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Introduction: Follicle stimulating hormone (FSH) is identified to play a role in postmenopausal disease and hypothesized to affect abdominal aortic aneurysm (AAA) onset/progression in postmenopausal women. We aimed to detect FSHR gene expression in AAA tissue and cell types involved in AAA formation., Methods: FSH stimulation of human umbilical cord endothelial cells (HUVECs), smooth muscle cells (HUCs) and PMA-differentiated macrophages to assess gene expression of FSHR and various markers. Human macrophages activated with various stimuli were assessed for FSHR gene expression. AAA dataset, AAA tissue samples and AAA-derived smooth muscle cells (SMC) obtained from elderly female donors were assessed for FSHR gene expression. AAA-SMCs were stimulated with FSH to assess its effect on gene expression. Lastly, oxidized low-density-lipoprotein (ox-LDL) uptake and abundance of cell surface protein markers were assessed by flow cytometry after FSH stimulation of human monocytes., Results: FSH stimulation showed similar levels of gene expression in HUVECs and HUCs. Only ACTA2 was downregulated in HUCs. In PMA-differentiated macrophages, gene expression of inflammation markers was unchanged after FSH stimulation. FSHR gene expression was found to be low in the AAA datasets. Female AAA-SMCs show occasional FSHR gene expression at a very low level, yet stimulation with FSH did not affect gene expression of SMC- or inflammation markers. FSH stimulation did not impact ox-LDL uptake or alter cell surface protein expression in monocytes. While FSHR gene expression was detected in human testis tissue, it was below quantification level in all other investigated cell types, even upon activation of macrophages with various stimuli., Conclusion: Despite previous reports, we did not detect FSHR gene expression in various extragonadal cell types, except in occasional female AAA-SMCs. No clear effect on cell activation was observed upon FSH stimulation in any cell type. Our data suggest that a direct effect of FSH in AAA-related extragonadal cells is unlikely to influence AAA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tedjawirja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study investigated how peripheral axonal excitability changes in ischemic stroke patients with hemiparesis or hemiplegia, reflecting the plasticity of motor axons due to corticospinal tract alterations along the poststroke stage., Methods: Each subject received a clinical evaluation, nerve conduction study, and nerve excitability test. Nerve excitability tests were performed on motor median nerves in paretic and non-paretic limbs in the acute stage of stroke. Control nerve excitability test data were obtained from age-matched control subjects. Some patients underwent excitability examinations several times in subacute or chronic stages., Results: A total of thirty patients with acute ischemic stroke were enrolled. Eight patients were excluded due to severe entrapment neuropathy in the median nerve. The threshold current for 50% compound muscle action potential (CMAP) was higher in paretic limbs than in control subjects. Furthermore, in the cohort with severe patients (muscle power ≤ 3/5 in affected hands), increased threshold current for 50% CMAP and reduced subexcitability were noted in affected limbs than in unaffected limbs. In addition, in the subsequent study of those severe patients, threshold electrotonus increased in the hyperpolarization direction: TEh (100-109 ms), and the minimum I/V slope decreased. The above findings suggest the less excitable and less accommodation in lower motor axons in the paretic limb caused by ischemic stroke., Conclusion: Upper motor neuron injury after stroke can alter nerve excitability in lower motor neurons, and the changes are more obvious in severely paretic limbs. The accommodative changes of axons progress from the subacute to the chronic stage after stroke. Further investigation is necessary to explore the downstream effects of an upper motor neuron insult in the peripheral nerve system., Competing Interests: The authors have declared that no competing interests exist.

Objective: Image evaluation strategy for lung cancer patients has difficulty obtaining the appropriate quantity of diffuse lung nodules and bone metastases. The study was to demonstrate whether early variations in the levels of serum 4-tumor markers (4-TMs)(carcinoembryonic antigen [CEA], cancer antigen [CA]125, CA19-9, and CA15-3) after TKI targeted therapy were associated with treatment response in patients with lung adenocarcinoma., Methods: Patients with stage IIIB-IV lung adenocarcinoma taking epidermal growth factor receptor (EGFR) TKIs or anaplastic lymphoma kinase (ALK) inhibitors were enrolled prospectively from June 2012 to February 2015. According to the variations of the percentage of change in 4-TM levels (4-TMpc), we divided patients into ascending (increases in 4-TMpc over the 7th- 14th day) and descending (decreases in 4-TMpc over the 7th- 14th day) groups., Results: 184 patients were enrolled, and 89% had at least one of the pre-treatment evaluable TMs and were further analyzed. An excellent response to the TKI targeted therapy was accurately predicted in the descending group, as determined using receiver operating characteristic curve analysis (an area under the curve, 0.83). Multivariate Cox hazards model analyses demonstrated that the type of 4-TMpc and mutation status were the strongest predictors of progression-free survival (PFS)(descending versus ascending, hazard ratios [HR] 0.30, 95% confidence interval [CI], 0.19-0.47; sensitive mutation versus wide type, HR 0.30, 95% CI, 0.19-0.48)., Conclusions: Type of 4-TMpc 14 days after TKI targeted therapy is associated with an image response and PFS, without regarding mutation status, in patients with advanced lung adenocarcinoma., Competing Interests: The authors have declared that no competing interests exist.

Background: It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 diabetes (T1DM) has rarely been explored., Aim: We investigated whether patients with T1DM are at a relatively high risk of VTE development., Methods: We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM., Results: During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60., Conclusion: T1DM appears to be an independent risk factor for VTE development., Competing Interests: The authors have declared that no competing interests exist.

Background: Few studies have evaluated whether people infected with human immunodeficiency virus (HIV) are at an increased risk of stroke in an Asian population. We investigated the association between HIV infection and the risk of developing stroke by age, calendar year of HIV diagnosis, and follow-up duration in Taiwan., Methods: Using the claims data of a universal health insurance program, we identified 5,961 patients with HIV and 23,844 matched non-HIV subjects without previous stroke from 1998 to 2005 and followed them up until the end of 2011 to measure the incidence of stroke. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with the non-HIV group as reference., Results: During a median follow-up of 8 years, the incidence rates for total, ischemic, and hemorrhagic stroke per 1000 person-years were 2.12, 1.22, and 0.60, respectively, in patients with HIV infection, and 1.98, 1.14, and 0.54, respectively, in the comparison group. HIV infection was associated with an elevated risk of developing total stroke (adjusted HR [95% CI], 1.57 [1.15-2.14]) and ischemic stroke (1.91 [1.25-2.91]) in patients aged less than 45 years, but no association was observed in other age groups (P for interaction with age, p = 0.048 and 0.024, respectively). Patients diagnosed with HIV infection in 1998-1999 had a greater HR for total stroke and ischemic stroke than those diagnosed in 2000-2002 and 2003-2005 (P for interaction, for total stroke p = 0.034, for ischemic stroke p = 0.056). The HRs did not differ by follow-up duration., Conclusions: HIV infection among a young age group is associated with increased risk of developing overall and ischemic stroke. The findings highlight the importance of screening and correcting risk factors for young stroke prevention immediately and aggressively., Competing Interests: The authors have declared that no competing interests exist.

Background: Dystonia is a neurological syndrome typically resulting in abnormal postures., Objectives: We tested the role of physical injury as potential risk factor for development of dystonia using The National Health Insurance Research Database of Taiwan., Methods: We identified 65704 people who were coded in the database as having had peripheral traumatic injuries (ICD-9-CM 807-848 and 860-959) in the year 2000. Patients with traumatic brain or spine injuries were excluded from analysis. We matched them using purposive sampling with 65704 people in the database who had not suffered peripheral trauma. We looked then at the incidence of dystonia occurring at least 1 year from the date of the peripheral trauma until 2011. Psychiatric symptoms (depression and anxiety) and sleeps difficulties have been investigated as potential covariates., Results: We found 189 patients with dystonia (0.28%) in the trauma group, and 52 patients with dystonia (0.08%) in the non-trauma group. Trauma was independently associated with dystonia (adjusted HR = 3.12, 95% CI = 2.30-4.24). The incidence density of dystonia in the trauma group was 2.27 per 10000 person-years, while it was 0.71 per 10000 person-years in the non-trauma group Beyond the peripheral trauma, other variables associated to the incidence of dystonia included female sex, aged 40 years and above, depression and sleep disorders., Conclusion: These data from a large population dataset support traumatic injury as a risk factor for the development of dystonia., Competing Interests: The authors have declared that no competing interests exist.

Opioid addiction is a major public health issue worldwide. Methadone maintenance treatment (MMT) is used to detoxify users of illicit opiates, but drug relapse is common and associated with poor quality of life (QoL). This study investigated the associations between the GRIN3A, GRM6, and TPH2 genetic variants and QoL in the MMT population. A total of 319 participants were included in the study, and genotyping of GRIN3A, GRM6, and TPH2 genes was performed using the Sequenom iPLEX. Associations between genotypes and the domains of QoL were examined through posthoc analysis with LSMEANS syntax using SAS 9.1.3. The single nucleotide polymorphisms rs9325202 and rs1487275 in the TPH2 gene were significantly associated with the QoL domain of physical functioning. The least absolute shrinkage and selection operator regression model revealed that the risk allele rs1487275-G was significantly correlated with the domain of physical functioning when clinical characteristics were considered as covariates. The results of the present study illuminate the importance of the genetic basis of QoL in the MMT population, and suggest that genotypes should be considered as a potential QoL indicator., Competing Interests: The authors have declared that no competing interests exist.

Objective: This population-based cohort study investigated the risk of developing peripheral arterial occlusive disease (PAOD) in patients with Bell's palsy., Methods: We used longitudinal claims data of health insurance of Taiwan to identify 5,152 patients with Bell's palsy newly diagnosed in 2000-2010 and a control cohort of 20,608 patients without Bell's palsy matched by propensity score. Incidence and hazard ratio (HR) of PAOD were assessed by the end of 2013., Results: The incidence of PAOD was approximately 1.5 times greater in the Bell's palsy group than in the non-Bell's palsy controls (7.75 vs. 4.99 per 1000 person-years). The Cox proportional hazards regression analysis measured adjusted HR was 1.54 (95% confidence interval (CI) = 1.35-1.76) for the Bell's palsy group compared to the non-Bell's palsy group, after adjusting for sex, age, occupation, income and comorbidities. Men were at higher risk of PAOD than women in the Bell's palsy group, but not in the controls. The incidence of PAOD increased with age in both groups, but the Bell's palsy group to control group HR of PAOD decreased as age increased. The systemic steroid treatment reduced 13% of PAOD hazard for Bell's palsy patients, compared to those without the treatment, but not significant., Conclusions: Bell's palsy appears to be associated with an increased risk of developing PAOD. Further pathophysiologic, histopathology and immunologic research is required to explore the underlying biologic mechanism.

Environmental impacts can alter relationships between a coral and its symbiotic microbial community. Furthermore, changes in the microbial community associated with increased seawater temperatures can cause opportunistic infections, coral disease and death. Interactions between soft corals and their associated microbes are not well understood. The species Scleronephthya gracillimum is distributed in tropical to temperate zones in coral assemblages along the Kuroshio Current region. In this study we collected S. gracillimum from various sites at different latitudes, and compared composition of their bacterial communities using Next Generation Sequencing. Coral samples from six geographically distinct areas (two sites each in Taiwan, Japan, and Korea) had considerable variation in their associated bacterial communities and diversity. Endozoicimonaceae was the dominant group in corals from Korea and Japan, whereas Mycoplasma was dominant in corals from Taiwan corals. Interestingly, the latter corals had lower relative abundance of Endozoicimonaceae, but greater diversity. These biogeographic differences in bacterial composition may have been due to varying environmental conditions among study locations, or because of host responses to prevailing environmental conditions. This study provided a baseline for future studies of soft coral microbiomes, and assessment of functions of host metabolites and soft coral holobionts.

To characterize and interpret arterial spin labeling (ASL) reactive hyperemia of calf muscles for a better understanding of the microcirculation in peripheral arterial disease (PAD), we present a physiological model incorporating oxygen transport, tissue metabolism, and vascular regulation mechanisms. The model demonstrated distinct effects between arterial stenoses and microvascular dysfunction on reactive hyperemia, and indicated a higher sensitivity of 2-minute thigh cuffing to microvascular dysfunction than 5-minute cuffing. The recorded perfusion responses in PAD patients (n = 9) were better differentiated from the normal subjects (n = 7) using the model-based analysis rather than characterization using the apparent peak and time-to-peak of the responses. The analysis results suggested different amounts of microvascular disease within the patient group. Overall, this work demonstrates a novel analysis method and facilitates understanding of the physiology involved in ASL reactive hyperemia. ASL reactive hyperemia with model-based analysis may be used as a noninvasive microvascular assessment in the presence of arterial stenoses, allowing us to look beyond the macrovascular disease in PAD. A subgroup who will have a poor prognosis after revascularization in the patients with critical limb ischemia may be associated with more severe microvascular diseases, which may potentially be identified using ASL reactive hyperemia.

Objectives: The risk of herpes zoster (HZ) between patients with psoriasis receiving and not receiving systemic therapy has received increasing attention. This study investigated the association of psoriasis with the risk of HZ., Methods: We conducted a population-based retrospective cohort study by using the Taiwan National Health Insurance Research Database. The psoriasis cohort consisted of 4077 patients with newly diagnosed psoriasis between 2000 and 2006. Each patient with psoriasis was frequency-matched with four people without psoriasis, by sex, age and index year. (nonpsoriasis cohort; 16308 subjects). Patients who received systemic therapy were classified as having severe psoriasis, whereas those who did not receive systemic therapy were classified as having mild psoriasis. The Cox proportional hazards regression analysis was conducted to estimate the association between psoriasis and HZ risk., Results: The overall incidence density rate of HZ in the psoriasis cohort than in the nonpsoriasis cohort (4.50 vs. 3.44 per 1,000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.29 [95% confidence interval (CI) = 1.07-1.56]. In additional, compared with the nonpsoriasis cohort, the risk of HZ was higher in the severe psoriasis cohort than in the nonpsoriasis cohort (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.15-2.27). The comparison between psoriasis and nonpsoriasis cohorts revealed a greatest magnitude risk of HZ in women (adjusted HR, 1.36; 95% CI, 1.04-1.79), study participants in the age group of 20-39 years (adjusted HR, 1.77; 95% CI, 1.17-2.66), and study participants without any comorbidities (adjusted HR, 1.37; 95% CI, 1.02-1.84)., Conclusions: Our results suggest that psoriasis is associated with an increased risk of HZ, which involves differences in sex and age. Although systemic therapy may have a major role in the risk of HZ, the intrinsic factors of psoriasis cannot be excluded.

Purpose: To examine the long-term risk of essential tremor (ET) in migraine., Methods: Using population-based administrative data from a subset of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22,696 newly diagnosed migraineurs (mean age 44.5 years) and a matched migraine-free cohort of 90,784 individuals in the period 2000-2008. Multivariable Cox proportional hazards regression analysis was conducted for assessing the ET risk for the migraine cohort compared to the migraine-free cohort., Results: After adjusting for covariates, the migraine cohort had a 1.83-fold increased risk (95% CI 1.50-2.23) of subsequent ET in comparison to the migraine-free cohort (8.97 vs. 4.81 per 10,000 person-years). In the subgroup analysis, patients with migraine were associated with higher risks of ET, regardless of gender, age or the existence of comorbidities., Conclusion: Our findings demonstrated an association between migraine and ET, suggesting a possible shared pathophysiology underpinning both disorders.

The study aimed to illustrate the constructs and test the psychometric properties of an instrument of health literacy competencies (IOHLC) for health professionals. A multi-phase questionnaire development method was used to develop the scale. The categorization of the knowledge and practice domains achieved consensus through a modified Delphi process. To reduce the number of items, the 92-item IOHLC was psychometrically evaluated through internal consistency, Rasch modeling, and two-stage factor analysis. In total, 736 practitioners, including nurses, nurse practitioners, health educators, case managers, and dieticians completed the 92-item IOHLC online from May 2012 to January 2013. The final version of the IOHLC covered 9 knowledge items and 40 skill items containing 9 dimensions, with good model fit, and explaining 72% of total variance. All domains had acceptable internal consistency and discriminant validity. The tool in this study is the first to verify health literacy competencies rigorously. Moreover, through psychometric testing, the 49-item IOHLC demonstrates adequate reliability and validity. The IOHLC may serve as a reference for the theoretical and in-service training of Chinese-speaking individuals' health literacy competencies.

Background: Many people are concerned about that the quality of preventive care for patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is suboptimal. Taiwan, a hyperendemic area of chronic HBV and HCV infection, implemented a nationwide pay-for-performance (P4P) program in 2010, which aimed to improve the preventive care provided to HBV and HCV patients by increasing physicians' adherence to guidelines through financial incentives. The objective of this study was to evaluate the early effects of the P4P program on utilization of preventive services by HBV and HCV patients., Methods: Using a quasi-experimental design with propensity score matching method, we matched the HBV and HCV patients enrolled in the P4P program with non-enrollees in 2010, resulting in 21,643 patients in each group. Generalized estimating equations was applied to examine the difference-in-difference effects of P4P program enrollment on the utilization of three guideline-recommended preventive services (regular outpatient follow-up visits, abdominal ultrasonography (US) examinations, and aspartate aminotransferase and alanine aminotransferase (AST/ALT) tests by HBV and HCV patients., Results: The P4P program enrollees were significantly more likely to attend twice-annual follow-up visits, to receive recommended US examinations and AST/ALT tests, than non-enrollees., Conclusions: The results of our preliminary assessment indicate that financial incentives offered by the P4P program was associated with a modest improvement in adherence to guidelines for better chronic HBV and HBC management.

Adolescent obesity has increased to alarming proportions globally. However, few studies have investigated the optimal waist circumference (WC) of Asian adolescents. This study sought to establish the optimal WC cutoff points that identify a cluster of cardiovascular risk factors (CVRFs) among 15-year-old ethnically Chinese adolescents. This study was a regional population-based study on the CVRFs among adolescents who enrolled in all the senior high schools in Taipei City, Taiwan, between 2011 and 2014. Four cross-sectional health examinations of first-year senior high school (grade 10) students were conducted from September to December of each year. A total of 124,643 adolescents aged 15 (boys: 63,654; girls: 60,989) were recruited. Participants who had at least three of five CVRFs were classified as the high-risk group. We used receiver-operating characteristic curves and the area under the curve (AUC) to determine the optimal WC cutoff points and the accuracy of WC in predicting high cardiovascular risk. WC was a good predictor for high cardiovascular risk for both boys (AUC: 0.845, 95% confidence interval [CI]: 0.833-0.857) and girls (AUC: 0.763, 95% CI: 0.731-0.795). The optimal WC cutoff points were ≥78.9 cm for boys (77th percentile) and ≥70.7 cm for girls (77th percentile). Adolescents with normal weight and an abnormal WC were more likely to be in the high cardiovascular risk group (odds ratio: 3.70, 95% CI: 2.65-5.17) compared to their peers with normal weight and normal WC. The optimal WC cutoff point of 15-year-old Taiwanese adolescents for identifying CVRFs should be the 77th percentile; the 90th percentile of the WC might be inadequate. The high WC criteria can help health professionals identify higher proportion of the adolescents with cardiovascular risks and refer them for further evaluations and interventions. Adolescents' height, weight and WC should be measured as a standard practice in routine health checkups.

Purpose: The changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant., Methods: We used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity., Results: The mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46-0.94)., Conclusion: Parathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism.

Purpose: The association between primary headaches, including tension-type headache (TTH) as one of the most common primary headache disorders, and dementia remains controversial. In this nationwide, population-based, retrospective, cohort study, we explored the potential association between TTH and dementia and examined sex, age, and comorbidities as risk factors for dementia., Methods: Using the Taiwan National Health Insurance Research Database (NHIRD) claims data, the sample included 13908 subjects aged ≥20 years with newly-diagnosed TTH in 2000-2006. The non-TTH group included 55632 randomly selected sex- and age-matched TTH-free individuals. All subjects were followed until dementia diagnosis, death, or the end of 2011. Patients with dementia, including vascular and non-vascular (including Alzheimer's) subtypes, were identified using International Classification of Diseases Ninth Revision, Clinical Modification codes. Multivariate Cox proportional hazards regression models were used to assess the risk of dementia and dementia-associated risk factors, such as migraine and other medical comorbidities., Results: During the average follow-up of 8.14 years, the incidence density rates of dementia were 5.30 and 3.68/1,000 person-years in the TTH and non-TTH groups, respectively. Compared with the non-TTH group, the risks of dementia were 1.25 (95% confidence interval [CI], 1.11-1.42) and 1.13 (95% CI, 1.01-1.27) times higher in the women and >65-year-old TTH group, respectively. TTH patients with comorbidities had a higher risk of dementia. TTH patients had a greater risk of non-vascular dementia (hazard ratio, 1.21; 95% CI, 1.09-1.34) than the non-TTH group., Conclusion: TTH patients have a future risk of dementia, indicating a potentially linked disease pathophysiology that warrants further study. The association between TTH and dementia is greater in women, older adults, and with comorbidities. Clinicians should be aware of potential dementia comorbidity in TTH patients.

Pigment epithelium-derived factor (PEDF) is a multifunctional protein that exhibits anti-angiogenic, antitumor, anti-inflammatory, antioxidative, anti-atherogenic, and cardioprotective properties. While it was recently shown that PEDF expression is inhibited under low oxygen conditions, the functional role of PEDF in response to hypoxia/reoxygenation (H/R) remains unclear. The goal of this study was to therefore investigate the influence of PEDF on myocardial H/R injury. For these analyses, PEDF-specific small interfering RNA-expressing and PEDF-expressing lentivirus (PEDF-LV) vectors were utilized to knockdown or stably overexpress PEDF, respectively, within human cardiomyocytes (HCM) in vitro. We noted that reactive oxygen species (ROS) play important roles in the induction of cell death pathways, including apoptosis and autophagy in ischemic hearts. Our findings demonstrate that overexpression of PEDF resulted in a significant reduction in ROS production and attenuation of mitochondrial membrane potential depletion under H/R conditions. Furthermore, PEDF inhibited the activation of a two-step apoptotic pathway in which caspase-dependent (caspase-9 and caspase-3) and caspase-independent (apoptosis inducing factor and endonuclease G), which in turn cleaves several crucial substrates including the DNA repair enzyme poly (ADP-ribose) polymerase. Meanwhile, overexpression of PEDF also promoted autophagy, a process that is typically activated in response to H/R. Therefore, these findings suggest that PEDF plays a critical role in preventing H/R injury by modulating anti-oxidant and anti-apoptotic factors and promoting autophagy.

Objective: The purpose of our study was to determine the association of type 1 diabetes mellitus (T1DM) and the risk of herpes zoster (HZ)., Methods: In this cohort study, we selected 4736 patients with T1DM registered in the Catastrophic Illness Patient Database who received insulin therapy before 2003 and 18944 participants without DM who were selected by frequency matched based on sex and age. Cox proportional hazard regression analysis was used to measure the hazard ratios (HRs) of HZ in the T1DM group compared with that in the non-T1DM group., Results: Cox proportional hazard regression analysis showed that the adjusted HR of HZ was 2.38 times higher for patients in the T1DM group (95% CI = 1.77-3.19) than for those in the non-T1DM group. According to diabetes severity, mild and serious T1DM patients were associated with a higher risk of HZ (adjusted HR = 2.26, 95% CI = 1.67-3.05; and adjusted HR = 5.08, 95% CI = 2.66-9.71, respectively) than subjects without T1DM., Conclusion: Patients with T1DM are at a higher risk of HZ than those without T1DM.

Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.

We analyzed the occurrence and mechanisms of fusidic acid resistance present in staphylococci isolated from 59 healthy volunteers. The fingers of the volunteers were screened for the presence of staphylococci, and the collected isolates were tested for resistance to fusidic acid. A total of 34 fusidic acid resistant staphylococcal strains (all were coagulase-negative) were isolated from 22 individuals (22/59, 37.3%). Examination of the resistance genes revealed that acquired fusB or fusC was present in Staphylococcus epidermidis, Staphylococcus capitis subsp. urealyticus, Staphylococcus hominis subsp. hominis, Staphylococcus warneri and Staphylococcus haemolyticus. Resistance islands (RIs) carrying fusB were found in S. epidermidis and S. capitis subsp. urealyticus, while staphylococcal chromosome cassette (SCC)-related structures harboring fusC were found in S. hominis subsp. hominis. Genotypic analysis of S. epidermidis and S. hominis subsp. hominis indicated that the fus elements were disseminated in diverse genetic strain backgrounds. The fusC elements in S. hominis subsp. hominis strains were highly homologous to SCCfusC in the epidemic sequence type (ST) 239/SCCmecIII methicillin-resistant S. aureus (MRSA) or the pseudo SCCmec in ST779 MRSA. The presence of acquired fusidic acid resistance genes and their genetic environment in commensal staphylococci suggested that the skin commensal staphylococci may act as reservoir for fusidic acid resistance genes.

Background: Preterm newborns that receive oxygen therapy often develop bronchopulmonary dysplasia (BPD), which is abnormal lung development characterized by impaired alveologenesis. Oxygen-mediated injury is thought to disrupt normal lung growth and development. However, the mechanism of hyperoxia-induced BPD has not been extensively investigated. We established a neonatal mouse model to investigate the effects of normobaric hyperoxia on retinoid metabolism and retinoid receptor expression., Methods: Newborn mice were exposed to hyperoxic or normoxic conditions for 15 days. The concentration of retinol and retinyl palmitate in the lung was measured by HPLC to gauge retinoid metabolism. Retinoid receptor mRNA levels were assessed by real-time PCR. Proliferation and retinoid receptor expression in A549 cells were assessed in the presence and absence of exogenous vitamin A., Results: Hyperoxia significantly reduced the body and lung weight of neonatal mice. Hyperoxia also downregulated expression of RARα, RARγ, and RXRγ in the lungs of neonatal mice. In vitro, hyperoxia inhibited proliferation and expression of retinoid receptors in A549 cells., Conclusion: Hyperoxia disrupted retinoid receptor expression in neonatal mice.

Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA) is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR) injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877), 1.71% (15/877), and 2.62% (23/877) of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB) (Alb, Fga, and Trf), suppressed excitotoxicity (Grm5, Gnai, and Gdi), and enhanced energy metabolism (Bdh), thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3) and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

Background: The aim of this study was to determine the annual trends of traditional Chinese medicine (TCM) use for prevalent and incident asthmatic adults in Taiwan from 2000 to 2011. The annual prevalence and incidence of asthma in adults among subgroups of sociodemographic factors were also investigated., Methods: A population-based study was conducted using a random sample with one million beneficiaries of all residents aged ≥18 years enrolled in the National Health Insurance program. Adults diagnosed with asthma were identified from the National Health Insurance Research Database. The annual prevalence and incidence of asthma in the adult population were estimated by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes to identify relevant cases from 2000 to 2011., Results: The number of annual prevalent cases of diagnosed asthma increased from 56,885 in 2000 to 101,535 in 2011. The prevalence increased significantly on annual basis, whereas the incidence rate fluctuated over time. The prevalence of TCM use by adults with asthma decreased significantly (p<0.05), from 38.58% in 2000 to 29.26% in 2011. The number of annual incident cases of diagnosed asthma decreased from 3,896 in 2000 to 2,684 in 2011. TCM use rates in asthma incident adults decreased significantly (p<0.05), from 54.24% in 2000 to 38.19% in 2011., Conclusion: The prevalence of TCM utilization is high among adults with asthma in Taiwan. However, our study demonstrated a substantial decrease in the annual prevalence of TCM use by prevalent and incident asthmatic adults in Taiwan from 2000 to 2011. In addition, the prevalence of TCM use was higher among incident cases, compared with those with prevalent cases.

Objective: Combinations of Chinese herbal products (CHPs) are widely used for ischemic heart disease (IHD) in Taiwan. We analyzed the usage and frequency of CHPs prescribed for patients with IHD., Methods: A nationwide population-based cross-sectional study was conducted, 53531 patients from a random sample of one million in the National Health Insurance Research Database (NHIRD) from 2000 to 2010 were enrolled. Descriptive statistics, the multiple logistic regression method and Poisson regression analysis were employed to estimate the adjusted odds ratios (aORs) and adjusted risk ratios (aRRs) for utilization of CHPs., Results: The mean age of traditional Chinese medicine (TCM) nonusers was significantly higher than that of TCM users. Zhi-Gan-Cao-Tang (24.85%) was the most commonly prescribed formula CHPs, followed by Xue-Fu-Zhu-Yu-Tang (16.53%) and Sheng-Mai-San (16.00%). The most commonly prescribed single CHPs were Dan Shen (29.30%), Yu Jin (7.44%), and Ge Gen (6.03%). After multivariate adjustment, patients with IHD younger than 29 years had 2.62 times higher odds to use TCM than those 60 years or older. Residents living in Central Taiwan, having hyperlipidemia or cardiac dysrhythmias also have higher odds to use TCM. On the contrary, those who were males, who had diabetes mellitus (DM), hypertension, stroke, myocardial infarction (MI) were less likely to use TCM., Conclusions: Zhi-Gan-Cao-Tang and Dan Shen are the most commonly prescribed CHPs for IHD in Taiwan. Our results should be taken into account by physicians when devising individualized therapy for IHD. Further large-scale, randomized clinical trials are warranted in order to determine the effectiveness and safety of these herbal medicines.

Plant growth and development is often regulated by the interaction of environmental factors such as light and various phytohormones. Arabidopsis FAR-RED INSENSITIVE 219 (FIN219)/JASMONATE RESISTANT 1 (JAR1) participates in phytochrome A-mediated far-red (FR) light signaling and interacts with different light signaling regulators. FIN219/JAR1 is a jasmonic acid (JA)-conjugating enzyme responsible for the formation of JA-isoleucine. However, how FIN219/JAR1 integrates FR light and JA signaling remains largely unknown. We used a microarray approach to dissect the effect of fin219 mutation on the interaction of FR light and JA signaling. The fin219-2 mutant was less sensitive than the wild type to various concentrations of methyl jasmonate (MeJA) under low and high FR light. High FR light reduced the sensitivity of Arabidopsis seedlings to MeJA likely through FIN219. Intriguingly, in response to MeJA, FIN219 levels showed a negative feedback regulation. Further microarray assay revealed that FR light could regulate gene expression by FIN219-dependent or -independent pathways. The expression profiles affected in fin219-2 indicated that FIN219/JAR1 plays a critical role in the integration of multiple hormone-related signaling. In particular, FIN219 regulates a number of transcription factors (TFs), including 94 basic helix-loop-helix (bHLH) TFs, in response to FR light and MeJA. Loss-of-function mutants of some bHLH TFs affected by FIN219 showed altered responses to MeJA in the regulation of hypocotyl and root elongation. Thus, FIN219/JAR1 is tightly regulated in response to exogenous MeJA. It also interacts with multiple plant hormones to modulate hypocotyl and root elongation of Arabidopsis seedlings likely by regulating a group of TFs.

Background: An association between lichen simplex chronicus (LSC) and sexual dysfunction was explored. However, no data are available from investigations into the relationship between erectile dysfunction (ED) and LSC., Objectives: This retrospective population-based cohort study aimed to clarify the risk of ED associated with LSC., Methods: By using the Taiwan National Health Insurance Research dataset, we identified 5611 male patients who had been newly diagnosed with LSC from 2000 to 2004. The date of diagnosis was identified as the index date. LSC patients with incomplete demographic information or with a history of ED before the index date were excluded. In total, 22444 age-matched patients without LSC were randomly selected as the non-LSC group based on a 1:4 ratio. Subsequence occurrence of ED was measured until 2011. The association between LSC and the risk of developing ED was estimated using Cox proportional hazard regression model., Results: After adjusting for age and comorbidities, patients with LSC had a 1.74-fold greater risk of developing ED compared with those without LSC (95% confidence interval=1.44-2.10). LSC patients with comorbidities including diabetes, hyperlipidemia, hypertension, cardiovascular disease, peripheral arterial disease, chronic obstructive pulmonary disease, chronic kidney disease, depression, and anxiety were at a higher risk of ED compared with the non-LSC patients without comorbidities., Conclusions: LSC confers a greater risk in the development of ED. Physicians should be aware of the potential of ED occurrence in LSC patients.

Lung epithelial and endothelial cell death accompanied by inflammation contributes to hyperoxia-induced acute lung injury (ALI). Impaired resolution of ALI can promote and/or perpetuate lung pathogenesis, including fibrosis. Previously, we have shown that the transcription factor Nrf2 induces cytoprotective gene expression and confers protection against hyperoxic lung injury, and that Nrf2-mediated signaling is also crucial for the restoration of lung homeostasis post-injury. Although we have reported that PI3K/AKT signaling is required for Nrf2 activation in lung epithelial cells, significance of the PI3K/AKT-Nrf2 crosstalk during hyperoxic lung injury and repair remains unclear. Thus, we evaluated this aspect using Nrf2 knockout (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mouse models. Here, we show that pharmacologic inhibition of PI3K/AKT signaling increased lung inflammation and alveolar permeability in Nrf2(+/+) mice, accompanied by decreased expression of Nrf2-target genes such as Nqo1 and Hmox1. PI3K/AKT inhibition dampened hyperoxia-stimulated Nqo1 and Hmox1 expression in lung epithelial cells and alveolar macrophages. Contrasting with its protective effects, PI3K/AKT inhibition suppressed lung inflammation in Nrf2(+/+) mice during post-injury. In Nrf2(-/-) mice exposed to room-air, PI3K/AKT inhibition caused lung injury and inflammation, but it did not exaggerate hyperoxia-induced ALI. During post-injury, PI3K/AKT inhibition did not augment, but rather attenuated, lung inflammation in Nrf2(-/-) mice. These results suggest that PI3K/AKT-Nrf2 signaling is required to dampen hyperoxia-induced lung injury and inflammation. Paradoxically, the PI3K/AKT pathway promotes lung inflammation, independent of Nrf2, during post-injury.

Motor impairment after stroke is related to the integrity of the corticospinal tract (CST). However, considerable variability in motor impairment remains unexplained. To increase the accuracy in evaluating long-term motor function after ischemic stroke, we tested the hypothesis that combining diffusion tensor imaging (DTI) and gray matter (GM) volumetry can better characterize long-term motor deficit than either method alone in patients with chronic stroke. We recruited 31 patients whose Medical Research Council strength grade was ≤ 3/5 in the extensor muscles of the affected upper extremity in the acute phase. We used the Upper Extremity Fugl-Meyer (UE-FM) assessment to evaluate motor impairment, and as the primary outcome variable. We computed the fractional anisotropy ratio of the entire CST (CSTratio) and the volume of interest ratio (VOIratio), between ipsilesional and contralesional hemispheres, to explain long-term motor impairment. The results showed that CSTratio, VOIratio of motor-related brain regions, and VOIratio in the temporal lobe were correlated with UE-FM. A multiple regression model including CSTratio and VOIratio of the caudate nucleus explained 40.7% of the variability in UE-FM. The adjusted R2 of the regression model with CSTratio as an independent variable was 29.4%, and that of using VOIratio of the caudate nucleus as an independent variable was 23.1%. These results suggest that combining DTI and GM volumetry may achieve better explanation of long-term motor deficit in stroke patients, than using either measure individually. This finding may provide guidance in determining optimal neurorehabilitative interventions.

Background: It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations., Methods: This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2)., Results: From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age., Conclusion: This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.

Objectives: Few studies have evaluated the association between Sjogren's syndrome (SS) and respiratory failure (RF). Thus, we conducted a retrospective national cohort study to investigate whether Sjogren's syndrome (SS) increases the risk of respiratory failure (RF)., Methods: The cohort consisted of 4954 newly diagnosed patients with SS but without a previous diagnosis of RF, and 19816 patients as the comparison cohort from the catastrophic illnesses registry, obtained from the 2000-2005 period. All of the study participants were followed from the index date to December 31, 2011. We analyzed the association between the risk of RF and SS by using a Cox proportional hazards regression model, controlling for sex, age, and comorbidities., Results: The overall incidence rate of RF showed a 3.21-fold increase in the SS cohort compared with the comparison cohort. The adjusted HR of RF was 3.04 for the SS cohort compared with the comparison cohort, after we adjusted for sex, age, and comorbidities. The HRs of RF for patients with primary SS and secondary SS compared with the comparison cohort were 2.99 and 3.93, respectively (P for trend <.001). The HRs of RF increased as the severity of SS increased, from 2.34 for those with no inpatient care experience to 5.15 for those with inpatient care experience (P for trend <.001)., Conclusion: This study indicates that clinical physicians should not only consider secondary SS but also primary SS as a critical factor that increases the risk of RF.

Background: Previous studies have suggested that chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. There are some evidence that people with diabetes are at a risk of developing many forms of cancer, but inconclusive with regard to lung cancer. The aim of this study was to evaluate whether COPD with or without type 2 diabetes mellitus (T2DM) influences the risk of developing lung cancer., Methods: This is a retrospective cohort study consisting of 20,730 subjects newly diagnosed with COPD ("cases"). Their data was collected from the National Health Insurance system of Taiwan from 1998 to 2010. Among these patients, 5,820 patients had T2DM and 14,910 patients did not have T2DM. The retrospective matched control group consisted of 20,729 subjects without either COPD or T2DM. The control group was matched with the cases for sex, age, and index year (the year that the patient was diagnosed with COPD). The subjects were followed until the end of 2011., Results: The findings of our study showed that the risk of lung cancer was higher in the COPD group than in the non-COPD group, with adjusted hazard ratio (HR) of 5.02 [95% confidence interval (CI) = 4.23-5.94] among total case group, adjusted HR was 5.38 (95% CI = 4.52-6.40) in the cohort without T2DM and adjusted HR was 4.05 (95% CI = 3.26-5.03) in the cohort with T2DM. We observed a significantly protective effect from lung cancer (adjusted HR = 0.75, 95% CI = 0.63-0.90) of diabetic cohort than non-diabetic cohort among patients with COPD., Conclusion: Patients with COPD had a significantly higher risk of developing lung cancer than healthy people. However, there was a protective effect of T2DM for lung cancer among patients with COPD. Further investigation may be needed to corroborate the mechanism or bring up reliable reasons.

TDP-43 is found in cytoplasmic inclusions in 95% of amyotrophic lateral sclerosis (ALS) and 60% of frontotemporal lobar degeneration (FTLD). Approximately 4% of familial ALS is caused by mutations in TDP-43. The majority of these mutations are found in the glycine-rich domain, including the variant M337V, which is one of the most common mutations in TDP-43. In order to investigate the use of allele-specific RNA interference (RNAi) as a potential therapeutic tool, we designed and screened a set of siRNAs that specifically target TDP-43(M337V) mutation. Two siRNA specifically silenced the M337V mutation in HEK293T cells transfected with GFP-TDP-43(wt) or GFP-TDP-43(M337V) or TDP-43 C-terminal fragments counterparts. C-terminal TDP-43 transfected cells show an increase of cytosolic inclusions, which are decreased after allele-specific siRNA in M337V cells. We then investigated the effects of one of these allele-specific siRNAs in induced pluripotent stem cells (iPSCs) derived from an ALS patient carrying the M337V mutation. These lines showed a two-fold increase in cytosolic TDP-43 compared to the control. Following transfection with the allele-specific siRNA, cytosolic TDP-43 was reduced by 30% compared to cells transfected with a scrambled siRNA. We conclude that RNA interference can be used to selectively target the TDP-43(M337V) allele in mammalian and patient cells, thus demonstrating the potential for using RNA interference as a therapeutic tool for ALS.

Background: Attention deficit is an early and key characteristic of minimal hepatic encephalopathy (MHE) and has been used as indicator for MHE detection. The aim of this study is to classify the cirrhotic patients with or without MHE (NMHE) and healthy controls (HC) using the resting-state attention-related brain network analysis., Methods and Findings: Resting-state fMRI was administrated to 20 MHE patients, 21 NMHE patients, and 17 HCs. Three attention-related networks, including dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN), were obtained by independent component analysis. One-way analysis of covariance was performed to determine the regions of interest (ROIs) showing significant functional connectivity (FC) change. With FC strength of ROIs as indicators, Linear Discriminant Analysis (LDA) was conducted to differentiate MHE from HC or NMHE. Across three groups, significant FC differences were found within DAN (left superior/inferior parietal lobule and right inferior parietal lobule), VAN (right superior parietal lobule), and DMN (bilateral posterior cingulate gyrus and precuneus, and left inferior parietal lobule). With FC strength of ROIs from three networks as indicators, LDA yielded 94.6% classification accuracy between MHE and HC (100% sensitivity and 88.2% specificity) and 85.4% classification accuracy between MHE and NMHE (90.0% sensitivity and 81.0% specificity)., Conclusions: Our results suggest that the resting-state attention-related brain network analysis can be useful in classification of subjects with MHE, NMHE, and HC and may provide a new insight into MHE detection.

Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.

Background: Few studies have examined parent-child resemblance in body weight status using nationally representative data for the US., Design: We analyzed Body Mass Index (BMI), weight status, and related correlates for 4,846 boys, 4,725 girls, and their parents based on US nationally representative data from the 2006 and 2007 Medical Expenditure Panel Survey (MEPS). Pearson partial correlation coefficients, percent agreement, weighted kappa coefficients, and binary and multinomial logistic regression were used to examine parent-child resemblance, adjusted for complex sampling design., Results: Pearson partial correlation coefficients between parent and child's BMI measures were 0.15 for father-son pairs, 0.17 for father-daughter pairs, 0.20 for mother-son pairs, and 0.23 for mother-daughter pairs. The weighted kappa coefficients between BMI quintiles of parent and child ranged from -0.02 to 0.25. Odds ratio analyses found children were 2.1 (95% confidence interval (CI): 1.6, 2.8) times more likely to be obese if only their father was obese, 1.9 (95% CI: 1.5, 2.4) times more likely if only their mother was obese, and 3.2 (95% CI: 2.5, 4.2) times more likely if both parents were obese., Conclusions: Parent-child resemblance in BMI appears weak and may vary across parent-child dyad types in the US population. However, parental obesity status is associated with children's obesity status. Use of different measures of parent-child resemblance in body weight status can lead to different conclusions.

Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time.