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BACKGROUND It has been reported that the risk of erectile dysfunction (ED) is significantly higher in patients with obstructive sleep apnea (OSA), compared with patients without OSA. However, there is limited evidence on whether surgical treatments in patients with OSA could decrease ED risk. OBJECTIVES To assess the impact of surgical treatments for OSA on the risk of ED by analysis of claims data from the Taiwan National Health Insurance Research Database between 1997 and 2012. MATERIAL AND METHODS We identified 20,675 male adults with newly diagnosed OSA during the study period; 16,040 patients ever received surgical treatments (treated cohort) and 4635 patients never received surgical treatments (untreated cohort). According to 3:1 propensity score matching, we analyzed 8337 patients in the treated cohort and 2779 controls in the untreated cohort. We estimated the incidence rates (IRs) and hazard ratios (HRs) of incident ED in both cohorts through the end of 2012. RESULTS In a total study follow-up of 64,916 person-years, 396 (3.6%) patients developed impotence. The IRs of ED for the treated and untreated cohorts, respectively, were 55.8 (95% confidence interval [CI], 55.6-55.9) and 76.1 (95% CI, 76.0-76.3) per 1000 person-years. Multivariate Cox proportional hazard analysis showed that surgical treatments for OSA patients were associated with a lower risk for ED (adjusted HR, 0.79; 95% CI, 0.64-0.98). Multivariate stratified analysis further verified that significant risk reduction of ED was present in OSA patients without hypertension, diabetes, hyperlipidemia, hyperuricemia, obesity, chronic kidney disease, and chronic liver disease. CONCLUSIONS We found that OSA patients who received surgical treatments were associated with a lower risk for developing ED by 21%.

Background: Alzheimer’s disease (AD) leads to progressive neuronal loss and cognitive and behavioral decline in the aging population. Matrix metalloproteinases (MMPs) and associated tissue inhibitors of metalloproteinases (TIMPs) are involved in remodeling the extracellular matrix. Amyloid beta-42 interrupts the integrity of the neurovascular unit and induces a toxic reaction affecting neurons. Objective: This study investigated the relationships among genetic variants of the MMP-2, MMP-9, TIMP-1, and TIMP-2 genes and AD. Methods: Two hundred and thirteen probable AD patients and 315 control participants of the Taiwan population were recruited for primary investigations, and we used the data of 763 participants from the Taiwan Biobank (TWB), as controls, for validation. Multivariable logistic regression was performed with adjustments for age, sex, hypertension, diabetes mellitus (DM), and alcohol consumption. The associations between the genotypes and allele frequencies and the SNP-associated AD hereditary models were analyzed using the SNPassoc package for R. We performed a permutation test with 1,000 replicates for the empirical estimates. Results: A total of 213 probable AD patients and 315 control participants were recruited. The frequency of the A alleles in rs7503726 (G > A) in TIMP-2 was lower in the AD patients (p < 0.01). The frequencies of the TIMP-2 rs7503726 G/A and A/A genotypes were also significantly lower in the AD patients (p = 0.02) than in the controls and TWB. The TIMP-2 rs7503726 AA genotype was associated with a protective effect of AD in additive and recessive hereditary models (OR = 0.54, 95% CI: 0.32 - 0.92, p = 0.02; OR = 0.68, 95% CI: 0.50 - 0.92, p = 0.01, respectively). Conclusion: The TIMP-2 rs7503726 AA genotype was inversely correlated with AD susceptibility, and the presence of minor alleles of rs7503726 (A allele) have protective effects against AD.

Hepatitis B virus (HBV) infection has been proposed to play a role in the development of Sjögren's syndrome. However, to date, there are no reports on the risk of SS in HBV-infected patients following nucleos(t)ide analogue therapy. Due to Taiwan has higher prevalence of HBV infection and therapy was well recorded in the Taiwan's single-payer national health insurance database, we hypothesized that a long-term retrospective analysis of the risk of Sjögren's syndrome in HBV-infected patients following nucleotide therapy will increase our understanding of Sjögren's syndrome development following HBV infection. We identified 26,147 adults diagnosed with HBV infection between 1997 and 2012 in claims data. Finally, a total of 3268 HBV-infected patients who ever received nucleotide therapy (treated cohort) were frequency-matched on age and sex at 1:4 ratios to select a control group of 13,072 counterparts without therapy (untreated cohort). To identify Sjögren's syndrome risk, competing risk analysis adjusted for all covariates was performed. The risk was significantly lower in the treated cohort (15-year cumulative incidence, 2.4%; 95% confidence interval [CI], 1.4%-3.7%) than in the untreated cohort (7.1%; 95% CI, 2.5%-15.2%) (p = .015), and the adjusted HR was 0.6 (95% CI, 0.41-0.88; p = .009). Multivariable stratified analysis further verified the consistent associations between nucleoside therapy and risk reduction of Sjögren's syndrome across all strata. Our finding suggests that HBV infection treated with nucleotides is associated with lower risk of Sjögren's syndrome, implying a potential role of HBV infection in the development of Sjögren's syndrome.

Background Oxidative stress could participate in the pathogenesis of Parkinson's disease (PD). However, the role of genetic variation of superoxide dismutase 2 (SOD2), an important regulator against oxidative stress, in PD remains to be elucidated. Methods We screened SOD2 gene variation by sequencing cDNA from 72 patients with early onset PD. A cohort of PD (n = 609) and ethnically matched controls (n = 681) were further examined for the identified sequence variant by PCR and NaeI restriction analysis. Results Only a reported c.47T>C polymorphism (rs4880, SOD2 p.V16A) was found by cDNA sequencing. Case-control study of c.47T>C revealed that genotype and allele frequencies were in Hardy–Weinberg equilibrium in both patients and healthy controls. In a recessive model, those with CC genotype had a 2.61-fold increased risk of PD (95% CI: 1.08–6.30, P = 0.03) compared to subjects with TT and TC genotypes. Significant association between CC genotype and PD in non-smokers was also observed after stratification according to the history of smoking (3.54-fold increased risk of PD, 95% CI: 1.17–10.72, P = 0.02). Meta-analysis by combining studies of Chinese in China, Singapore, and Taiwan (total 2302 cases and 2029 controls) consistently showed CC genotype with increased risk of PD (OR = 1.77, 95% CI: 1.15–2.71, P = 0.01). Conclusion Our findings demonstrate that SOD2 p.V16A may play a role in the susceptibility of PD in Han Chinese.

Objective The Clinical Dementia Rating (CDR) Scale comprising global score (CDR-GS) and sum of boxes scores (CDR-SB) is commonly used in staging cognitive impairment; however, its diagnostic accuracy is not well clarified. The meta-analysis aimed to investigate the diagnostic accuracy of the CDR for mild cognitive impairment (MCI) and dementia in older populations. Methods Studies examining the diagnostic accuracy of the CDR for MCI or dementia against reference standards were included from seven electronic databases. The bivariate analysis with a random-effects model was adopted to calculate the pooled sensitivity and specificity of the CDR for MCI and dementia. Results Fifteen studies investigating the diagnostic accuracy of the CDR-GS (n = 13) or CDR-SB (n = 5) for MCI or dementia were included. The pooled sensitivity and specificity of the CDR-GS for MCI were 93% and 97%, respectively. With respect to dementia, the CDR-GS had superior pooled specificity compared to the CDR-SB (99% vs. 94%), while similar sensitivities were found between the CDR-GS and CDR-SB (both 87%). Significant moderators of an old age, a high educational level, a high prevalence of MCI or dementia, being in a developing country, and a lack of informants' observations may affect the estimation of the sensitivity or specificity of the CDR. Conclusions Evidence supports the CDR being useful for detecting MCI and dementia; applying the CDR for staging cognitive impairment in at risk populations should be considered. Furthermore, including objective observations from relevant informants or proxies to increase the accuracy of the CDR for dementia is suggested.

Background and objectives Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). Methods Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. Results In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). Conclusions There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.

Objectives To examine the association between service volume and guideline adherence via multiyear observations. Study design Repeated cross-sectional study. Methods This study employed nationwide claims data from Taiwan's National Health Insurance scheme and identified patients with newly diagnosed type 2 diabetes from 2001, 2005, and 2009; a new prescription guideline for diabetes care was introduced in 2006. Physician service volume was measured by the number of total outpatients with diabetes. The outcome variable indicated whether a patient was receiving metformin, the guideline-recommended antihyperglycemic agent, at the index date. Results Patients visiting physicians who had high or medium volumes of patients with diabetes were more likely to receive metformin than patients visiting physicians who had low volumes; the odds ratios (ORs) were 2.48 (95% CI, 2.03-3.04) and 1.76 (95% CI, 1.45-2.13), respectively. Patients with newly diagnosed diabetes in 2009 and 2005 were more likely to receive metformin than their counterparts in 2001, with ORs of 12.00 (95% CI, 11.19-12.86) and 2.44 (95% CI, 2.30-2.59), respectively. We also found that patients who visited younger physicians, physicians with fewer practice years, physicians practicing in large-scale hospitals, or physicians practicing in urban areas were more likely to receive metformin than their counterparts. Conclusions In the process of implementing a new practice guideline for treating patients with diabetes, physicians with higher patient volumes are more likely to adhere to the guideline recommendation.

Emerging evidence highlights the role of non-coding small RNAs in host-influenza interaction. We have identified a Y RNA-derived small RNA, miR-1975, which is upregulated upon influenza A virus infection in A549 cells. The aim of this study is to investigate whether miR-1975 serves as an indicator of clinical severity upon influenza infection. We investigate the abundance of miR-1975 in sera from clinical patients and its correlation with hypoxemia status. We quantified its amounts in sera from influenza virus-infected patients and healthy volunteers by means of stem-loop RT-PCR. Median values of miR-1975 were significantly higher in influenza virus-infected patients, especially in hypoxemic patients. miR-1975 levels at the acute stage of the disease were highly correlated with the fraction of inspired oxygen used by the patients and total ventilator days. Receiver operator characteristic curve analysis revealed that miR-1975 levels in combination with days of fever before presenting to hospital had significant predictive value for hypoxemia and respiratory failure for patients infected with influenza virus. Our results reveal that circulating miR-1975 has great potential to serve as a biomarker for predicting prognosis in patients infected with influenza virus.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of lung cancer. Both small-cell lung cancer (SCLC) and LELC often manifest as a centrally located tumor with lymphadenopathy. This retrospective study investigated and compared the initial computed tomography (CT) features and subsequent survival outcomes of LELC and SCLC. Methods: A total of 50 patients with a confirmed diagnosis of LELC were enrolled and matched at a ratio of 1:1 with patients with SCLC according to the tumor stage. Utilizing a consensus approach, two radiologists reviewed pretreatment CT images. Survival outcomes were analyzed. Results: Well-defined tumors were significantly more common in the LELC group (LELC: 42% vs SCLC: 24%, p = 0.005). Based on the comparisons of the primary tumor with the muscles, LELC tumors exhibited a significantly higher percentage of attenuation on contrast-enhanced CT scans (21.6% ± 29% vs −14.2% ± 37%, p < 0.001). The prevalence of vascular or bronchial encasement (18% vs 40%, p = 0.028), background emphysematous changes (10% vs 60%, p < 0.001), and tumors located in upper lobes (18% vs 64%, p < 0.001) was significantly lower in the LELC group. Female gender (70% vs 12%, p < 0.001), younger age (57.6 ± 12.0 years vs 68.0 ± 11.0 years, p < 0.001), and without a history of smoking (16% vs 88%, p < 0.001) were factors more commonly found in the LELC group. The patients with LELC had a better prognosis with significantly longer median survival than did the patients with SCLC (23.4 months vs 17.3 months, p = 0.01). Conclusion: Because SCLC demonstrated a more aggressive disease progression, differentiating LELC from SCLC is crucial. In Epstein–Barr virus-endemic areas, the diagnosis of LELC should be considered when approaching a patient with the above-mentioned CT and clinical features.

BACKGROUND Anesthesia and surgery may increase the risk of dementia in the elderly, but the higher prevalence of dementia in women and other evidence suggest that dementia risk increases in younger women undergoing hysterectomy. In this study, we assessed the risk of dementia after hysterectomy. METHODS Hysterectomies registered in the National Health Insurance Research Database from 2000 to 2013 were evaluated using a retrospective generational research method. Multivariate Cox regression analysis was used to assess the effect of age at surgery, anesthesia method, and surgery type on the hazard ratio (HR) for the development of dementia. RESULTS Among 280 308 patients who underwent hysterectomy, 4753 (1.7%) developed dementia. Age at surgery and anesthesia method were associated with the occurrence of dementia, independent of surgery type. Among patients 30-49 years of age, general anesthesia (GA) was associated with a higher risk of dementia than spinal anesthesia (SA). The HR for GA was 2.678 (95% confidence interval [CI] = 1.269-5.650) and the risk of dementia increased by 7.4% for every 1-year increase in age (HR = 1.074; 95% CI = 1.048-1.101). In patients >50 years of age, the HR for GA was 1.206 (95% CI = 1.057-1.376), and the risk of dementia increased by 13.0% for every 1-year increase in age (HR = 1.130; 95% CI = 1.126-1.134). CONCLUSION The risk of dementia in women who underwent hysterectomy was significantly affected by older age at surgery, and the risk might not increase linearly with age, but show instead an S-curve with exponential increase at about 50 years of age. Although less significant, GA was associated with higher risk than SA, and the effect of the anesthesia method was greater in patients

Autologous pancreatic islet transplantation is an established therapy for patients with chronic pancreatitis. However, the long-term transplant outcomes are modest. Identifying indicators of graft function will aid the preservation of transplanted islets and glycemic control. To this end, we analyzed beta cell prohormone peptide levels in a retrospective cohort of total pancreatectomy autologous islet transplant patients (n=28). Proinsulin-to-C-peptide (PI/C) and proIAPP-to-total IAPP (proIAPP/IAPP) ratios measured at 3 months post-transplant were significantly higher in patients who remained insulin dependent at 1 year follow-up. In a mouse model of human islet transplantation, recipient mice that later became hyperglycemic displayed significantly higher PI/C ratios than mice that remained normoglycemic. Histological analysis of islet grafts showed reduced insulin- and proinsulin-positive area, but elevated glucagon-positive area in grafts that experienced greater secretory demand. Increased prohormone convertase 1/3 was detected in glucagon-positive cells, and glucagon-like peptide 1 (GLP-1) area was elevated in grafts from mice that displayed hyperglycemia or elevated plasma PI/C ratios, demonstrating intra-islet incretin production in metabolically challenged human islet grafts. These data indicate that in failing grafts, alpha cell prohormone processing is likely altered, and incomplete beta cell prohormone processing may be an early indicator of insulin dependency.

Medication nonadherence is associated with an increased risk of complications in hypertensive patients. We investigated behavioral factors associated with medication nonadherence in hypertensive patients in southern Taiwan. Using questionnaires, we collected data regarding clinicodemographic characteristics and nonadherence behaviors from 238 hypertensive patients. We assessed the self-reported prevalence of specific behaviors of medication nonadherence and investigated factors associated with each behavior using multivariable logistic regression analysis. The most common behavior of medication nonadherence was forgetting to take medication (28.6%), followed by discontinuing medication (9.2%) and reducing the medication dose (8.8%). Age ≥ 65 years (adjusted odds ratio [aOR] = 0.32, 95% confidence interval [CI] = 0.15–0.69) and male sex (aOR = 2.61, CI = 1.31–5.19) were associated with forgetting to take medication. The presence of comorbidities (diabetes, kidney disease, or both) and insomnia (aOR = 3.97, 95% CI = 1.30–12.1) was associated with reducing the medication dose. The use of diet supplements was associated with discontinuing the medication (aOR = 4.82, 95% CI = 1.50–15.5). Compliance with a low oil/sugar/sodium diet was a protective factor against discontinuing medication (aOR = 0.14, 95% CI = 0.03–0.75). The most pervasive behavior associated with medication nonadherence among hypertensive patients was forgetting to take medication. Age &lt, 65 years, male sex, comorbidities, insomnia, noncompliance with diet, and the use of dietary supplements were specifically associated with medication nonadherence.

BACKGROUND Hepatitis C virus (HCV) infection is a documented risk factor for chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). However, to date there are no reports on the long-term hard endpoints (ESRD and death) of anti-HCV therapy [interferon-based therapy (IBT) or new direct-acting antivirals] in CKD patients. Direct-acting antivirals are not available in Taiwan’s single-payer national health insurance database currently released for research. Therefore, we hypothesized that a retrospective analysis of the long-term outcomes of IBT in CKD patients will serve as a proxy for direct-acting antivirals to increase our understanding of progression to ESRD following HCV infection. AIM To evaluate the long-term outcomes (ESRD and death) of anti-HCV therapy, especially IBT, in HCV-infected patients with stage 1-5 CKD. METHODS We analyzed 93894 Taiwanese adults diagnosed with CKD and without HBV infection. Of these, 4.9% were infected with HCV. Of the 4582 HCV-infected CKD patients, 482 (10.5%) received IBT (treated cohort). They were matched 1:4 with 1928 untreated HCV-infected CKD patients (untreated cohort) by propensity scores and year, which further matched 1:2 by propensity scores with 3856 CKD patients without HCV infection (uninfected cohort). All participants were followed until the occurrence of ESRD, death, or the end of 2012. The association between HCV infection, IBT use, and risks of ESRD and death was analyzed using competing risk analysis. RESULTS Taking the uninfected cohort as a reference, the adjusted hazard ratios for ESRD, after adjusting for competing mortality, were 0.34 (0.14-0.84, P = 0.019) and 1.28 (1.03-1.60, P = 0.029) in the treated and untreated cohorts, respectively. The treated cohort had a 29% (0.54-0.92, P = 0.011) decrease in mortality compared to the untreated cohort, in which the mortality was 31% (1.18-1.45, P < 0.001) higher than in the uninfected cohort. The reduced risks of ESRD (0.14, 0.03–0.58, P = 0.007) and death (0.57, 0.41-0.79, P = 0.001) were greatest in HCV-infected CKD patients who received at least 4 mo of IBT, which accounted for 74% of the treated cohort. CONCLUSION Adequate anti-HCV therapy in CKD patients improves long-term renal and patient survival.

In addition to airborne particulate matter (PM), exposure to spray paint PMs (SPPMs) may also be associated with pulmonary dysfunction. In this study, we employed human normal bronchial epithelial BEAS-2B cells to elucidate the association between pulmonary toxicity and different sizes of SPPMs (SPPM10-3.2, SPPM3.2-1 and SPPM1) under realistic environmental concentrations in a spray paint factory. Results indicated that all SPPMs (20–100μg/cm2) induced significant decreases in cell viability (> 70% compared to the control), except for low-dose SPPM10-3.2 (20 and 50μg/cm2). Almost all SPPMs (20μg/cm2 and 100μg/cm2) induced oxidative stress (2–4 times that of the control), which increased the production of proinflammatory cytokines (1.5–4.5 times that of the control) as well as increased α1-antitrypsin expression (3–4.5 times that of the control). Moreover, we found that almost all SPPMs induced pulmonary epithelial barrier dysfunction (0.77–0.11 times that of the control) through the depletion of zonula occludens proteins (0.8–0.65 times that of the control). In conclusion, smaller SPPMs induced more severe adverse pulmonary adverse effects. Exposure to SPPM1 was a potential major risk factor for pulmonary epithelial barrier dysfunction. Our evidence demonstrates that exposure to SPPMs, especially SPPM1, may increase the risk of pulmonary dysfunction.

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Vitamin D’s function in the development of gestational diabetes mellitus (GDM) is not consistent in the literature. We examined the association between maternal plasma 25(OH)D concentration and GDM risk. A national cross-sectional study (1497 pregnant women) was conducted between 2017 and 2019 across Taiwan. Blood samples were drawn at recruitment to assess 25(OH)D concentrations, including vitamin D deficiency (VDD) (&lt, 20 ng/mL), insufficiency (&lt, 32 ng/mL), and sufficiency (≥32 ng/mL). GDM was detected from 24 to 28 weeks of gestation with the results extracted from the antenatal visit records. The prevalence of GDM was 2.9%. Logistic model analysis showed that 25(OH)D concentrations were not significantly associated with the risk of GDM (adjusted odds ratio (AOR) = 0.97, p = 0.144). However, subjects with VDD had a significantly greater risk of GDM (AOR = 2.26, p = 0.041), but not in those with vitamin D insufficiency (AOR = 1.20, p = 0.655). Furthermore, cubic piecewise spline regression was used to explore the relationship between five-unit intervals of 25(OH)D and the predicted probability of GDM. As the proportion of GDM increased for low 25(OH)D concentrations, it decreased at moderate concentrations and increased again at higher concentrations. These findings revealed a nonlinear relationship between 25(OH)D and GDM risk. VDD would be risky for GDM occurrence.

Objective:The coexistence of underweight (UW) and overweight (OW)/obese (OB) at the population level is known to affect iron deficiency (ID) anaemia (IDA), but how the weight status affects erythropoiesis during pregnancy is less clear at a population scale. This study investigated associations between the pre-pregnancy BMI (pBMI) and erythropoiesis-related nutritional deficiencies.Design:Anthropometry, blood biochemistry and 24-h dietary recall data were collected during prenatal care visits. The weight status was defined based on the pBMI. Mild nutrition deficiency-related erythropoiesis was defined if individuals had an ID, folate depletion or a vitamin B12 deficiency.Setting:The Nationwide Nutrition and Health Survey in Taiwan (Pregnant NAHSIT 2017–2019).Participants:We included 1456 women aged 20 to 45 years with singleton pregnancies.Results:Among these pregnant women, 9·6 % were UW, and 29·2 % were either OW (15·8 %) or OB (13·4 %). A U-shaped association between the pBMI and IDA was observed, with decreased odds (OR; 95 % CI) for OW subjects (0·6; 95 % CI (0·4, 0·9)) but increased odds for UW (1·2; 95 % CI (0·8, 2·0)) and OB subjects (1·2; 95 % CI (0·8, 1·8)). The pBMI was positively correlated with the prevalence of a mild nutritional deficiency. Compared to normal weight, OB pregnant women had 3·4-fold (3·4; 95 % CI (1·4, 8·1)) higher odds for multiple mild nutritional deficiencies, while UW individuals had lowest odds (0·3; 95 % CI (0·1, 1·2)). A dietary analysis showed negative relationships of pBMI with energy, carbohydrates, protein, Fe and folate intakes, but positive relationship with fat intakes.Conclusion:The pre-pregnancy weight status can possibly serve as a good nutritional screening tool for preventing IDA during pregnancy.

Proinsulin (PI) is processed to mature insulin by prohormone convertases 1/3 (Pcsk1) and 2 (Pcsk2). In individuals with T1D and T2D, there is an increase in the circulating PI:insulin ratio. We hypothesized that β-cell Pcsk1 and Pcsk2 deletion would result in β-cell dysfunction, loss of insulin production, and marked hyperglycemia. Single Pcsk1flox/flox Ins1cre/+ (Pcsk1βKO), Pcsk2flox/flox Ins1cre/+ (Pcsk2βKO), and double Pcsk1flox/flox Pcsk2flox/flox Ins1cre/+ (DPCβKO) β-cell prohormone convertase knockout mice were generated (with respective Pcsk1+/+ Pcsk2+/+ Ins1cre/+ controls) and monitored until 30 weeks old. Pcsk2βKO mice displayed no glycemic phenotype, while Pcsk1βKO mice displayed mild hyperglycemia and impaired glucose tolerance by 26 weeks of age. DPCβKO mice displayed mild hyperglycemia (10.1±1.6 vs. 12.3±2.1 mM; p=0.006) and marked glucose intolerance by 10 weeks of age (AUC: 418±135 vs. 1485±360; p Our results suggest that complete loss of β-cell prohormone processing, including PI processing, can drive β-cell dysfunction and expansion, but only mild diabetes and glucose intolerance. Although Pcsk2 deletion in β cells does not impact glycemia or PI processing, it is required for normal proIAPP processing. In total, our data support the idea that altered β-cell prohormone processing does not impact obesity but can contribute to the pathogenesis of diabetes via β-cell dysfunction. Disclosure A. Taylor: None. Y. Chen: None. D. Pasula: None. D. S. Luciani: None. B. Verchere: Advisory Panel; Self; Integrated Nanotherapeutics Inc., Sirona Biochem, Stock/Shareholder; Self; Integrated Nanotherapeutics Inc. Funding Canadian Institutes of Health Research

Air pollution is a major worldwide concern, and exposure to particulate matter (PM) can increase the risks of pulmonary diseases. Normal human bronchial epithelial cells were applied to clarify the role of ultrafine PM (UFPM) in the pathogenesis of pulmonary toxic effects with realistic alveolar deposition doses. The UFPM used in this research originated from vehicular emissions and coal combustion. UFPM exposure of up to 72 h was found to induce significant time- and concentration-dependent decreases in cell viability. Exposure to UFPM increased reactive oxygen species (ROS) accumulation through heme oxygenase-1 (HO-1) inhibition and induced massive oxidative stress that increased the interleukin-8 (IL-8) expression. UFPM also reduced the pulmonary trans-epithelial electrical resistance through the depletion of zonula occludens (ZO) proteins. Finally, UFPM decreased the α1-antitrypsin (A1AT) expression, which implies high risk of chronic obstructive pulmonary disease (COPD). The evidence demonstrates that exposure to UFPM, even at very low concentrations, may affect the functions of the respiratory system.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are two major alcohol-metabolizing enzymes. Moderate alcohol intake is a protective modified factor in Alzheimer’s disease (AD) while heavy alcohol intake and abstinence increased dementia risk. The associations between Alzheimer’s disease and alcohol-metabolizing genes are uncertain. This study examined the association of AD with seven ADH/ALDH single-nucleotide polymorphisms (SNPs), ADH1C rs2241894, ADH1B rs1229984, ALDH1B1 rs2073478, ALDH2 rs886205, rs4767944, rs4648328, and rs671. We enrolled 157 AD and 168 age- and sex-matched control subjects in pilot study to examine the association of AD with ADH/ALDH SNPs. Reconstructed ALDH2 haplotypes were performed. We measured plasma level of ADH1C and checked the interaction effect of AD–rs2241894 genotype on plasma ADH1C level. In extension study, we further examined 339 AD and 2,504 healthy control from the Taiwan Biobank. In pilot study, we observed that ADH1C rs2241894 TT genotype was negatively associated with AD in a recessive genetic model (OR = 0.25, 95% CI 0.09–0.75, p < 0.0001) in women. A strong linkage disequilibrium was observed among the four examined SNPs of ALDH2. No haplotype was related to AD. The plasma ADH1C level in AD was higher than that in control. After adjusted by age, sex, hypertension, diabetes mellitus, and alcohol, we found a significant interaction effect of AD–rs2241894 genotype on plasma ADH1C level (p = 0.04). This interaction effect was attributable to the association between AD and plasma ADH1C level (β estimate = 366, 95% CI 92.7∼639.4, p = 0.009). The genetic distribution of ADH1C rs2241894 showed strong ethnic heterogeneity, in which the T allele was the minor allele accounting for 28.5% in our study and 23.6% in East Asians, while it was a major allele in Americans, Europeans, and the global populations. No association was discovered between AD and the five SNPs: rs2241894, rs1229984, rs2073478, rs886205, and rs671 in the extension study. In summary, this study revealed a suggestive association between ADH1C rs2241894 and female AD in the pilot study, but failed to confirm this finding in a population database. Further age-matched and large sample size case-control studies are needed before rs2241894 can be interpreted as a protective genetic factor of AD.

Background Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. Methods Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. Results Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

This study aimed to determine the real-world, long-term prognostic impacts, and adverse effects (AEs) of bevacizumab (BEV) in Asian patients with ovarian/tubal/peritoneal cancers. We retrospectively reviewed the medical records of consecutive patients with ovarian/tubal/peritoneal cancer on front-line chemotherapy with or without BEV (Cohort 1) and those who relapsed following chemotherapy and/or BEV (Cohort 2) between 2011 and 2018 in a tertiary medical centre. Patient characteristics, BEV dosages, clinical outcomes, and AEs were analyzed. Hazard ratios for disease progression and death were analyzed using a cox proportional regression model. Benefits of BEV used throughout triweekly, in terms of improved progression-free survival (PFS) and overall survival (OS), were observed at a dosage of 7.5–15 mg/kg among advanced-stage Cohort 1 patients. A progression-free interval of

Proinsulin (PI) is processed to mature insulin by prohormone convertases 1/3 (Pcsk1) and 2 (Pcsk2). In individuals with T1D and T2D, there is an increase in the circulating PI:insulin ratio. We hypothesized that beta-cell Pcsk1 deletion would result in beta-cell dysfunction and hyperglycemia. Male and female Pcsk1flox/flox Ins1cre/+ (Pcsk1beta-KO) and Pcsk1+/+ Ins1cre/+ (Pcsk1beta-WT) mice were fed either a chow or a high fat diet (HFD; 45% fat) and monitored until 30 weeks of age. Despite an approximately 150-fold increase in fasting plasma PI (p < 0.001) and only immature insulin granules detectable by electron microscopy, chow-fed Pcsk1beta-KO male mice had normal glucose tolerance early in life and only developed glucose intolerance by 26 weeks of age (AUC: 934±294 vs. 597±223; p = 0.008). Histological analysis showed that male Pcsk1beta-KO mice displayed a trend toward increased beta-cell area (1.3±0.6 vs. 0.8±0.4%; p = 0.08). The unexpectedly mild hyperglycemia in Pcsk1beta-KO mice is likely due to incomplete disruption of proinsulin processing, as mass spectrometry and western blot analysis of Pcsk1beta-KO islets confirmed markedly elevated proinsulin, but detectable mature insulin. In HFD-fed cohorts, 3/10 Pcsk1beta-KO male mice developed sustained fasting hyperglycemia (>16 mM) after 19 weeks of diet. Chow and HFD-fed female Pcsk1beta-KO mice displayed no differences in glycemia or body weight from Pcsk1beta-WT controls. Deletion of both Pcsk1 and Pcsk2 in beta cells (Pcsk1flox/flox Pcsk2flox/flox Ins1cre/+) resulted in undetectable mature insulin in islets (western blot), and impaired glucose tolerance at 10 weeks of age in both chow-fed male and female mice. Our results suggest that beta-cell Pcsk1 deficiency is not sufficient to drive diabetes development, but increases diabetes susceptibility in conditions of increased insulin secretory demand. Our data in mice support the idea that beta-cell prohormone processing errors likely contribute to pathogenesis of diabetes but not obesity. Disclosure A. Taylor: None. Y. Chen: None. B. Verchere: Advisory Panel; Self; Integrated Nanotherapeutics Inc., Sirona Biochem. Stock/Shareholder; Self; Integrated Nanotherapeutics Inc. Funding Canadian Institutes of Health Research (PJT153156)

This study aimed to assess the effects of fish oil plus all-trans retinoic acid (ATRA) on lipid metabolism and fat accumulation. Forty male C57BL/6J mice were divided into four groups; the FO, SO, FR, and SR groups were provided with fish oil, soybean oil, fish oil with ATRA, and soybean oil with ATRA, respectively. After 16 weeks, the SR and FR groups had significantly lower body weight than the SO and FO groups. Moreover, the FR group had the lowest reproductive white adipose tissue weight, liver triglyceride level, and acetyl-CoA carboxylase activity and the highest acyl-CoA oxidase and catalase activities among all groups. Additionally, fish oil alone also showed significantly improved serum and liver lipid profiles. ATRA in combination with fish oil or soybean oil both had significantly decreased reproductive white adipose tissue and increased expression of liver peroxisome proliferator-activated receptor δ and retinoic acid receptor α. ATRA may inhibit weight gain and fat accumulation, thus preventing obesity.

Background: Patients with polytrauma are expected to have a higher risk of mortality than the summation of expected mortality for their individual injuries. This study was designed to investigate the outcome of polytrauma patients, diagnosed by abbreviated injury scale (AIS) ≥ 3 for at least two body regions, at a level I trauma center. Methods: Detailed data of 694 polytrauma patients and 2104 non-polytrauma patients with an overall Injury Severity Score (ISS) ≥ 16 and hospitalized between January 1, 2009, and December 31, 2014 for treatment of all traumatic injuries, were retrieved from the Trauma Registry System. Two-sided Fisher exact or Pearson chi-square tests were used to compare categorical data. The unpaired Student t-test was used to analyze normally distributed continuous data, and the Mann–Whitney U-test was used to compare non-normally distributed data. Propensity-score matching in a 1:1 ratio was performed using NCSS software with logistic regression to evaluate the effect of polytrauma on in-hospital mortality. Results: There was no significant difference in short-term mortality between polytrauma and non-polytrauma patients, regardless of whether the comparison was made among the total patients (11.4% vs. 11.0%, respectively; p = 0.795) or among the selected propensity score-matched groups of patients following controlled covariates including sex, age, systolic blood pressure, co-morbidities, Glasgow Coma Scale scores, injury region based on AIS. Conclusions: Polytrauma defined by AIS ≥3 for at least two body regions failed to recognize a significant difference in short-term mortality among trauma patients. Keywords: Polytrauma, Abbreviated injury scale, Injury severity, Monotrauma, Multiple trauma, Mortality

White matter hyperintensities (WMHs) include periventricular WMH (pvWMH) and deep WMH. When hyperintensities in the basal ganglia or brainstem are included, the collective term is subcortical hyperintensities. Both WMH and medial temporal lobe atrophy (MTA) are risk factors for cognitive decline. This prospective study enrolled participants aged 50-85 years and followed their neuropsychological assessments annually for 2 years to explore the interactive effects of WMH and MTA on longitudinal clinical decline. Brain MRI was performed at the beginning of enrollment. Of the 200 participants, 57 were "normal" individuals, 40 had dysexecutive mild cognitive impairment, 53 had amnestic mild cognitive impairment, and 50 had Alzheimer's disease (AD). Overall, MTA significantly correlated with pvWMH (p=0.0004) but not with deep WMH, as defined by criteria using the Scheltens' Scale. Total Scheltens' score was specifically associated with the domain of semantic fluency (beta=-0.4, 95% CI=-0.7 to -0.2, p=0.002), which remained significant when adjusting for MTA (beta=-0.3, 95% CI=-0.5 to -0.1, p=0.017). The pvWMH was significantly higher in AD subjects than in normal control subjects (beta=0.3, 95% CI=0.1 to 0.4, p=0.001), especially the periventricular occipital caps (beta=0.2, 95% CI=0.1 to 0.3, p=0.0003). Cox proportional hazards model showed that the periventricular bands (PVB) predicted 1-year clinical decline (hazard ratio [HR]=5.3, 95% CI=1.8 to 15.7, p=0.002), which remained significant when further adjusting for MTA (HR=4.0, 95% CI=1.3 to 12.1, p=0.013). In summary, pvWMH, especially the occipital caps, was correlated with MTA and the AD subgroup. Assessment of semantic fluency may be useful for the clinical evaluation of the degree of subcortical hyperintensity burden. Visual rating of PVB could be an independent predictor for 1-year clinical decline.

Multiple myeloma (MM) is an uncommon malignancy that involves proliferation of atypical plasma cells in the bone marrow, generally diagnosed in the seventh decade of life.1 Initial clinical signs and symptoms associated with MM are variable but usually include bone pain, anemia, hypercalcemia, and renal insufficiency. It is estimated that approximately 10% to 15% of patients with MM have concomitant immunoglobulin amyloid light-chain (AL) amyloidosis2, 3; of those patients, 29% to 40% have mucocutaneous disease.4 Here, we report a case of isolated nodules on the bilateral oral commissures as an unusual presenting sign of systemic AL amyloidosis, uncovering a diagnosis of MM.

// Pao-Jen Kuo 1, * , Shao-Chun Wu 2, * , Peng-Chen Chien 1 , Shu-Shya Chang 1 , Cheng-Shyuan Rau 3 , Hsueh-Ling Tai 1 , Shu-Hui Peng 1 , Yi-Chun Lin 1 , Yi-Chun Chen 1 , Hsiao-Yun Hsieh 1 and Ching-Hua Hsieh 1, 4 1 Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 4 Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, Taiwan * These authors have contributed equally to this work Correspondence to: Ching-Hua Hsieh, email: m93chinghua@gmail.com Keywords: artificial neural network (ANN); free-flap reconstruction; head and neck cancer; logistic regression (LR); surgical site infection (SSI) Received: September 04, 2017 Accepted: February 03, 2018 Published: February 09, 2018 ABSTRACT Background : The aim of this study was to develop an effective surgical site infection (SSI) prediction model in patients receiving free-flap reconstruction after surgery for head and neck cancer using artificial neural network (ANN), and to compare its predictive power with that of conventional logistic regression (LR). Materials and methods : There were 1,836 patients with 1,854 free-flap reconstructions and 438 postoperative SSIs in the dataset for analysis. They were randomly assigned tin ratio of 7:3 into a training set and a test set. Based on comprehensive characteristics of patients and diseases in the absence or presence of operative data, prediction of SSI was performed at two time points (pre-operatively and post-operatively) with a feed-forward ANN and the LR models. In addition to the calculated accuracy, sensitivity, and specificity, the predictive performance of ANN and LR were assessed based on area under the curve (AUC) measures of receiver operator characteristic curves and Brier score. Results : ANN had a significantly higher AUC (0.892) of post-operative prediction and AUC (0.808) of pre-operative prediction than LR (both P

Cosmetic facial filler-related central retinal artery occlusion (CRAO) is a devastating complication of facial hyaluronic acid (HA) injection and can be managed by intra-arterial thrombolytic therapy (IATT). The authors report on a 20-year-old woman who developed unilateral CRAO due to facial HA injection and who, despite prompt IATT, lost vision. A review of the related literature found 14 other female patients who developed cosmetic facial filler-related CRAO and accepted IATT management. In no case was vision loss clinically improved. IATT is not an effective preventive treatment of dermal filler-associated CRAO. The authors suggest careful preprocedural patient selection to prevent this complication.

With technical development, artificial intelligence (AI) has been actively involving in the healthcare industry. Augmented reality (AR) is an interactive experience with the combination of virtual objects and a real-world environment, and the objects reside in the environment of the real world through computer-generated images for the purpose to enhance perceptual effects, which can be applied in the fields of medical education and clinical practice. Researchers have found that learning motives and interests may be raised by AR. At a medical center, the inter-specialty team from the Teaching Department and Rehabilitation Department jointly developed an AR Medical Education App, which involves 44 muscle strength and walking exercises, including 6 upper limb movements, 28 lower limb exercises, and 10 cardiorespiratory exercises. Various exercise packages can be designed by health caregivers based on patient’s needs in exercise. The Orthopedics Ward applied it in the respiration training for patients who underwent spinal surgery, preventing respiratory comorbidities. The improved postoperative pulmonary function has been found when compared with that before surgery, with statistical significance. Respiration, upper and lower limbs exercises were persistently performed in patients who underwent spinal surgery, which also has been incorporated in routine nursing care to add diverse options of patient education materials for nursing personnel. In the future, aspects that required further efforts include: expanded software equipment, simplified operation mode, increased user-friendly features for equipment, and expended plentifulness of contents.

Background Female patients present with unique physiological and behavioral characteristics compared to male patients. The aim of this study was to investigate and compare the injury patterns, injury characteristics, and mortality of male and female patients hospitalized for treatment of motorcycle accident-related trauma in a level I trauma center. Methods Retrospective analysis of motorcycle-related injuries from the Trauma Registry System was performed to identify and compare 4028 male and 2919 female patients hospitalized for treatment between January 1, 2009 and December 31, 2013. Results The female patients were younger, less often drunken, more often wore helmets, were transported by emergency medical services, and arrived at the emergency department between 7 a.m. and 5 p.m. compared to male patients. Analysis of Abbreviated Injury Scale scores revealed that female patients sustained significantly higher rates of injuries to the extremities, but lower rates of injuries to the head/neck, face, and thorax than male patients did. Female patients had a significant lower Injury Severity Score (ISS) and adjusted odds ratio of in-hospital mortality (AOR 0.83, 95% CI: 0.83–0.86) after adjustment by ISS. However, the logistic regression analysis of propensity score-matched patients with adjusted confounders including helmet-wearing status and alcohol intoxication revealed that the gender did not significantly influence mortality (OR 0.82, 95% CI 0.47–1.43; p = 0.475), implying the an associated risky behaviors may attribute to the difference of odds of mortality between the male and female patients. In addition, a significantly fewer female patients were admitted to the intensive care unit (ICU), and female patients had a significantly shorter hospital and ICU length of stay. Conclusion Female motorcycle riders have different injury characteristics, lower ISS and in-hospital mortality, and present with a bodily injury pattern that differs from that of male motorcycle riders. Level of evidence Epidemiologic study, level III.

Background: To investigate the injury pattern, mechanisms, severity, and mortality of the elderly hospitalized for treatment of trauma following motorcycle accidents. Methods: Motorcycle-related hospitalization of 994 elderly and 5078 adult patients from the 16,548 hospitalized patients registered in the Trauma Registry System between January 1, 2009 and December 31, 2013. Results: The motorcycle-related elderly trauma patients had higher injury severity, less favorable outcomes, higher proportion of patients admitted to the intensive care unit (ICU), prolonged hospital and ICU stays and higher mortality than those adult motorcycle riders. It also revealed that a significant percentage of elderly motorcycle riders do not wear a helmet. Compared to patients who had worn a helmet, patients who had not worn a helmet had a lower first Glasgow Coma Scale (GCS) score, and a greater percentage presented with unconscious status (GCS score ≤8), had sustained subdural hematoma, subarachnoid hemorrhage, cerebral contusion, severe injury (injury severity score 16–24 and ≥25), had longer hospital stay and higher mortality, and had required admission to the ICU. Conclusions: Elderly motorcycle riders tend to present with a higher injury severity, worse outcome, and a bodily injury pattern differing from that of adult motorcycle riders, indicating the need to emphasize use of protective equipment, especially helmets, to reduce their rate and severity of injury.

Context: Islet amyloid is a feature of β-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in β cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in β-cell prohormone processing. Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes. Design, Setting, and Patients: We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls. Results: The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 Conclusion: The β cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of β-cell stress and dysfunction.

Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening disease entity characterized by widespread vascular thromboses causing multiorgan failure in the setting of antiphospholipid antibody positivity.1 CAPS is the most severe subset of antiphospholipid syndrome (APS), an autoimmune clotting disorder in which the body attacks its own phospholipids. CAPS can present with a variety of pseudovasculitic skin findings. We report on a CAPS patient with tumid lupus erythematosus (LE)-like lesions.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcohol-metabolizing enzymes. While alcohol use is associated with spontaneously deep intracerebral haemorrhage (SDICH), particularly in males, the activities and genetic variants of ADH and ALDH may affect SDICH development. This case-control study was conducted to identify the interaction of alcohol use and SDICH with five single-nucleotide polymorphisms (SNPs): ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs671, ALDH2 rs886205, and ALDH2 rs4648328. We enrolled 208 patients with SDICH and 244 healthy controls in a Taiwanese population. ALDH2 rs671 was significantly associated with SDICH in the dominant (P P = 0.007). ALDH2 rs4648328 was borderline significantly associated with SDICH in the recessive (P = 0.024) or additive models (P = 0.030). In alcohol-using patients, the ALDH2 rs671 GG genotype was associated with SDICH risk compared to the GA+AA genotype (P = 0.010). ADH1B rs1229984, ADH1C rs2241894, and ALDH2 rs886205 did not demonstrate association with SDICH. Thus, the ALDH2 rs671 GG genotype is a risk factor for SDICH. Because the genetic distributions of ALDH2 rs671 exhibited strong ethnic heterogeneity, further studies in different populations are needed to validate these findings.

Iron deficiency (ID) and iron deficiency anemia (IDA) typically occur in developing countries. Notably, ID and IDA can affect an infant&rsquo, s emotion, cognition, and development. Breast milk is considered the best food for infants. However, recent studies have indicated that breastfeeding for more than six months increases the risk of ID. This study investigated the prevalence of ID and IDA, as well as the association between feeding type and iron nutritional status in northern Taiwan. A cross-sectional study was conducted on infants who returned to the well-baby clinic for routine examination from October 2012 to January 2014. Overall, 509 infants aged 1&ndash, 12 months completed the iron nutritional status analysis, anthropometric measurement, and dietary intake assessment, including milk and complementary foods. The results revealed that 49 (10%) and 21 (4%) infants in their first year of life had ID and IDA, respectively, based on the World Health Organization criteria. Breastfed infants had a higher prevalence rate of ID and IDA than mixed-fed and formula-fed infants (p &lt, 0.001). Regarding biomarkers of iron status, plasma hemoglobin (Hb), ferritin, and transferrin saturation (%) levels were significantly lower in ID and IDA groups. The prevalence of ID and IDA were 3.7% and 2.7%, respectively, in infants under six months of age, but increased to 20.4% and 6.6%, respectively, in infants above six months of age. The healthy group had a higher total iron intake than ID and IDA groups, mainly derived from infant formula. The total dietary iron intake was positively correlated with infants&rsquo, Hb levels. Compared with formula-fed infants, the logistic regression revealed that the odds ratio for ID was 2.157 (95% confidence interval [CI]: 1.369&ndash, 3.399) and that for IDA was 4.196 (95% CI: 1.780&ndash, 9.887) among breastfed infants (p &lt, 0.001) after adjusted for all confounding factors (including gestational week, birthweight, sex, body weight percentile, body length percentile, age of infants, mothers&rsquo, BMI, gestational weight gain, education level, and hemoglobin level before delivery). In conclusion, our results determined that breastfeeding was associated with an increased the prevalence of ID and/or IDA, especially in infants above six months. This suggests that mothers who prolonged breastfeed after six months could provide high-quality iron-rich foods to reduce the prevalence of ID and IDA.

Cholinergic neurotransmission regulates the immune response and inhibits cytokine release after stroke. The changes in the level/activity of blood cholinesterase (ChE) in patients with post-stroke dementia (PSD) are less known. This study aimed to examine post-stroke plasma acetylcholinesterase (AChE) and butylcholinesterase (BChE) and determine whether they are biomarkers for PSD. Thirty patients with PSD, 87 post-stroke patients without dementia (PSNoD), and 117 age- and gender-matched healthy controls were recruited. Missense genetic variants AChE rs1799806 and BChE rs1803274 were genotyped. The plasma AChE level did not differ between the PSD and PSNoD groups. However, BChE levels were significantly lower in the PSD than in the PSNoD group (3300.66 &plusmn, 515.35 vs 3855.74 &plusmn, 677.60 ng/mL, respectively, p = 0.0033). The activities of total ChE, BChE, and AChE were all lower in the PSD group (19,563.33 &plusmn, 4366.03, 7650.17 &plusmn, 1912.29, 11,913.17 &plusmn, 2992.42 mU/mL, respectively) than in the PSNoD group (23,579.08 &plusmn, 5251.55, 9077.72 &plusmn, 1727.28, and 14,501.36 &plusmn, 4197.17 mU/mL, respectively). When further adjusting for age and sex, significance remained in BChE level and activity and in total ChE activity. BChE rs1803274 was associated with reduced BChE activity, while AChE rs1799806 did not influence AChE activity. The level and activity of BChE, but not of AChE, were decreased in PSD patients and may therefore aid in PSD diagnosis.

Background: CSF1/CSF1R neuroinflammatory signaling is emerging as an important pathway involved in the pathogenesis of Parkinson&rsquo, s disease (PD). However, the genetic associations between CSF1/CSF1R and PD have not yet been explored. Methods: We investigated the effects of two functional genetic variants, including CSF1 rs1058885 and CSF1R rs10079250 in a cohort including 502 Taiwanese patients with PD and 511 age- and gender-matched healthy controls. Results: The CSF1 rs1058885 TT genotype was less frequent in PD patients compared with control subjects (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.43&ndash, 0.92, p = 0.015). The PD patients also had a lower frequency of the CSF1 rs1058885 T allele compared with the control subjects (OR = 0.80, 95% CI: 0.67&ndash, 0.96, p = 0.014). No statistically significant differences in allelic and genotypic frequencies of CSF1R rs10079250 between the PD and control subjects were found, even after stratification by age at onset and gender. Conclusion: This study reports a genetic association between CSF1 and PD for the first time.

Heart rate variability (HRV) is an objective measure of emotional regulation. This study aimed to estimate the accuracy with which an artificial neural network (ANN) algorithm could classify emotions using HRV data that were obtained using wristband heart rate monitors. Four emotions were evoked during gameplay: pleasure, happiness, fear, and anger. Seven normalized HRV features (i.e., 3 time-domain features, 3 frequency-domain features, and heart rate), which yielded 29,727 segments during gameplay, were collected and analyzed first by statistics and then classified by the trained ANN model. General linear model adjusted for individual differences in HRV showed that all HRV features significantly differed across emotions, despite disparities in their magnitudes and associations. When compared to neutral status (i.e., no emotion evoked), the mean of R-R interval was significantly higher for pleasure and fear but lower for happiness and anger. In addition, pleasure evidenced the HRV features that suggested a superior parasympathetic to sympathetic activation. Happiness was associated with a prominent sympathetic activation. These statistical findings suggest that HRV features significantly differ across emotions evoked by gameplay. When further utilizing ANN-based emotion classification, the accuracy rates for prediction were above 75.0% across the 4 emotions with accuracy rates for classification of paired emotions ranging from 82.0% to 93.4%. For classifying emotion in an individual person, the trained ANN model utilizing HRV features yielded a high accuracy rate in our study. ANN is a time-efficient and accurate means to classify emotions using HRV data obtained from wristband heart rate monitors. Thus, this integrated platform can help monitor and quantify human emotions and physiological biometrics.

AIMS/HYPOTHESIS: Peptide hormones are first synthesised as larger, inactive precursors that are converted to their active forms by endopeptidase cleavage and post-translational modifications, such as amidation. Recent, large-scale genome-wide studies have suggested that two coding variants of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), are associated with impaired insulin secretion and increased type 2 diabetes risk. We aimed to elucidate the role of PAM in modulating beta cell peptide amidation, beta cell function and the development of diabetes. METHODS: PAM transcript and protein levels were analysed in mouse islets following induction of endoplasmic reticulum (ER) or cytokine stress, and PAM expression patterns were examined in human islets. To study whether haploinsufficiency of PAM accelerates the development of diabetes, Pam(+/−) and Pam(+/+) mice were fed a low-fat diet (LFD) or high-fat diet (HFD) and glucose homeostasis was assessed. Since aggregates of the PAM substrate human islet amyloid polypeptide (hIAPP) lead to islet inflammation and beta cell failure, we also investigated whether PAM haploinsufficiency accelerated hIAPP-induced diabetes and islet amyloid formation in Pam(+/−) and Pam(+/+) mice with beta cell expression of hIAPP. RESULTS: Immunostaining revealed high expression of PAM in alpha, beta and delta cells in human pancreatic islets. Pam mRNA and PAM protein expression were reduced in mouse islets following administration of an HFD, and in isolated islets following induction of ER stress with thapsigargin, or cytokine stress with IL-1β, IFN-γ and TFN-α. Despite Pam(+/−) only having 50% PAM expression and enzyme activity as compared with Pam(+/+) mice, glucose tolerance and body mass composition were comparable in the two models. After 24 weeks of HFD, both Pam(+/−) and Pam(+/+) mice had insulin resistance and impaired glucose tolerance, but no differences in glucose tolerance, insulin sensitivity or plasma insulin levels were observed in PAM haploinsufficient mice. Islet amyloid formation and beta cell function were also similar in Pam(+/−) and Pam(+/+) mice with beta cell expression of hIAPP. CONCLUSIONS/INTERPRETATION: Haploinsufficiency of PAM in mice does not accelerate the development of diet-induced obesity or hIAPP transgene-induced diabetes.

Stroke is an important risk factor for dementia. Epidemiological studies have indicated a high incidence of dementia in stroke patients. There is currently no effective biomarker for the diagnosis of post-stroke dementia (PSD). D-amino acid oxidase (DAO) is a flavin-dependent enzyme widely distributed in the central nervous system. DAO oxidizes D-amino acids, a process which generates neurotoxic hydrogen peroxide and leads to neurodegeneration. This study aimed to examine post-stroke plasma DAO levels as a biomarker for PSD. In total, 53 patients with PSD, 20 post-stroke patients without dementia (PSNoD), and 71 age- and gender-matched normal controls were recruited. Cognitive function was evaluated at more than 30 days post-stroke. Plasma DAO was measured using the enzyme-linked immunosorbent assay. White matter hyperintensity (WMH), a neuroimaging biomarker of cerebral small vessel diseases, was determined by magnetic resonance imaging. We found that plasma DAO levels were independently higher in PSD subjects than in PSNoD subjects or the controls and were correlated with the WMH load in stroke patients. Using an area under the curve (AUC)/receiver operating characteristic analysis, plasma DAO levels were significantly reliable for the diagnosis of PSD. The sensitivity and specificity of the optimal cut-off value of 321 ng/ml of plasma DAO for the diagnosis of PSD were 75 and 88.7%, respectively. In conclusion, our data support that plasma DAO levels were increased in PSD patients and correlated with brain WMH, independent of age, gender, hypertension, and renal function. Plasma DAO levels may therefore aid in PSD diagnosis.

Variations at the six nucleotides −3279 (T > G), −53 (A[TA]6TAA > A[TA]7TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP‐glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P

Background: After spinal surgery, patients often have changes in respiratory system due to general anesthesia. Preoperative respiratory rehabilitation and respiratory muscle training are found to be effective in reducing the postoperative pulmonary complications.Aim: Comparing the differences in the effects of postoperative lung expansion in patients with spinal surgery by using the conventional paper-based and the application of augmented reality (AR) health education methods, and understanding the acceptance of the use of AR by clinical nursing staff.Subject and methods: The quasi experiment was adopted; the control group was paper-based conventional health education and the experimental group was AR health education. The Trifflow breathing exercise was taught one day before operation. The frequency of exercise was 5-10 minutes each time and four times a day. The exercise was started from the day before operation and was continued until being discharged from the hospital. The pulmonary capacities were measured one day before the operation and on the day of leaving the hospital. Twenty people were recruited in both groups. There were 20 nursing staff participated in this study in total. The acceptance level of using AR was surveyed by using self-administered structured questionnaire.Result: In the experimental group, females were accounted for 65%, 55% of them were under 64 years old, and 30% of them with primary education level; in the control group, 85% of them were females, 70% of them were over 65 years old, and 30% with primary education level. The vital capacities measured at the time of discharge comparing with that before the operation were increased in both group, which reached a statistical difference (p=0.001). However, there was no significantly statistical difference between different groups. In terms of AR recognition by nursing staff: 75.0% thought that “the current health education tools are not enough”, 90% agreed that “acceptance of AR by patient and family”, 75% agreed that “the AR used in this health education process is convenient”, “the use of AR in this health education process is interactive”, and “AR health education makes the whole health education process more interesting”. Seventy percent agreed that “I have enough relevant resources to use AR health education”.Conclusion: Both traditional and AR health education models can improve the pulmonary function of patients, and there were significantly statistical differences. However, nursing staff felt that the current health education tools were not enough and thought that AR was interactive, interesting and convenient.Recommendation: The AR medical education has the advantages of interactive games and instant feedback. It can be utilized in clinical services to provide nurses with different models of health education.

Background/PurposeParkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Although idiopathic PD accounts for most of the cases, several genetic mutations have been found to cause PD. Mutations in the eukaryotic translation initiation factor 4-γ, 1 (EIF4G1) gene have been identified since 2011, which were reported to be associated with PD among Caucasians in subsequent research. However, this observation was not consistent. The contribution to other ethnic groups remains limited, with < 1% of sporadic cases. We conducted a case–control study to analyze if EIF4G1 is a risk factor for PD patients in Taiwan.MethodsThere were 595 PD patients and 600 controls without neurological diseases enrolled in this study. Four reported mutations—A502V (c.1505C>T), G686C (c.2056 G>T), R1197W (c.3589C>T), and R1205H (c.3614G>A)—were analyzed.ResultsThere were no mutations found in either PD patients or controls.ConclusionThis study indicates that the EIF4G1 mutation is rare in Taiwan, which is consistent with other reports from Asia. Ethnicity could have a great influence on EIF4G1 in PD. Further large scale studies are warranted to evaluate the association of PD and EIF4G1 gene.

Hypotony maculopathy is a sight-threatening complication after trabeculectomy. We report on a 34-year-old man with juvenile open-angle glaucoma and high myopia, who developed hypotony maculopathy 14 years after trabeculectomy without bleb leak. This represents the longest known period from trabeculectomy to the development of hypotony maculopathy without bleb leak. The possible mechanisms for the development of late-onset hypotony maculopathy in the highly myopic patient are progressive scleral thinning, reduced scleral rigidity, and scleral morphologic change with aging. These changes might weaken the biomechanical properties of sclera and then contribute to the collapse of the scleral wall during hypotony. This case serves as a reminder that hypotony maculopathy can happen up to 14 years after tabeculectomy even without bleb leak and hypotony should be avoided after trabeculectomy in highly myopic patients with juvenile open-angle glaucoma.

The triggers for the transition of gait from walking to running during increasing speed locomotion have been attributed to an energy conservation strategy or a relief of excessive muscle activation. Walking beyond the preferred transition speed (PTS) has been proposed as an exercise protocol for boosting energy consumption. However, the biomechanical factors involved while this protocol is used have not been investigated. Thus, this study investigated the difference between walking and running below, during, and beyond the PTS from a biomechanical perspective.Sixteen healthy male participants were recruited. After determination of their PTS, five speeds of walking and running were defined. Kinematic data, including center-of-mass (COM) displacement, COM acceleration, and electromyography (EMG) data of rectus femoris (RF), biceps femoris, gastrocnemius (GAS), and tibialis anterior were collected at the five speeds for both walking and running.The vertical COM displacement and acceleration in running were significantly larger than those in walking at all five speeds (p0.05). EMG signals of the two antigravity muscles, RF and GAS, demonstrated a significant higher activation in walking than that in running at the speed beyond PTS (p0.05).The larger energy consumption in walking than that in running beyond the PTS may be attributed to the high activation of lower-extremity muscles. The smaller vertical COM displacements and accelerations exhibited when participants walked beyond the PTS rather than ran did not indicate adverse effects of using walking beyond the PTS as an exercise prescription for boosting energy consumption.