) and laboratory results (r = -0.20, P = 0.023). The characteristic ocular signs and abnormal laboratory results had a lower frequency in the elder patients compared with the younger patients. Probable or possible ocular sarcoidosis by the international criteria should increase with increased life expectancy in developed countries.

Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese.

BACKGROUND: Gout is a common disease resulting from hyperuricemia which causes acute arthritis. A recent genome-wide association study (GWAS) of gout identified three new loci for gout in Han Chinese: regulatory factor X3 (RFX3), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and breast carcinoma amplified sequence 3 (BCAS3). The lack of any replication studies of these three loci using other population groups prompted us to perform a replication study with Japanese clinically defined gout cases and controls. METHODS: We genotyped the variants of RFX3 (rs12236871), KCNQ1 (rs179785) and BCAS3 (rs11653176) in 723 Japanese clinically defined gout cases and 913 controls by TaqMan method. rs179785 of KCNQ1 is also evaluated by direct sequencing because of difficulties of its genotyping by TaqMan method. RESULTS: Although the variants of RFX3 and BCAS3 were clearly genotyped by TaqMan method, rs179785 of KCNQ1 was not, because rs179785 (A/G) of KCNQ1 is located at the last nucleotide ("A") of the 12-bp deletion variant (rs200562977) of KCNQ1. Therefore, rs179785 and rs200562977 of KCNQ1 were genotyped by direct sequencing in all samples. Moreover, by direct sequencing with the same primers, we were able to evaluate the genotypes of rs179784 of KCNQ1 which shows strong linkage disequilibrium with rs179785 (D' = 1.0 and r 2 = 0.99). rs11653176, a common variant of BCAS3, showed a significant association with gout (P = 1.66 × 10- 3; odds ratio [OR] = 0.80); the direction of effect was the same as that seen in the previous Han Chinese GWAS. Two variants of KCNQ1 (rs179785 and rs179784) had a nominally significant association (P = 0.043 and 0.044; OR = 0.85 and 0.86, respectively), but did not pass the significance threshold for multiple hypothesis testing using the Bonferroni correction. On the other hand, rs200562977 of KCNQ1 and rs12236871 of RFX3 did not show any significant association with gout. CONCLUSION: BCAS3 is a coactivator of estrogen receptor alpha, and the influence of estrogen to serum uric acid level is well known. Our present replication study, as did the previous gout GWAS, demonstrated the common variant of BCAS3 to be associated with gout susceptibility.

Epidemiological patterns of traumatic musculoskeletal injuries and non-traumatic disorders in Japan Self-Defense Forces.

BACKGROUND: The epidemiological patterns of musculoskeletal injuries or disorders in military personnel have not been well documented and a better understanding is required for proper preventative measures and treatment. Here, we investigated musculoskeletal injuries or disorders among members of the Japan Self-Defense Forces. METHODS: All orthopedic patients (n = 22,340) who consulted to Japan Self-Defense Forces Hospitals were investigated for their type of injury or disorder, the injured body part, the mechanism, and the cause of injuries. RESULTS: Thirty-nine percent of the cases were classified as traumatic injuries, and 61% were classified as non-traumatic disorders. Of the traumatic injury patients, the injured body part was the upper extremity in 32%, the trunk in 23%, and the lower extremities in 45% of the cases. The most common injured body location was the knee followed by the hand/finger and ankle. Exercise was the most common cause of injury, followed by traffic accident and military training. Contusions were the most common traumatic injuries, followed by sprains and fractures. Of non-traumatic disorders, the lower extremities were reported as the injured part in 43% of the disorders. Lumbar spine disorders were the most common non-traumatic disorders, followed by tendon and joint disorders. CONCLUSIONS: Over one-third of orthopedic cases among members of the Japan Self-Defense Forces are traumatic injuries, with the knee being the body part most commonly injured and exercise being the leading cause of injury.

Topical Corticosteroid-Resolved Rubeosis Iridis with Neovascular Glaucoma Caused by Noninfectious Granulomatous Uveitis.

PURPOSE: We report a case of topical corticosteroid treatment-resolved rubeosis iridis with neovascular glaucoma (NVG) caused by noninfectious granulomatous uveitis. CASE REPORT: A 61-year-old woman with left ocular pain and blurred vision was referred to our department. Visual acuity and intraocular pressure (IOP) were 20/60 and 37 mm Hg in the left eye, respectively. Inflammatory cells, hyphema, and rubeosis iridis were observed. All laboratory tests, including multiplex polymerase chain reaction for infection using aqueous humor, were negative, and there was neither retinal occlusive vasculitis nor retinal ischemia in the fundus. Our diagnosis was noninfectious granulomatous anterior uveitis-associated NVG. Topical corticosteroid treatment and anti-glaucoma agents resolved inflammation, rubeosis iridis, and NVG. IOP had decreased to 13 mm Hg by 1 month of treatment, and no recurrence was observed. CONCLUSION: Topical corticosteroid could resolve rubeosis iridis and NVG in an eye with noninfectious anterior uveitis. The pathogenesis of NVG in eyes with uveitis is still unknown, but inflammation might have a part in angiogenesis. Anti-inflammatory treatment can be selected as the first choice for anterior uveitis-associated NVG.

Assessment of diagnostic and therapeutic vitrectomy for vitreous opacity associated with uveitis with various etiologies.

Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.

Bilateral idiopathic retinal vasculitis following coxsackievirus A4 infection: a case report.

BACKGROUND: Coxsackieviruses are members of a group of viruses called the enteroviruses, which may cause respiratory and gastrointestinal symptoms, erythema, meningoencephalitis, myocarditis, pericarditis, and myositis. Unilateral acute idiopathic maculopathy caused by coxsackievirus A16 has been associated with hand, foot, and mouth disease, but only a few reports describe retinitis associated with coxsackievirus serotype B3 or B4. We report a case of bilateral multifocal obstructive retinal vasculitis that developed after coxsackievirus A4 infection. CASE PRESENTATION: A 60-year-old woman was referred to our department with bilateral visual disturbance that developed following flu-like symptoms. At the initial examination, best corrected visual acuity was 20/200 in the right eye and 20/50 in the left eye. The critical flicker frequency (CFF) was 23 Hz in the right eye and 27 Hz in the left eye. Fine white keratic precipitates with infiltrating cells were presented in the anterior chamber of both eyes, and multifocal retinal ischemic lesions were observed in the macula and posterior pole of both eyes. The retinal lesions corresponded with scotomas observed in Goldmann visual field test. On spectral domain-optical coherence tomography (SD-OCT), retinal lesions were depicted as hyper-reflective regions in the inner retina layers in both eyes, and disruption of ellipsoid line in the left eye., Fluorescein angiography exhibited findings indicative of multifocal obstructive retinal vasculitis. The patient had a history of current hypertension treated with oral therapy and glaucoma treated with latanoprost eye drops. Blood test for coxsackievirus antibody titers revealed that A4, A6, A9, B1, B2, B3, and B5 were positive (titers: 8-32). Abdominal skin biopsy of necrotic tissue suggested vascular damage caused by coxsackievirus. The general symptoms improved after 6 weeks, and the multifocal retinal ischemic lesions were partially resolved with residual slightly hard exudates. Only coxsackievirus A4 antibody titer increased from 4 to 32-fold after 14 months. However, hyper-reflective regions and disruption of the inner retinal layers on SD-OCT persisted especially in the right eye, and residual paracentral scotoma was observed in the right eye. CONCLUSION: The present case suggests that coxsackievirus A4 causes bilateral multifocal obstructive retinal vasculitis with irreversible inner retinal damage.

Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk.

Gout is caused by hyperuricemia, with alcohol consumption being an established risk factor. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are crucial enzymes for alcohol metabolism. We recently performed a genome-wide association study of gout and a subsequent fine-mapping study which identified rs671 of ALDH2 as a gout locus. However, the association between gout and common variants of ADH1B has hitherto remained unreported, prompting us to investigate the association between gout and common dysfunctional variants of ADH1B (rs1229984) and ALDH2 (rs671). We used 1,048 clinically defined gout cases and 1,334 controls of Japanese male. The "His carrier" (His/His or His/Arg) of rs1229984 (His48Arg) of ADH1B significantly increased gout risk (P = 4.3 × 10-4, odds ratio = 1.76), as did the "non-Lys carrier (Glu/Glu)" of rs671 (Glu504Lys) of ALDH2. Furthermore, common variants of ADH1B and ALDH2 are independently associated with gout. Our findings likewise suggest that genotyping these variants can be useful for the evaluation of gout risk.

Anti-VEGF therapy for central retinal vein occlusion caused by tuberculosis-associated uveitis: a case report.

BACKGROUND: Tuberculosis (TB)-associated uveitis presents periphlebitis, occasionally causing central retinal vascular occlusion (CRVO). Intravitreal injection of ranibizumab (IVR) is an effective treatment for CRVO, which improves macular edema (ME) by reducing vascular permeability and prevents progression of retinal nonperfusion in CRVO. We report a case of CRVO due to TB-associated uveitis, which initially remitted by repeated IVR as an adjunct to anti-TB therapy and systemic corticosteroids, but subsequently led to severe vitreous hemorrhage (VH). CASE PRESENTATION: A 28-year-old man was referred to our hospital with a 2-week history of uveitis in his right eye. Ophthalmoscopic examination of the right eye revealed fine keratoprecipitates and moderate cell infiltration into the anterior chamber and vitreous. No obvious retinal lesion was observed. Despite initiation of topical corticosteroids, CRVO developed a few weeks later in the right eye. TB-associated uveitis was diagnosed based on a positive tuberculin skin test and interferon-γ release assay in addition to the ocular findings. Anti-TB therapy together with IVR and systemic corticosteroids was initiated. Although fundus findings associated with CRVO gradually improved, CRVO with VH recurred before the fourth IVR. Although IVR was continued, VH progressed to obscure fundus observation. Therefore, vitrectomy and panretinal photocoagulation were performed. After surgery, ocular inflammation was controlled, and anti-TB therapy was continued for 6 months and was suspended. CONCLUSION: In addition to anti-TB therapy with or without corticosteroids, panretinal photocoagulation for retinal nonperfusion area in TB-associated uveitis should be performed for preventing neovascularization that may cause VH, and this role of panretinal photocoagulation cannot be replaced by anti-VEGF therapy.

Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy.

Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid.

Association of High-Mobility Group Box-1 With Th Cell-Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients.

Purpose: High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines. Methods: The study group consisted of 24 patients with ocular sarcoidosis. The control group consisted of 27 patients with proliferative diabetic retinopathy (PDR) and 24 with idiopathic epiretinal membrane (ERM). Vitreous fluid samples were obtained at the beginning of vitrectomy. Vitreous levels of HMGB1 and IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα were measured. Results: High-mobility group box-1 was detected in the vitreous of 23 of 24 patients (95.8%) with ocular sarcoidosis. Mean vitreous level of HMGB1 was the highest in the sarcoidosis group, followed by the PDR and ERM groups, with significant differences between the three groups. In the sarcoidosis group, vitreous levels of IL-6, IL-10, IL-31, IFN-γ, sCD40L, and TNFα were significantly higher than those in the idiopathic ERM group, and IFN-γ and sCD40L were significantly higher than those in the PDR group. Vitreous HMGB-1 level correlated significantly with IL-10, IFN-γ, and sCD40L levels but not with IL-6, IL-17, IL-31, or TNFα levels. Conclusions: The vitreous level of HMGB1 is elevated in ocular sarcoidosis and is associated with vitreous levels of Th1- and regulatory T-related cytokines, but not with proinflammatory or Th17-related cytokines.

Renoprotective effects of a dipeptidyl peptidase 4 inhibitor in a mouse model of progressive renal fibrosis.

Although the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond their hypoglycemic action have been reported, whether these inhibitors have renoprotective effects in nondiabetic chronic kidney disease (CKD) is unclear. We examined the therapeutic effects of DPP-4 inhibition in mice with unilateral ureteral obstruction (UUO), a nondiabetic model of progressive renal fibrosis. After UUO surgery, mice were administered either the DPP-4 inhibitor alogliptin or a vehicle by oral gavage once a day for 10 days. Physiological parameters, degrees of renal fibrosis and inflammation, and molecules related to renal fibrosis and inflammation were then evaluated using sham-operated mice as controls. Positive area of α-smooth muscle actin was significantly smaller and expression of transforming growth factor ß messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group. Renal total collagen content was also significantly lower in the alogliptin-treated group than in the vehicle-treated group. These results suggest that alogliptin exerted renoprotective antifibrotic effects. The positive area of F4/80 was significantly smaller and expression of CD68 messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group, suggesting an anti-inflammatory action by the DPP-4 inhibitor. Compared to the results for the vehicle-treated group, expression of markers for M1 macrophages tended to be lower in the alogliptin-treated group, and the relative expression of M2 macrophages tended to be higher. These data indicate the various protective effects of DPP-4 inhibition in nondiabetic mice with UUO. DPP-4 inhibitors may therefore be promising therapeutic choices even for nondiabetic CKD patients.

Evaluation of Efficacy and Safety of Latanoprost/Timolol versus Travoprost/Timolol Fixed Combinations for Ocular Hypertension Associated with Uveitis.

PURPOSE: To compare latanoprost/timolol (LT) versus travoprost/timolol (TT) fixed combinations for ocular hypertension (OHT) associated with uveitis. METHODS: Thirty-six patients (55 eyes) who were treated with LT (28 eyes) or TT (27 eyes) for OHT associated with uveitis were reviewed retrospectively. Intraocular pressure (IOP) and inflammation scores at the initiation of treatment and at the last visit during therapy were analyzed. RESULTS: Although IOP was reduced significantly in both LT and TT groups, the reduction rate was significantly greater with TT group than with LT. The differences in the reduction of IOP between the groups remained significant when the cases were classified into inflammation-induced OHT and steroid-induced OHT. Inflammation score was not exacerbated by LT or TT treatment. CONCLUSIONS: Both LT and TT are safe and effective for the treatment of OHT associated with uveitis and greater IOP reduction may be achieved by TT than by LT treatment.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. RESULTS: In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10-8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10-8). CONCLUSIONS: Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.

Cationic Lipid Content in Liposome-Encapsulated Nisin Improves Sustainable Bactericidal Activity against Streptococcus mutans.

An oral infectious disease, dental caries, is caused by the cariogenic streptococci Streptococcus mutans. The expected preventive efficiency for prophylactics against dental caries is not yet completely observed. Nisin, a bacteriocin, has been demonstrated to be microbicidal against S. mutans, and liposome-encapsulated nisin improves preventive features that may be exploited for human oral health. Here we examined the bactericidal effect of charged lipids on nisin-loaded liposomes against S. mutans and inhibitory efficiency for insoluble glucan synthesis by the streptococci for prevention of dental caries. Cationic liposome, nisin-loaded dipalmitoylphosphatidylcholine/phytosphingosine, exhibited higher bactericidal activities than those of electroneutral liposome and anionic liposome. Bactericidal efficiency of the cationic liposome revealed that the vesicles exhibited sustained inhibition of glucan synthesis and the lowest rate of release of nisin from the vesicles. The optimizing ability of cationic liposome-encapsulated nisin that exploit the sustained preventive features of an anti-streptococcal strategy may improve prevention of dental caries.

Incidence and Characteristics of Traumatic Shoulder Instability in Japanese Military Cadets.

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.

The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression.

Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10(-19); risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 × 10(-12)).