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Fragility fractures (FFxs), which are a common musculoskeletal injury in older adults, is associated with an increased frequency of falls. Both FFxs and falls may result from drugs, habits, and co-occurring diseases. We aimed to evaluate the effects of various diseases on the risk of FFx. This retrospective study included 1420 individuals aged ≥60 years. We evaluated the history of clinical FFx and diseases using a detailed questionnaire and a health examination. The risk of comorbidities was assessed using the Age-Adjusted Charlson Comorbidity (AAC) Index. We performed binary logistic regression analysis to determine the risk of FFx and falls after adjusting for covariates. In elderly men, the incidence of FFx positively correlated with rheumatoid arthritis and parent’s hip fracture. For elderly women, the incidence of FFx positively correlated with rheumatoid arthritis and antihypertensive drugs but was inversely associated with dyslipidemia and antilipidemic drugs. The FFX risk of older adults with an AAC Index ≥6 was higher than those with an AAC Index of 1–3. In addition, the AAC Index and falls were independently and strongly associated with a higher risk of FFx. Taken together, multimorbidity increases the risk of clinical FFx independent of falls in the community-dwelling elderly population.

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross-sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic characteristics, past work history, lifestyle-related factors and medical history, compared with non-drinkers, mild drinkers (

Background Varicose veins (VVs) cluster in families, but the familial risk of VVs has not been determined among adoptees. The aim was to estimate whether the familial transmission of VVs is related to disease in biological and/or adoptive parents. Study Design The Swedish Multi-Generation Register and the Swedish Patient Register were used to follow all Swedish-born adoptees (born 1932 through 2004) that could be linked to both their biological and their adoptive parents (n = 80,214; 50% females). The risk of VVs was estimated in adoptees with at least 1 biological parent with VVs, but no adoptive parent with VVs (n = 187) compared with adoptees without a biological or adoptive parent with VVs (n = 1,758). The risk of VVs was also determined in adoptees with at least 1 adoptive parent, but no biological parent with VVs (n = 87), and in adoptees with both biological and adoptive parents affected (n = 21). Results Adoptees from an affected biological parent, but no adoptive parent, were more likely to have VVs than adoptees from an unaffected biological or adoptive parent (standard incidence ratio [SIR] = 2.21; 95% CI, 1.91–2.55). The familial SIR for adoptees with both an affected biological parent and an adoptive parent was 4.58 (95% CI, 2.83–7.01). Adoptees with an affected adoptive parent but no biological parent were not at increased risk of VVs (SIR = 1.15; 95% CI, 0.92–1.42). Conclusions These novel findings suggest that genetic factors make a strong contribution to the familial transmission of VVs from parents to offspring, although familial environmental factors might contribute.

ObjectivesTo clarify the surgical methods and the clinical results of subfascial endoscopic perforator surgery in Japan.MethodsThis study included 1287 limbs of 1091 patients who underwent subfascial endoscopic perforator surgery in 14 hospitals. Simultaneous saphenous vein treatment was performed in 1079 limbs (83.8%), and 118 limbs (9.2%) had deep venous lesions. The venous clinical severity score was calculated before and 6 to 12 months after surgery. The ulcer healing rate and ulcer recurrence rate were calculated cumulatively.ResultsPreoperative venous clinical severity score was significantly decreased from 10.0 ± 6.6 to 3.1 ± 3.4 ( P ConclusionThese results indicate that subfascial endoscopic perforator surgery is an alternative to improve the long-lasting disease severity and/or clinical outcome.

In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation) and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS) and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012-2013. QUS value was expressed as a proportion of the young adult mean (%YAM), with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas.

Background Carbamazepine (CBZ), which is widely used in management of epilepsy or neuropathic pain, causes fatal severe cutaneous adverse reactions (SCARs). CBZ-induced SCARs are known to occur in strong association with human leukocyte antigen (HLA)-A*31:01 in Japanese and European populations. HLA genotyping is currently used to detect human HLA-A*31:01 . Objective To establish a simple and rapid screening assay specific for HLA-A*31:01 , the loop-mediated isothermal amplification (LAMP) method was employed on a sample Japanese population. Methods A set of LAMP primers targeting exon 2 of HLA-A*31:01 were designed. Thirty-two clinical samples including the representative HLA-A allele in Japan were used to assess the specificity of LAMP primers in the detection of HLA-A*31:01 . Results The HLA-A*31:01 -specific LAMP assay showed consistency with polymerase chain reaction reverse sequence-specific oligonucleotide probe (PCR-rSSO) and polymerase chain reaction-sequence based typing (PCR-SBT) results. Conclusion High sensitivity and specificity of the HLA-A*31:01 LAMP assay was confirmed. Considering its convenience, the assay can be widely used to screen patients at high genetic risk of CBZ-induced SCARs.

We purified two isozymes of coniferyl alcohol dehydrogenase (CADH I and II) to homogeneity from cell-free extracts of Streptomyces sp. NL15-2K. The apparent molecular masses of CADH I and II were determined to be 143 kDa and 151 kDa respectively by gel filtration, whereas their subunit molecular masses were determined to be 35,782.2 Da and 37,597.7 Da respectively by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Thus, it is probable that both isozymes are tetramers. The optimum pH and temperature for coniferyl alcohol dehydrogenase activity were pH 9.5 and 45 °C for CADH I and pH 8.5 and 40 °C for CADH II. CADH I oxidized various aromatic alcohols and allyl alcohol, and was most efficient on cinnamyl alcohol, whereas CADH II exhibited high substrate specificity for coniferyl alcohol, and showed no activity as to the other alcohols, except for cinnamyl alcohol and 3-(4-hydroxy-3-methoxyphenyl)-1-propanol. In the presence of NADH, CADH I and II reduced cinnamaldehyde and coniferyl aldehyde respectively to the corresponding alcohols.

Background: A recent study has shown that the measurement of specific IgE antibodies to B-cell epitope peptides of wheat ω-5 gliadin (Pep A) and high molecular weight glutenin subunit (Pep B) are useful to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA). Aims of the study: We sought to compare the sensitivity and specificity of the in vitro tests for measuring the specific IgE antibodies to recombinant ω-5 gliadin (rω-5 gliadin) with those for wheat, gluten, Pep A, and Pep B in identification of patients with WDEIA. Methods: Fifty patients with WDEIA, 25 healthy subjects and 25 patients with atopic dermatitis with specific IgE antibodies to wheat but without experience of allergic reactions after ingestion of wheat products were enrolled in this study. The concentrations of specific IgE antibodies were measured using ImmunoCAPTM. The empirical receiver operating characteristics curves (ROC) for each test were prepared and the areas under the ROC curve (AUC) were compared. Results: In patients with WDEIA, the sensitivities of the allergen-specific IgE tests for wheat, gluten, Pep A, Pep B and rω-5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to rω-5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for rω-5 gliadin. Conclusions: Measuring the concentration of specific IgE antibodies to rω-5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.

There is increasing evidence of an association between residential environments and hypertension. As shown in our previous study, the inconvenience of the locations of residential areas may be one of the factors influencing the blood pressures of inhabitants. Salt intake is one of the likely mediators between inconvenience and hypertension. Therefore, in this study, we evaluated the association between the altitudes of residential areas and salt intake in a rural Japanese region because altitude may be one of the proxies for inconvenience. In this cross-sectional study, 1016 participants living in a mountainous region in Japan were recruited during health examinations. The altitude of each participant's residence was estimated using a geographic information system. Subjects were divided into quartile groups according to the altitudes of their residences. To evaluate salt intake, we employed the 24-h salt intake estimation of Kawano et al. (e24-h salt intake) and the urinary sodium-to-potassium ratio (uNa/K). Linear regression analyses indicated that altitude was an independent factor influencing both e24-h salt intake and uNa/K after adjustments for age, sex, body mass index, physical activity, alcohol consumption, triglycerides and county of residence. The same result was observed when the subjects who did not take antihypertensive medications were analyzed (N=633). The present study indicated that altitude of residence had a significant positive influence on salt intake in a rural area of Japan.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe IgE-mediated allergic reaction provoked by the combination of wheat-ingestion with intensive physical exercise over the next few hours. Among wheat proteins, omega-5 gliadin, which is one of the components of fast omega-gliadin, has been reported as a major allergen in the anaphylaxis. In this study, we detected IgE-binding epitopes within the primary sequence of omega-5 gliadin using arrays of overlapping peptides synthesized on derivatized cellulose membranes. Sera from four patients with WDEIA having specific IgE to the fast omega-gliadin were used to probe the membrane. Seven epitopes, QQIPQQQ, QQLPQQQ, QQFPQQQ, QQSPEQQ, QQSPQQQ, QQYPQQQ, and PYPP, were detected within the primary sequence of omega-5 gliadin. By using sera of 15 patients, 4 of them, QQIPQQQ, QQFPQQQ, QQSPEQQ, and QQSPQQQ, were found to be dominant epitopes. Mutational analysis of the QQIPQQQ and QQFPQQQ indicated that amino acids at positions Gln(1), Pro(4), Gln(5), Gln(6), and Gln(7) were critical for IgE binding. These results will provide a useful tool for developing safer wheat products in addition to diagnostic and immunotherapy techniques for WDEIA.

Varicose veins (VV) in legs are commonly observed in the general global population. However, the prevalence of and risk factors for VV in Japan are not clear. This study aimed at clarifying the risk factors for VV in traditional rural areas of Shimane prefecture. Subjects (113 men and 205 women aged ≥45 years) were recruited from health examinations in those areas in 2012. VV were defined as a reflux of blood in the great and/or small saphenous vein and incompetent perforating veins detected by ultrasonography. Risk factors for VV were analyzed using logistic regression models that included various parameters. We also investigated the possible interaction between standing at work and overweight and calculated the synergistic index. VV were found in 20.1% of the subjects (12.4% of men and 24.4% of women). The previously known risk factors of prolonged upright standing posture during work, higher body mass index (BMI), female sex, and age were also significant factors for VV. There was a significant combined effect of overweight (BMI ≥25) and prolonged upright standing posture at work [adjusted odds ratio = 3.42; 95% confidence interval (CI), 1.07-10.89], although the synergistic effect was not significant [synergistic index = 1.3; 95% CI, 0.2-8.7]. The prevalence of VV in the traditional rural area of Shimane prefecture was comparable to that reported previously in European countries. Our results confirm that exposure to both prolonged standing at work and overweight exacerbate VV development. This finding is useful to develop strategies for VV prevention.

35歳，男性。初診半年前から特定の菓子パン摂食後の仕事中に蕁麻疹が生じるようになった。約1ヵ月前には，血圧低下，呼吸困難などのアナフィラキシー症状を呈した。小麦とグルテンのプリックテストは共に陽性であったが，IgE-RASTは陰性を示した。患者血清を用いたIgE免疫ブロットでω-5グリアジン特異IgEが陽性であり，小麦依存性運動誘発アナフィラキシーと診断した。症状の誘発には，グルテン摂取に加えてアスピリン内服と運動の同時負荷が必要であり，かつ菓子パン以外の小麦食品では蕁麻疹をみないため，菓子パン内に含まれる少量のサリチル酸誘導体などの添加物が発症に関与している可能性が考えられた。

SummaryBackground Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a special form of food allergy typically induced by exercise after ingestion of wheat products. We identified wheat omega-5 gliadin and high molecular weight-glutenin subunit (HMW-glutenin) as major allergens for WDEIA and clarified that simultaneous detection of serum IgE binding to synthetic epitope peptides of these allergens identifies more than 90% of WDEIA patients. However, the short synthetic peptides are not suitable for CAP-fluorescent enzyme-immunoassay (CAP-FEIA), which is widely utilized for detecting allergen-specific IgE. Objective In this study, we constructed a CAP-FEIA with recombinant HMW-glutenin, and evaluated its usefulness in identifying the patients with WDEIA. Methods Recombinant HMW-glutenin was expressed as histidine-tag protein in E. coli and purified by histidine-tag affinity column. Wheat, gluten, recombinant omega-5 gliadin, epitope peptide of HMW-glutenin, native and recombinant HMW-glutenin specific IgE in the sera from 48 patients with WDEIA, 16 patients with atopic dermatitis (AD) who had no immediate allergic reaction after wheat ingestion and 12 healthy controls were determined by using CAP-FEIA method. Results In 16 AD patients without wheat allergy 12 of them (75%) had positive results for native HMW-glutenin test in contrast to epitope peptide of HMW-glutenin (12.5%) and recombinant HMW-glutenin test (12.5%). These results indicate the native HMW-glutenin test has low specificity. Sensitivity and specificity of the IgE test with recombinant HMW-glutenin were 16.7% and 92.9%. These are well compatible with results obtained by using epitope peptide of HMW-glutenin. However, sensitivity and specificity reached to 93.8% and 92.9%, when the test was combined to the test with recombinant omega-5 gliadin. Conclusions and Clinical Relevance We demonstrated that recombinant HMW-glutenin is best for CAP-FEIA system in point of stability and specificity and confirmed that detection of specific IgE against recombinant HMW-glutenin is useful for diagnosis of WDEIA when combined with the CAP-FEIA (recombinant omega-5 gliadin) test.

Currently, the detection of crude buckwheat extract-specific IgE by ImmunoCAP (f11) (Phadia AB, Uppsala, Sweden) is widely used to diagnose buckwheat allergy. However, the results of this test do not always correlate with the development of allergic symptoms. This study aimed to evaluate the diagnostic usefulness of specific IgE antibody titers for the major buckwheat allergens Fag e 1 and Fag e 2. Specific IgE antibodies were determined using the ImmunoCAP method for native Fag e 1 and Fag e 2, recombinant Fag e 1 and Fag e 2, and crude buckwheat extract (f11) in 10 buckwheat allergy patients, 14 atopic dermatitis patients, and 15 healthy subjects. All buckwheat allergy patients showed positive results for native Fag e 1- and Fag e 2-specific IgE tests and for ImmunoCAP (f11). In contrast, the rates of atopic dermatitis patients with positive results for native Fag e 1- and Fag e 2-specific IgE tests were 64.2% (9/14) and 57.1% (8/14), respectively. The sensitivities of the test using recombinant proteins were lower than those of the test using native proteins. The area under the curve (AUC) as determined by receiver operating characteristic (ROC) curve analysis was the largest for the native Fag e 2-specific IgE test (0.967), with a sensitivity of 90% and a specificity of 89.6% (cut-off: 2.74 kUa/L). Thus, the native Fag e 2-specific IgE antibody titer obtained using the ImmunoCAP method is more reliable than the buckwheat ImmunoCAP (f11) value for predicting buckwheat allergy.

Exercise or aspirin intake enhances symptoms by increasing blood gliadin levels in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). Misoprostol, a synthetic analogue of prostaglandin E1 (PGE1) compensates prostagrandins of which synthesis is inhibited by aspirin and protect the gastrointestinal mucosa. We projected to examine the effect of misoprostol in suppression the allergic symptom and elevation of blood gliadin levels in WDEIA induced by aspirin.Two patients with a history of recurrent anaphylaxis associated with wheat ingestion accompanied with exercise, positive specific IgE and/or skin test were enrolled in the provocation test. On the provocation test of WDEIA, wheat ingestion, exercise, aspirin intake were combined on various ways. During the test, the patients' symptom and serum gliadins levels were monitored.Although wheat with exercise did not induce any symptoms, addition of aspirin induced urticaria and elevation of blood gliadin levels in both cases. In case 1, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by exercise, wheat and aspirin intake. In case 2, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by wheat and aspirin intake.These findings suggest that a synthetic analogue of PGE1 may suppresses the absorption of the allergen levels and outbreak the allergic symptom induced by aspirin in the patients with WDEIA.

A 47 years-old woman suffering from baker's asthma for several years developed anaphylaxis when she was walking hard after taking wheat. On the provocation test, neither wheat alone nor exercise alone induced any symptoms. The combination of exercise, wheat and aspirin induced urticaria and marked elevation of blood gliadin levels. According to the high titer of omega-5 gliadin specific IgE in her serum and the result of challenge test, we diagnosed wheat-dependent exercise-induced anaphylaxis (WDEIA). By means of western blotting of soluble and insoluble wheat proteins, we detected several bands which were supposed to be beta-, gamma- and omega-5 gliadin by their relative molecular mass. Wheat gliadins might be causative allergen of both baker's asthma and WDEIA in our case.

Background: Gliadins have been implicated in immunoglobulin E (IgE)-mediated allergy to ingested wheat and ω-5-gliadin is known to represent a major allergen in wheat-dependent exercise-induced anaphylaxis. Less known is whether ω-5-gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to ω-5-gliadin (sIgE-ω-5-gliadin-ab) could be used as a marker for oral wheat challenge outcome in wheat-sensitized children. A secondary objective was to study whether the level of sIgE-ω-5-gliadin was related to symptom severity in children with a positive challenge test. Methods: Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE-ω-5-gliadin-ab was related to a physician’s diagnosis of wheat allergy and challenge symptoms. Results: The mean concentration of sIgE-ω-5-gliadin-ab was 7.25 kUA/l in patients with wheat allergy and 1.08 kUA/l in patients with no wheat allergy (P

Wheat ω-5 gliadin and a high m.w. glutenin subunit (HMW-glutenin) have been reported as major allergens in wheat-dependent exercise-induced anaphylaxis. A simultaneous detection of specific IgE to epitope sequences of both proteins is considered to be a reliable method for diagnosis of wheat-dependent exercise-induced anaphylaxis. However, the IgE-binding epitope of HMW-glutenin remains unknown. The aim of this study was to determine the IgE-binding epitopes of HMW-glutenin to establish a useful system of identifying patients with wheat-dependent exercise-induced anaphylaxis. For determination of IgE-binding epitopes of HMW-glutenin overlapping peptides were synthesized and reactivities of IgE Abs in the sera of patients to those peptides were analyzed. Three IgE-binding epitopes, QQPGQ, QQPGQGQQ, and QQSGQGQ, were identified within primary sequence of HMW-glutenin. Epitope peptides, which include IgE-binding sequences of ω-5 gliadin and a HMW-glutenin, were synthesized and peptide-specific IgE Abs were measured by CAP-System fluorescent enzyme immunoassay. Twenty-nine of 30 patients with wheat-dependent exercise-induced anaphylaxis had specific IgE Abs to these epitope peptides. None of the 25 sera from healthy subjects reacted to both epitope peptides. Twenty-five patients with atopic dermatitis who had specific IgE to wheat and/or gluten had very low or nonexistent levels of epitope peptide-specific IgE Abs. These results indicated that measurement of IgE levels specific to epitope peptides of ω-5 gliadin and HMW-glutenin is useful as an in vitro diagnostic method for the assessment of patients with wheat-dependent exercise-induced anaphylaxis.

BackgroundFood-dependent exercise-induced anaphylaxis (FDEIA) is a distinct form of common food allergy characteristically induced by a combination of causative food ingestion and physical exercise. Recent investigations have documented that aspirin consumption, in place of exercise, also induces allergic symptoms.Case SummaryA 63-year-old man began low dose aspirin therapy on September 2005. Since January 2006, he had repeated episodes of generalized urticaria and lost consciousness while he was exercising after eating wheat. He was strongly positive for ω-5 gliadin in a cap-system fluorescent enzyme immunoassay. Therefore, a diagnosis of wheat-dependent exercise-induced anaphylaxis was made.DiscussionPatients with aspirin-provoked FDEIA have been reported previously as taking ordinary doses of aspirin for reducing pain, inflammation and fever. However, in our patient, low dose aspirin therapy for reducing cardiovascular risk possibility induced FDEIA. Growing numbers of elderly people take low doses of aspirin for prevention of cerebral or myocardial infarction. Therefore, physicians should remember that aspirin consumption, even at low doses, is a risk factor for FDEIA.

Background: Challenge testing with wheat plus exercise and or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA. Methods: Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations―Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable―were given according to the results of wheat plus exercise and or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and or dietary management in Group II and III. Results: Positive results for wheat plus exercise and or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes. Conclusions: Our study revealed that serum gliadin monitoring during challenge testing is useful.