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Vaccination helps reduce the risk of coronavirus disease 2019 (COVID-19) infection in elderly individuals with major neurocognitive disorders (MNDs). However, some caregivers are hesitant to have their elderly family members with MNDs vaccinated against COVID-19. This study explored the factors influencing caregivers’ intentions to vaccinate elderly family members with MNDs against COVID-19. A total of 232 caregivers of elderly family members with MNDs participated in this study. In this survey, data regarding COVID-19 vaccination acceptance, fear, side effects, family members’ attitudes toward vaccination, mental health status, neuropsychiatric symptoms, and cognitive impairments were collected from the elderly participants with MNDs. The associations between these variables and the caregivers’ intention to vaccinate their elderly family members with MNDs against COVID-19 were examined using a multivariable linear regression analysis model. The results revealed that caregivers’ perceived familial support for vaccination, the perceived value of vaccination, and autonomy to vaccinate elder family members were positively correlated with caregivers’ intention to vaccinate elderly family members with MNDs, whereas elderly family members’ age was negatively correlated with caregiver intentions. This study demonstrated that caregiver factors (perceived familial support, value of vaccination, and autonomy) and elderly family members’ age were correlated with caregiver intention. These factors should be considered in developing interventions to enhance caregivers’ intentions to vaccinate their elderly family members with MNDs against COVID-19.

Over several years, this study examines how biotic interactions and warming affect the entire marine prokaryotic community at a location off the coast of Southern California. Analyses show that free-living and particle-associated prokaryotes were strongly predicted by phytoplankton and viral communities, and El Niño warming shifted cyanobacteria from cold-water ecotypes to warm-water ecotypes.

Background: Neuropsychiatric symptoms (NPS) could increase mortality risk in people with dementia due to Alzheimer's disease (AD). However, whether NPS affects mortality risk in people with mild cognitive impairment (MCI) and whether any specific syndrome of NPS influences this risk are still unclear. Methods: In total, 984 participants with dementia due to AD, 338 with MCI, and 365 controls were enrolled. Over a mean of 5-year follow-up, cause of death data were obtained from the Ministry of Health and Welfare in Taiwan. NPS were assessed using Neuropsychiatric Inventory Questionnaire (NPI-Q), and psychosis, mood, and frontal domain scores were determined. Survival analyses were conducted to determine the hazard ratio (HR) of death. Results: In controlled analyses, HR of death for AD was 2.19 (95% confidence interval [CI] = 1.29–3.71) compared with the control group, whereas no statistical significance was noted for the MCI group. A high NPI-Q score (above the median score) increased mortality risk for both the MCI and AD groups, with HRs of 2.32 (95% CI = 1.07–5.03) and 2.60 (95% CI = 1.51–4.47), respectively. Among NPI-Q domain scores, only high mood domain, but not psychosis or frontal domain, scores increased death risk for both the MCI (HR = 2.89, 95% CI = 1.00–8.51) and AD (HR = 2.59, 95% CI = 1.47–4.55) groups. Conclusion: Mortality risk is high for patients with AD. Not only for AD, patients with MCI presenting with NPS, particularly mood symptoms, have high death risk.

Background: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients’ clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. Methods: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image’s region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier’s effectiveness, the ROC curve area and confusion matrix were employed. Results: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of

ABSTRACT Trade-offs between competitive ability and resistance to top-down control manifest the “kill-the-winner” hypothesis that explains how mortality caused by protists and viruses can promote bacterial diversity. However, the existence of such trade-offs has rarely been investigated in natural marine bacterial communities. To address this question, we conducted on-board dilution experiments to manipulate top-down control pressure (protists only or protists plus viruses [protists+viruses] combined) and then applied 16S rRNA gene high-throughput sequencing techniques to assess the responses of each bacterial taxon. Dilution experiments enabled us to measure the top-down-control-free growth rate as the competitive ability and top-down-control-caused mortality as the reverse of resistance to top-down control. Overall, bacterial taxa with higher top-down-control-free growth rates were accompanied by lower top-down-control-caused resistance. Furthermore, competition-resistance trade-offs were stronger and more consistent when top-down control was caused by protists+viruses combined than by protists only. When protists+viruses were diluted, the bacterial rank abundance distribution became steepened and evenness and richness were decreased. However, when protists were diluted, only richness decreased. Our results indicate the existence of competition-resistance trade-offs in marine microbes and demonstrate the positive impacts of such trade-offs on bacterial diversity. Regardless, the strength of the competition-resistance trade-offs and the impacts on bacterial diversity were contingent on whether top-down control was caused by protists+viruses combined or protists only. IMPORTANCE We addressed the “kill-the-winner” hypothesis from the perspective of its principle (the competition-resistance trade-off) in marine bacterial communities incubated in situ. Our results supported the existence of competition-resistance trade-offs and the positive effect on bacterial community diversity. The study linked theoretical expectations and complex natural systems and provided new knowledge regarding how top-down controls and competition trade-offs shaped natural bacterial communities.

Cells that cannot cope with persistent endoplasmic reticulum stress will die. Here, the authors show that iRhom pseudoproteases regulate cell death by modulating the ability of BCL-2 to inhibit calcium flow through IP3R channels.

Abstract Numerous supraglottic airway device (SADs) have been designed for adults; however, their relative efficacy, indicated by parameters such as adequacy of sealing, ease of application, and postinsertion complications, remains unclear. We conducted a systematic review and network meta-analysis to evaluate the efficacy of various SADs. We searched electronic databases for randomized controlled trials comparing at least two types of SADs published before December 2019. The primary outcomes were oropharyngeal leak pressure (OLP), risk of first-attempt insertion failure, and postoperative sore throat rate (POST). We included 108 studies (n = 10,645) comparing 17 types of SAD. The Proseal laryngeal mask airway (LMA), the I-gel supraglottic airway, the Supreme LMA, the Streamlined Liner of the Pharynx Airway, the SoftSeal, the Cobra Perilaryngeal Airway, the Air-Q, the Laryngeal Tube, the Laryngeal Tube Suction II, the Laryngeal Tube Suction Disposable, AuraGain, and Protector had significantly higher OLP (mean difference ranging from 3.98 to 9.18 cmH2O) compared with that of a classic LMA (C-LMA). The Protector exhibited the highest OLP and was ranked first. All SADs had a similar likelihood of first-attempt insertion failure and POST compared with the C-LMA. Our findings indicate that the Protector may be the best SAD because it has the highest OLP. Systematic review registration PROSPERO: CRD42017065273.

BackgroundHeart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are indices of cardiac autonomic and cardiac vagal control (CVC), both of which are markers of emotional regulation and physical health. This study examined (1) the differences in cardiac autonomic regulation and CVC during baseline, depressive, and happiness autobiographical memory tasks between participants with major depressive disorder (MDD group) and healthy controls (HC group); (2) the associations between depressive symptoms and cardiac autonomic and CVC; and (3) the reactivity and recovery of cardiac autonomic and CVC between the MDD and HC groups.MethodsA total of 168 and 178 participants were included in the MDD and HC groups, respectively. Demographic data and the Beck Depression Inventory-II were collected before the experimental procedure. Lead II electrocardiograph (ECG) was measured during baseline, depressive, and happiness autobiographical memory tasks, and then interbeat intervals from ECG were converted to the time and frequency domains of HRV and RSA.ResultsThe participants in the MDD group showed lower HRV (including standard deviation of normal to normal intervals, low frequency, the natural logarithm of low frequency, and the natural logarithm of high frequency) and CVC (RSA and lnRSA) than those in the HC group. Depressive symptoms were positively correlated with heart rate and negatively correlated with the indices of cardiac autonomic and CVC. There was significantly increased reactivity and recovery of cardiac autonomic and CVC during and after depressive and happiness autobiographical memory tasks in the HC group, but not in the MDD group.DiscussionParticipants with MDD had cardiac autonomic and CVC dysregulation, decreased reactivity, and did not recover to baseline after emotional provocations. These results can be the theoretical basis for clinical intervention by using HRV biofeedback to restore cardiac autonomic regulation and CVC during and after emotional events in the future.

Extracellular matrix (ECM) scaffolds are extensively used in tissue engineering studies and numerous clinical applications for tissue and organ reconstructions. Due to the global severe shortage of human tissues and organs, xenogeneic biomaterials are a common source for human tissue engineering and regenerative medicine applications. Traditional methods for decellularization often disrupt the 3D architecture and damage the structural integrity of the ECM scaffold. To efficiently obtain natural ECM scaffolds from animal tissues and organs with intact architecture, we have developed a platform decellularization process using supercritical CO2 and tested its potential application in tissue engineering. A combination of human mesenchymal stem cells with a decellularized dermal matrix scaffold allowed complete regeneration of skin structure in a porcine full-thickness wound model.

Background: Primary intestinal lymphomas (PILs) are rare, and this study compared the clinical outcomes of aggressive primary intestinal B-cell lymphomas (aB-PILs) and T/natural killer-cell lymphomas (T/NK-PILs). Methods: The clinical information of patients diagnosed with aggressive PILs at our institution between 1995 and 2015 were retrospectively investigated. Pathological subtypes were confirmed according to the 2016 revision of the World Health Organization classification. The correlation between clinicopathological features and overall survival (OS) was determined using univariate and multivariate analyses. Results: Cases of T/NK-PILs had higher initial bowel perforation incidence (67% vs. 7%, P

Background: Pseudomonas aeruginosa and nontyphoidal Salmonella (NTS) species may cause enteric illness with sepsis in infancy. The clinical predictors distinguishing the two pathogens have not been comprehensively evaluated in this population in Taiwan. Methods: A retrospective matched case–control study was conducted in a teaching hospital in southern Taiwan from January 1, 2003 to January 30, 2019. The patients with community-acquired P. aeruginosa sepsis were matched at a ratio of 1:2 by age and gender with controls (who developed NTS sepsis). Results: A total of 21 infants with community-acquired P. aeruginosa sepsis were identified; of these, 12 (57.1%) were male, and the mean ± standard deviation of age was 6.95 ± 2.47 months. Two independent predictors indicative of P. aeruginosa sepsis, as identified by multivariate analysis using conditional logistic regression, were hemoglobin level (Hb) (matched odds ratio [mOR], 0.155; 95% confidence interval [CI], 0.027–0.900; p = 0.038) and platelet count (mOR, 0.988, 95% CI, 0.976–1.000; p = 0.049). The areas under the receiver operating characteristic (ROC) curves of Hb and platelet count for P. aeruginosa sepsis prediction were 0.855 and 0.803, respectively. With cut-off values for Hb of 10.7 g/dL and platelet count of 173,000/μL, the predictors had maximal diagnostic accuracy. Conclusion: Most patients with P. aeruginosa sepsis are less than one year old. A lower hemoglobin level and a lower platelet count are significant predictors of P. aeruginosa sepsis. These findings should help to reshape the policy of empirical antibiotics in infants with sepsis.

Abstract Background The risk of tuberculosis (TB) in patients with impaired kidney function remains unclear by different stages of renal function impairment. Methods We retrospectively recruited all patients with kidney function in a tertiary-care referral center from January 2008 to December 2013 and followed them till December 2016. We defined the primary outcome as active TB development and analyzed the impact of kidney function impairment. Results During the study period, a total of 289,579 patients were enrolled for analysis, and of them, 1012 patients had active TB events in an average of 4.13 years of follow-up. According to kidney function impairment, the incidence rate of TB was similar in patients with no chronic kidney disease (CKD) or stage 1 and stage 2, and it increased apparently at stage 3a (167.68 per 100,000 person-years) to stage 3b, stage 4 and stage 5 (229.25, 304.95 and 349.29 per 100,000 person-years, respectively). In a Cox proportional hazard regression model, the dose response of TB risk among different stages of kidney function impairment increased significantly from CKD stage 3a to stage 5. Patients with long-term dialysis had a hazard ratio of 2.041 (1.092–3.815, p = 0.0254), which is similar to that of stage 4 CKD but lower than that of stage 5. Conclusion In patients with impaired kidney function, the risk of TB increases from CKD stage 3, and in stage 5, the risk is even higher than that of those receiving dialysis. Further strategies of TB control need to consider this high-risk group.

Background: Community-acquired Gram-Negative (GN) bacteremia caused more morbidity and mortality recently in children. The increasing drug resistance was also an important issue. However, published reference was few about children. Methods: We conducted a retrospective study to collect febrile patients with blood culture from a pediatric emergency department during 2007∼2013, and exclude cases ever admitted to hospital within 14 days. These blood cultures all showed single GN organism. The demographic characteristics of enrolled patients and the antibiogram of pathogens were recorded, and then were compared statistically to find out the immediate and appropriate antibiotics. Results: Total 143 sets of blood culture were GN bacilli and the median age of cases was 2 (IQR, 1-5) years old. Male gender was predominant. Non-fermenting Gram-negative bacilli group (NFGNB spp.), Salmonella spp. and Escherichia coli were first three common pathogens respectively. However, total 37 cases of NFGNB spp. other than Pseudomonas aeruginosa were the possible pathogens. By multiple logistic regression analysis, lower hemoglobin and higher alanine aminotransferase were significant difference between common pathogens and possible ones. Besides, the prevalent age regarding resistant strains of Escherichia coli and Pseudomonas aeruginosa were both focused on less than 1 year old. However, Salmonella spp. were prevalent in the age from 1 to 3 years old. Conclusions: For different age groups, Salmonella spp. and Escherchia coli were the most common pathogens of community-acquired GN bacteremia. For infants, Pseudomonas aeruginosa sepsis and resistant strain of Escherchia coli should be alert, and broader antibiotics should be considered. Key Words: community-acquired, bacteremia, gram-negative bacilli, infants

BackgroundAlthough carotid sonographic features have been used as predictors of recurrent stroke, few large-scale studies have explored the use of machine learning analysis of carotid sonographic features for the prediction of recurrent stroke.MethodsWe retrospectively collected electronic medical records of enrolled patients from the data warehouse of China Medical University Hospital, a tertiary medical center in central Taiwan, from January 2012 to November 2018. We included patients who underwent a documented carotid ultrasound within 30 days of experiencing an acute first stroke during the study period. We classified these participants into two groups: those with non-recurrent stroke (those who has not been diagnosed with acute stroke again during the study period) and those with recurrent stoke (those who has been diagnosed with acute stroke during the study period). A total of 1,235 carotid sonographic parameters were analyzed. Data on the patients' demographic characteristics and comorbidities were also collected. Python 3.7 was used as the programming language, and the scikit-learn toolkit was used to complete the derivation and verification of the machine learning methods.ResultsIn total, 2,411 patients were enrolled in this study, of whom 1,896 and 515 had non-recurrent and recurrent stroke, respectively. After extraction, 43 features of carotid sonography (36 carotid sonographic parameters and seven transcranial color Doppler sonographic parameter) were analyzed. For predicting recurrent stroke, CatBoost achieved the highest area under the curve (0.844, CIs 95% 0.824–0.868), followed by the Light Gradient Boosting Machine (0.832, CIs 95% 0.813–0.851), random forest (0.819, CIs 95% 0.802–0.846), support-vector machine (0.759, CIs 95% 0.739–0.781), logistic regression (0.781, CIs 95% 0.764–0.800), and decision tree (0.735, CIs 95% 0.717–0.755) models.ConclusionWhen using the CatBoost model, the top three features for predicting recurrent stroke were determined to be the use of anticoagulation medications, the use of NSAID medications, and the resistive index of the left subclavian artery. The CatBoost model demonstrated efficiency and achieved optimal performance in the predictive classification of non-recurrent and recurrent stroke.

Abstract Background Current guidelines have unsatisfied performance in predicting severe outcomes after Clostridium difficile infection (CDI). Our objectives were to develop a risk prediction model for 30-day mortality and to examine its performance among inpatients with CDI. Methods This retrospective cohort study was conducted at China Medical University Hospital, a 2111-bed tertiary medical center in central Taiwan. We included adult inpatients who had a first positive C. difficile culture or toxin assay and had diarrhea as the study population. The main exposure of interest was the biochemical profiles of white blood cell count, serum creatinine (SCr), estimated glomerular filtration rate, blood urea nitrogen (BUN), serum albumin, and glucose. The primary outcome was the 30-day all-cause mortality and the secondary outcome was the length of stay in the intensive care units (ICU) following CDI. A multivariable Cox model and a logistic regression model were developed using clinically relevant and statistically significant variables for 30-day mortality and for length of ICU stay, respectively. A risk scoring system was established by standardizing the coefficients. We compared the performance of our models and the guidelines. Results Of 401 patients, 23.4% died within 30 days. In the multivariable model, malignancy (hazard ratio [HR] = 1.95), ≥ 1.5-fold rise in SCr (HR = 2.27), BUN-to-SCr ratio > 20 (HR = 2.04), and increased glucose (≥ 193 vs 20 (Odds ratio [OR] = 4.01) was the only significant predictor for prolonged (> 9 days) length of ICU stay following CDI. The Harrell’s c statistic of our Cox model for 30-day mortality (0.727) was significantly superior to those of SHEA-IDSA 2010 (0.645), SHEA-IDSA 2018 (0.591), and ECSMID (0.650). Similarly, the conventional c statistic of our logistic regression model for prolonged ICU stay (0.737) was significantly superior to that of the guidelines (SHEA-IDSA 2010, c = 0.600; SHEA-IDSA 2018, c = 0.634; ESCMID, c = 0.645). Our risk prediction scoring system for 30-day mortality correctly reclassified 20.7, 32.1, and 47.9% of patients, respectively. Conclusions Our model that included novel biomarkers of BUN-to-SCr ratio and glucose have a higher predictive performance of 30-day mortality and prolonged ICU stay following CDI than do the guidelines.

Background: A regional antibiotic susceptibility database of certain pathogens is crucial for first-line physicians in terms of providing clinical judgement and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiological data of Salmonella serogroups and drug resistance in pediatric patients. Methods: This is a single-center retrospective study enrolling patients aged from 0 to 18 years who were hospitalized with cultured proven non-typhoidal Salmonella (NTS) infection from 2004 to 2019. The isolates were collected and the demographic data, serogroups of Salmonella and antimicrobial susceptibilities were further analyzed. Results: A total of 1583 isolates of NTS were collected. Serogroup C2 was prone to cause invasive non-typhoidal salmonellosis (iNTS), especially bacteremia. Patients aged < 2 years were associated with serogroups B and C2 infection, while those aged ≥ 2 years were associated with serogroups D and E infection. The prevalence of serogroup B declined with simultaneous increase in prevalence of serogroups D and E. Serogroups B and E were associated with ceftriaxone resistance, while Serogroup D was less drug-resistant than the others. The prevalence of ceftriaxone-resistant Salmonella had not increased, although more ciprofloxacin-resistant isolates were found in iNTS infection. Conclusions: Age < 2 years is a risk factor of iNTS for children, and the distribution of serogroup changes should be closely monitored. Ceftriaxone is still the drug of choice for treating pediatric iNTS infection, and although no increase was observed in the prevalence of ceftriaxone-resistant strains in this study, continuing surveillance of such cases is warranted.

Abstract Background H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P

Deep sequencing of T-cell receptor (TCR) genes is powerful at profiling immune repertoire. To prepare a TCR sequencing library, multiplex polymerase chain reaction (mPCR) is widely applied and is highly efficient. That is, most mPCR products contain the region critical for antigen recognition, which also indicates regular V(D)J recombination. Multiplex PCR, however, may suffer from primer bias. A promising alternative is 5'-RACE, which avoids primer bias by applying only one primer pair. In 5'-RACE data, however, non-regular V(D)J recombination (e.g., TCR sequences without a V gene segment) has been observed and the frequency varies (30-80%) between studies. This suggests that the cause of or how to reduce non-regular TCR sequences is not yet well known by the science community. Although it is possible to speculate the cause by comparing the 5'-RACE protocols, careful experimental confirmation is needed and such a systematic study is still not available. Here, we examined the 5'-RACE protocol of a commercial kit and demonstrated how a modification increased the fraction of regular TCR-β sequences to >85%. We also found a strong linear correlation between the fraction of short DNA fragments and the percentage of non-regular TCR-β sequences, indicating that the presence of short DNA fragments in the library was the main cause of non-regular TCR-β sequences. Therefore, thorough removal of short DNA fragments from a 5'-RACE library is the key to high data efficiency. We highly recommend conducting a fragment length analysis before sequencing, and the fraction of short DNA fragments can be used to estimate the percentage of non-regular TCR sequences. As deep sequencing of TCR genes is still relatively expensive, good quality control should be valuable.

Abstract Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

Background: The differences in brain activity between patients with major depressive disorder (MDD) and healthy adults have been confirmed by functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG). The prefrontal lobe and posterior cingulate cortex (PCC) are related to emotional regulation in patients with MDD. However, the high cost and poor time resolution of fMRI and PET limit their clinical application. Recently, researchers have used high time resolution of standardized weighted low-resolution electromagnetic tomography (swLORETA) to investigate deep brain activity. This study aimed to convert raw EEG signals into swLORETA images and explore deep brain activity in patients with MDD and healthy adults. Methods: BrainMaster EEG equipment with a 19-channel EEG cap was used to collect resting EEG data with eyes closed for 5 min. NeuroGuide software was used to remove the EEG artifacts, and the swLORETA software was used to analyze 12,700 voxels of current source density (CSD) for 139 patients with MDD and co-morbid anxiety symptoms (mean age = 43.08, SD = 13.76; 28.78% were male) and 134 healthy adults (mean age = 40.60, SD = 13.52; 34.33% were male). Deep brain activity in the frontal lobe and PCC at different frequency bands was analyzed, including delta (1–4 Hz), theta (5–7 Hz), alpha (8–11 Hz), beta (12–24 Hz), beta1 (12–14 Hz), beta2 (15–17 Hz), beta3 (18–24 Hz), and high beta (25–29 Hz). Results: There was lower delta and theta and higher beta, beta1, beta2, beta3, and high-beta activity at the prefrontal lobe (dorsal medial prefrontal cortex [dmPFC], ventral medial prefrontal cortex [vmPFC], and dorsal lateral prefrontal cortex [dlPFC], ventral lateral prefrontal cortex [vlPFC], orbital frontal cortex [OFC]) and PCC in MDD patients compared with healthy adults. There was no significant difference in alpha activity between the two groups. Conclusion: This study indicates brain hyperactivity in the right prefrontal lobe (dlPFC and vmPFC) and PCC in patients with MDD with co-morbid anxiety symptoms, and the dlPFC and PCC were also related to emotion regulation in MDD. Inhibiting high-beta activity or restoring delta and theta activity to the normal range in the right frontal lobe and PCC may be possible in z-score neurofeedback protocols for patients with MDD in future studies.

Abstract Prior cross-sectional analyses have demonstrated an association between subclinical hypothyroidism and metabolic syndrome and selected components. However, the temporal relation between metabolic syndrome and declining thyroid function remains unclear. In a prospective study, an unselected cohort of 66,822 participants with and without metabolic syndrome were followed. A proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs for hypothyroidism. Exploratory analyses for the relation between components of metabolic syndrome and declining thyroid function were also undertaken. During an average follow-up of 4.2 years, the incident rates for subclinical hypothyroidism were substantially higher in participants who began the study with metabolic syndrome compared with metabolically normal controls. After controlling for risk factors, patients with metabolic syndrome were at a 21% excess risk of developing subclinical hypothyroidism (adjusted HR 1.21; 95% CI 1.03–1.42). When individual components were analyzed, an increased risk of subclinical hypothyroidism was associated with high blood pressure (1.24; 1.04–1.48) and high serum triglycerides (1.18; 1.00–1.39), with a trend of increasing risk as participants had additional more components. Individuals with metabolic syndrome are at a greater risk for developing subclinical hypothyroidism, while its mechanisms and temporal consequences of this observation remain to be determined.

Background: Metoclopramide is used to relieve gastrointestinal symptoms, however, it could cause adverse reactions of motor disorders. The aim of this study was to investigate whether metoclopramide treatment has a duration–response or dose–response effect and to estimate the risk of developing Parkinsonism following different and specific durations of treatment. Methods: A cohort study of newly diagnosed type 2 diabetes mellitus in 45- to 79-year-old patients, between 1999 and 2008, was selected using the Longitudinal Health Insurance Database 2005. A nested case–control study was conducted in the diabetes cohort in which all incident cases of Parkinsonism were identified. We randomly matched each case with up to 10 controls from the risk set. Conditional logistic regression was utilized to estimate odds ratio of Parkinsonism associated with metoclopramide use. Results: A total of 34,685 patients with diabetes were assembled as the cohort, and 541 incident Parkinsonism cases were identified. There were duration–response and dose–response effects on the risk of developing Parkinsonism. Compared with never-use patients, the adjusted odds ratios (ORs) of continuing therapy for 0–1 month, 1–2 months, 2–3 months, 3–5 months, and more than 5 months were 1.17 [95% confidence interval (CI) 0.93–1.45], 1.44 (95% CI 1.04–2.00), 1.74 (95% CI 1.14–2.65), 1.90 (95% CI 1.23–2.93), and 2.17 (95% CI 1.50–3.12), respectively. Conclusions: With metoclopramide treatment, regardless of less or more than 3 months of use, the risk of developing Parkinsonism in patients with newly diagnosed diabetes escalated with the duration of therapy. Therefore, we recommend close monitoring for the development of Parkinsonism in patients treated with metoclopramide, particularly (but not limited to) those with prolonged exposure.

BackgroundDepression is common in dialysis patients, but the clinical impact of this condition is poorly defined.MethodsOut of 57,703 patients starting dialysis during 2000-2007 recorded in the National Health Insurance Research Database of Taiwan, we identified 2,475 patients with a clinical diagnosis of depression, and compared them with 1:5 age- and sex-matched patients without a depression diagnosis (n = 12,375). Patients were followed up for hospitalisation due to severe infections, major adverse cardiovascular events (MACE) and death. Multivariable Cox regression and competing risk analyses (accounting for death when appropriate) were used to estimate risk associations.ResultsPatients with depression had a higher frequency of comorbidities. During a mean follow-up of 3.2 years, 1,140 severe infections, 806 MACE, and 1,121 deaths were recorded. Compared to controls, patients with depression were at increased risk of death (adjusted hazard ratio 1.24; 95%CI 1.16-1.33). Patients with depression were also at higher risk of severe (1.14; 1.06-1.22) and fatal infections (death within 30 days, 1.22; 1.09-1.35), attributed mainly to sepsis (1.19; 1.08-1.31), septic shock (1.36; 1.13-1.62) and pneumonia (1.19; 1.07-1.33). Conversely, no association was observed between depression and the MACE risk (1.04; 0.94-1.15).ConclusionDialysis patients with depression are associated with increased risk of infections and death.

Objective To verify self-reported basic and instrumental activities of daily living (IADL) with a disability and the results of performance-based tests (namely the Taiwan performance-based IADL (TPIADL), the 2-minute step test (2MST), the 30-second chair-stand test (30-s CST), and handgrip dynamometer measurement) to identify disability early and assess the associations with functional fitness in patients with advanced chronic kidney disease (CKD). Methods A cross-sectional study of 99 patients with stage 4–5 CKD and 57 healthy elderly adults were recruited. Self-reported measures were used to collect information on basic (Barthel Index) and IADL (Lawton–Brody scale). Objective measures of the TPIADL and functional fitness (2MST, 30-s CST, handgrip dynamometer) were also assessed. Results Only IADL, as detected by the TPIADL, were impaired to a greater extent in the CKD patients than those of healthy elderly adults. Among all the patients with CKD, a greater impairment in the TPIADL remained statistically associated with a lower ability in the 2MST. A one step increase in the 2MST score was significantly associated with an improvement of 0.2 s in the total performance time of the TPIADL. Conclusion Performance-based measures, such as the TPIADL, may detect a functional limitation before it becomes measurable by traditional self-reported basic and IADL scales; functional limitation is mainly associated with cardiac endurance for advanced CKD.

ABSTRACT Mock communities have been used in microbiome method development to help estimate biases introduced in PCR amplification and sequencing and to optimize pipeline outputs. Nevertheless, the strong value of routine mock community analysis beyond initial method development is rarely, if ever, considered. Here we report that our routine use of mock communities as internal standards allowed us to discover highly aberrant and strong biases in the relative proportions of multiple taxa in a single Illumina HiSeqPE250 run. In this run, an important archaeal taxon virtually disappeared from all samples, and other mock community taxa showed >2-fold high or low abundance, whereas a rerun of those identical amplicons (from the same reaction tubes) on a different date yielded “normal” results. Although obvious from the strange mock community results, we could have easily missed the problem had we not used the mock communities because of natural variation of microbiomes at our site. The “normal” results were validated over four MiSeqPE300 runs and three HiSeqPE250 runs, and run-to-run variation was usually low. While validating these “normal” results, we also discovered that some mock microbial taxa had relatively modest, but consistent, differences between sequencing platforms. We strongly advise the use of mock communities in every sequencing run to distinguish potentially serious aberrations from natural variations. The mock communities should have more than just a few members and ideally at least partly represent the samples being analyzed to detect problems that show up only in some taxa and also to help validate clustering. IMPORTANCE Despite the routine use of standards and blanks in virtually all chemical or physical assays and most biological studies (a kind of “control”), microbiome analysis has traditionally lacked such standards. Here we show that unexpected problems of unknown origin can occur in such sequencing runs and yield completely incorrect results that would not necessarily be detected without the use of standards. Assuming that the microbiome sequencing analysis works properly every time risks serious errors that can be detected by the use of mock communities.

BACKGROUND:Our previous study demonstrated that pediatricians prescribe antibiotics without proper clinical justification to patients with enterovirus infection, although antibiotics are not effective in treating the infections caused by these viruses. To improve the quality of healthcare, we aim to evaluate the association of clinical and demographic characteristics of patients and further to identify the determining factors for prescribing antibiotics to children experiencing enterovirus infection. METHODS:We retrospectively reviewed the medical records of children who were hospitalized between January 2008 and December 2016 with a diagnosis of herpangina or hand-foot-mouth disease (HFMD). We identified those children who were prescribed antibiotics for at least 24 hours during admission. We conducted a retrospective descriptive study to analyze data in order to determine the factors associated with pediatrician antibiotics prescribing for enterovirus infection. RESULTS:In the nine years of study period, the rate of antibiotics use was about 13% in these patients. A total of 3659 patients were enrolled during 2008~2012 and analyzed in detail. Elevated levels of C-reactive protein (CRP) and presence of leukocytosis in blood (WBC) were both significantly associated with pediatrician antibiotic prescribing for enterovirus infection (p

One of the main objectives behind the expansion of insurance coverage is to eliminate disparities in health and healthcare. However, researchers have not yet fully elucidated the reasons for disparities in the use of high-cost treatments among patients of different occupations. Furthermore, it remains unknown whether discretionary decisions made at the hospital level have an impact on the administration of high-cost interventions in a universal healthcare system. This study investigated the adoption of drug-eluting stents (DES) versus bare metal-stents (BMS) among patients in different occupations and income levels, with the aim of gauging the degree to which the inclination of health providers toward treatment options could affect treatment choices at the patient-level within a universal healthcare system.We adopted a cross-sectional observational study design using hierarchical modeling in conjunction with the population-based National Health Insurance database of Taiwan. Patients who received either a BMS or a DES between 2007 and 2010 were included in the study.During the period of study, 42,124 patients received a BMS (65.3%) and 22,376 received DES (34.7%). Patients who were physicians or the family members of physicians were far more likely to receive DES (OR: 3.18, CI: 2.38-4.23) than were patients who were neither physicians nor in other high-status jobs (employers, other medical professions, or public service). Similarly, patients in the top 5% income bracket had a higher probability of receiving a DES (OR: 2.23, CI: 2.06-2.47, p < .001), than were patients in the lowest income bracket. After controlling for patient-level factors, the inclination of hospitals (proportion of DES>50% or between 25% and 50%) was shown to be strongly associated with the selection of DESs (OR: 3.64 CI: 3.24-4.09 and OR: 2.16, CI: 2.01-2.33, respectively).Even under the universal healthcare system in Taiwan, socioeconomic disparities in the use of high-cost services remain widespread. Differences in the care received by patients of lower socioeconomic status may be due to the discretionary decisions of healthcare providers.

Tyrosinase, chitosan, and reduced graphene oxide (rGO) are sequentially used to modify a screen-printed carbon electrode (SPCE) for the detection of dopamine (DA), without interference from uric acid (UA) or ascorbic acid (AA). The use of tyrosinase significantly improves the detection’s specificity. Cyclic voltammetry (CV) measurements demonstrate the high sensitivity and selectivity of the proposed electrochemical sensors, with detection limits of 22 nM and broad linear ranges of 0.4⁻8 μM and 40⁻500 μM. The fabricated tyrosinase/chitosan/rGO/SPCE electrodes achieve satisfactory results when applied to human urine samples, thereby demonstrating their feasibility for analyzing DA in physiological samples.

The aims of this study were (1) to examine differences in the level of self-esteem among adolescents with different roles in aggression involvement (aggression perpetrators, victims, perpetrator-victims and neutrals) according to gender and (2) to examine the moderating effects of depression and family support on association between aggression involvement and self-esteem. A total of 8085 adolescents in Taiwan completed questionnaires. The relationships between self-esteem and aggression involvement were examined by multiple regression analysis. The moderating effects of depression and family support on the association between aggression involvement and self-esteem were examined. The results showed that in females, aggression victims had lower self-esteem than those in the other three groups (t=−2.940 to 2.173, p0.05). In males, self-esteem in victims and perpetrator-victims was lower than in neutrals and perpetrators (t=−3.339 to −2.704, p0.05) or between perpetrators and neutrals (t=−1.396, p>0.05). Family support had a moderating effect on the association between self-esteem and victimization in males. Depression had a moderating effect on the association between self-esteem and perpetration-victimization and victimization in males. The results indicate that self-esteem in adolescents with different patterns of involvement in aggression is not the same as in those without involvement. The moderating effects of depression and family support should be considered when developing intervention strategies to raise self-esteem in adolescents with aggression involvement.

To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI) in Mandarin-speaking subjects and to investigate the clinical application of the shortest form.Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC) analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening.Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control group in the three neuropsychological protocols. Forty-two patients with stroke were diagnosed with VCI. VCI was used as the standard to estimate the criteria validities. The area under the ROC curve was 0.78, 0.80, 0.75, and 0.73 for the 60-, 30-, 5-mintue protocol-A and 5-minute protocol-B, respectively.These modified neuropsychological protocols can be used as valid instruments when performing comprehensive cognitive assessment or for screening of VCI in Taiwan.

Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants' reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy.Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined.Cronbach's alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = -0.587, p

Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients.This cross-sectional study enrolled 172 of CKD stages 1-5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status (extracellular water/total body water, ECW/TBW), lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method.All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P

This study aims to examine the prevalence and sociodemographics, family and peer correlates of tattooing among high school students in southern Taiwan, and to examine the associations between tattooing and a variety of adolescent risk-taking behaviors and depression. A total of 9755 high school students (grades 7 to 12) in southern Taiwan were recruited into this study and completed the questionnaires. The prevalence of tattooing among the adolescents was calculated. The responses were analyzed using the logistic regression analysis models. It was found that 1% of high school students in southern Taiwan had 1 or more tattoos on their bodies. The older students who were perceived to have low family monitoring and who had friends who drink regularly, used illicit drugs, had a criminal record or were in a gang were more likely to have a tattoo. Tattooing was also found to be associated with violence, weekly alcohol consumption, illicit drug use, dropping out of school, unprotected sex, suicidal ideation/attempt, and depression. The results indicate that several demographics, family and peer factors are associated with adolescent tattooing. Tattooing may be an indicator of risk-taking behaviors in high school students.

The development of an instrument to estimate the incidence, characteristics, and risk factors of benzodiazepine (BZD) dependence broadly in Taiwan is an important task. This study assessed the validity of the Chinese version of the Severity of Dependence Scale (SDS[Ch]) among regular BZD users in Taiwan (n=228). A positive correlation was shown between SDS[Ch] and Mini-International Neuropsychiatric Interview diagnosed of BZD dependence. Thirty-six percent of the users received a Mini-International Neuropsychiatric Interview diagnosis of current BZD dependence. The dependent users tended to be divorced/widowed; not schizophrenic; and have higher SDS[Ch] scores, a longer duration of use, and multiple-BZD use. The SDS[Ch] for BZD dependence was shown to have high diagnostic utility (area under the receiver operating characteristic curve=0.779), a sensitivity of 80.5%, and a specificity of 85.7%, with a cutoff point of 7. The findings support that the SDS[Ch] is a valid brief self-reported questionnaire for the assessment of BZD dependence among chronic users in Taiwan.

Behavioral and psychological symptoms of dementia (BPSD) are common and debilitating problems, but current treatments are limited. Antipsychotic agents show some efficacy on BPSD, but their use is limited by the associated risk of cerebrovascular events and mortality. Reports have shown the efficacy of mood stabilizers on BPSD, but systemic reviews on this issue are scant. This article aims to review studies of the efficacy of mood stabilizers on BPSD, and the quality of the available evidence. We searched for articles published in English during the period 1990 to 2010 and included in the PubMed database that concerned treatment of BPSD with mood stabilizers, such as carbamazepine, valproate, gabapentin, topiramate, lamotrigine, oxcarbazepine and lithium. The quality of the studies was assessed by considering the trial designs, analyses, subjects and results. We found one meta-analysis and three randomized controlled trials (RCTs) supporting the efficacy of carbamazepine in managing global BPSD, particularly aggression and hostility. With regard to valproate, current evidence from one meta-analysis and five RCTs did not strongly support its efficacy for global BPSD, including agitation and aggression. Only open trials or case series showed some efficacy of gabapentin, topiramate and lamotrigine in controlling BPSD. The single RCT investigating the effect of oxcarbazepine on agitation and aggression showed negative results. Case series reports on lithium tended to show it to be ineffective. Thus far, among mood stabilizers, carbamazepine has the most robust evidence of efficacy on BPSD. More RCTs are needed to strengthen evidence regarding the efficacy of gabapentin, topiramate and lamotrigine. Valproate, oxcarbazepine and lithium showed low or no evidence of efficacy. Large and well designed RCTs focusing on specific symptoms of BPSD are needed to deal with the issue.

Kluver–Bucy syndrome (KBS) is a collection of neuropsychiatric symptoms, including visual agnosia (prosopagnosia), hypermetamorphosis, placidity, hypersexuality, and hyperorality. Although neuropsychiatric manifestation is prevalent in cases with systemic lupus erythematosus (SLE), only one literature reported a case with SLE that had KBS previously. In this article, a 37-year-old woman with SLE who developed KBS and other neuropsychiatric symptoms is presented. Brain imaging proved the relevant structural lesion. The possible explanation of pathogenesis of KBS in SLE is discussed.

The aims of this study were to examine unfavorable attitudes toward receiving methadone maintenance therapy (MMT) and associated factors among inmates using intravenous heroin in Taiwan. A total of 315 inmates using intravenous heroin were recruited. Their unfavorable attitudes toward receiving MMT after discharge from prison were evaluated using the Client Attitudes Toward Methadone Programs Scale. The associations of unfavorable attitudes toward receiving MMT with sociodemographic and drug-using characteristics, human immunodeficiency virus serostatus, perceived family support, and depression were examined using multiple regression analysis. The results of this study showed that the mean score of unfavorable attitudes toward receiving MMT, determined on the Client Attitudes Toward Methadone Programs Scale, was 9.918 (standard deviation=2.277, range=5–20). Heroin-using inmates who were young, started using heroin earlier, perceived many advantages and few disadvantages of heroin use, had never received MMT, and had severe depression, had unfavorable attitudes toward receiving MMT. Based on the results of this study, we suggest that inmates who have the factors associated with unfavorable attitudes toward receiving MMT should receive intervention and motivational interviewing to improve their attitudes toward MMT and to increase their opportunity to receive MMT after discharge from prison.

Caregivers of patients with late-life major depressive disorder experience a significant level of general caregiver burden. Disability in patients is possibly one of the origins of caregiver burden. Frontal lobe dysfunction might be the source of disability. This study investigated if frontal lobe dysfunction (body level) of patients with late-life major depressive disorder was associated with their disability (individual level), and if it led to a high level of caregiver burden (societal level). Thirty-four unselected pairs of caregivers and their family members with late-life major depressive disorder were recruited. Frontal Assessment Battery and Timed Instrumental Activities of Daily Living (TIADL) were used to assess patients' frontal function and disability, and Caregiver Burden Inventory was used to measure caregiver burden. Frontal Assessment Battery correlated with TIADL (r= −0.47; p

Body dysmorphic disorder (BDD) refers to a preoccupation with an imagined or grossly exaggerated minor physical defect. Those with BDD might seek medical help (cosmetic surgery) rather than attend a psychiatric clinic. Therefore, it is often underdiagnosed. To investigate the prevalence of BDD, we reviewed the medical records of 817 individuals who sought cosmetic surgery during a 3-year period. The outcome after surgery was described for those with BDD. Our results showed that 63 (7.7%) patients had BDD, of which 54 (85.7%) were diagnosed at preoperative evaluation. However, nine (14.3%) patients went undiagnosed and all had a bad outcome after cosmetic surgery. BDD was not uncommon at the cosmetic surgery clinic. Our results support the idea that cosmetic surgery should be avoided for patients with BDD. The development of a more effective diagnostic procedure could help address this issue.

The care of patients with obsessive-compulsive disorder (OCD) has raised quality of life (QOL) issues. The purpose of this study was to compare the level of QOL between patients with and without OCD, and to examine the associations between QOL and sociodemographic data, course of illness, psychopathology, perceived social support, and treatment characteristics. The QOL levels measured with the Taiwan version of the Short Form of the World Health Organization Questionnaire on Quality of Life were compared between 57 subjects with OCD and 106 subjects without OCD. The correlates of QOL were examined among subjects with OCD. The analysis revealed that QOL scores for the general, physical, psychological and social relationship domains were lower in the OCD group than in the control group; however, no difference in the environmental domain was found. Multiple factors were associated with poor QOL in subjects with OCD, including comorbid depression, severe obsession symptoms, perceived low social support, severe adverse effects of medication, combined use of mood stabilizers, and low social status. Different domains of QOL are differently affected by OCD. The QOL of subjects with OCD was correlated to multiple factors that were specific to individual subjects and influenced by interactions with treatment and the social environment.

Alexithymia refers to a person's inability to identify and describe feelings. We present a patient who developed alexithymia after carbon monoxide poisoning following a suicide attempt by burning charcoal in an enclosed space. Brain computed tomography revealed bilateral globus pallidus hypoxic lesions. Because of the time frame and the presence of brain structural lesions, the alexithymia in this patient was thought to be caused by bilateral globus pallidus hypoxic lesions resulting from carbon monoxide poisoning. The alexithymia in this patient did not respond to a variety of psychotropic drugs, including sertraline, venalfaxine, bupropion or methylphenidate. We suggest that alexithymia, which was associated with brain hypoxic lesions in this case, is resistant to treatment.

The aim of this study was to analyze the association between substance use and body mass index (BMI) among adolescents in Southern Taiwan. A total of 10,259 adolescent students aged 11–19 years were selected by stratified random sampling for proportional representation of districts, schools and grades in Southern Taiwan, and completed the questionnaires. The body weight, body height, experience of substance use and sociodemographic characteristics including sex, age, residential background and paternal/maternal educational levels were collected. The association between substance use and BMI, and the moderating effects of sociodemographic characteristics were examined. After adjusting for sociodemographic characteristics, BMI was higher for adolescents who smoke cigarettes or drink alcohol than for those who do not regularly smoke or drink. Chewing betel nuts and using illicit drugs were not significantly associated with BMI. Paternal education level had a moderating effect on the association between smoking and BMI. Smoking, alcohol drinking, and low paternal education level were associated with higher BMI among adolescents. Thus, healthcare professionals should pay more attention to the weight-related problems among these adolescents.

This study aimed to examine the correlations between academic achievement and levels of anxiety and depression in medical students who were experiencing curriculum reform. The differences in academic achievement and the directions of correlations between academic achievement and anxiety and depression among the medical students with different levels of anxiety and depression were also examined. Grade 1 students from graduate-entry program and grade 3 students from undergraduate-entry program in their first semester of the new curriculum were recruited to complete the Zung's Anxiety and Depression Scale twice to examine their levels of anxiety and depression. Their academic achievement ratings in the four blocks of the first semester of the new curriculum were collected. The results indicated that no significant correlation was found between academic achievement and global anxiety and depression. However, by dividing the medical students into low, moderate and high level anxiety or depression groups, those who had poorer academic achievement in the first learning block were more likely to have higher levels of depression in the first psychologic assessment. Among the medical students who were in the high anxiety level group in the first psychologic assessment, those who had more severe anxiety had poorer academic achievement in the fourth learning block. Among the medical students who were in the low anxiety level group in the second psychologic assessment, those who had more severe anxiety had better academic achievement in the fourth learning block. Among the medical students who were in the moderate anxiety level group in the second psychologic assessment, those who had more severe anxiety had poorer academic achievement in the second learning block. Among the medical students who were in the high depression level group in the second psychologic assessment, those who had more severe depression had poorer academic achievement in the fourth learning block. The results of this study indicate that there are both positive and negative correlations between academic achievement and anxiety and depression in medical students, regarding differing levels of severity of anxiety or depression. The results could represent a reference for teachers on the planning of teaching and assessment programs.

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.

BACKGROUND: Limited information about tumor status and the time at which antiviral therapy was initiated may have influenced effect estimation in previous research. The aim of this study was to investigate the effect of antiviral therapies on HBV-related HCC progression and deaths in patients receiving curative treatment based on clear clinical-pathological cancer status and the association of start time of adjuvant antiviral therapy initiation and outcomes. METHODOLOGY: A nationwide inception cohort study of newly diagnosed HCC patients who suffered from viral hepatitis B and received curative HCC therapy as the first course of treatment were identified from the Taiwan Cancer Registry between January 1, 2004, and December 31, 2009. Matched Cox proportional hazards models based on propensity score matching and incorporated time-varying exposure were used to estimate adjusted hazard ratios and 95% confidence intervals (CIs). FINDINGS: Among 3,855 HCC patients with HBV, antiviral therapy was administered to 490 (12.7%) following curative treatment. Antiviral-treated patients had a higher percentage of young age, early stage, and smaller tumor size of HCC compared with untreated patients. After propensity score matching, treated patients demonstrated a higher risk of HCC progression (hazard ratio, 1.42; 95%CI, 1.20-1.69) and death from all causes (1.45; 1.15-1.82) than untreated patients. Similar results were also obtained in sub-cohort of patients who were alive with cancer-free status at least one year after receiving curative treatment and the sub-cohort of patients with liver resection. The interval length between initiation of antiviral therapy and first-line curative treatment did not show a significant association with all-cause mortality. CONCLUSIONS: This study found that adjuvant antiviral therapy did not reduce the risk of HCC progression or mortality in HBV-related HCC patients after cancer status adjusting.

BACKGROUND: Randomized trials suggest that radiofrequency ablation (RFA) may be more effective than percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC). However, the survival advantage of RFA needs confirmation in daily practice. METHODS: We conducted a population-based cohort study using the Taiwan Cancer Registry, National Health Insurance claim database and National Death Registry data from 2004 through 2009. Patients receiving PEI or RFA as first-line treatment for newly-diagnosed stage I-II HCC were enrolled. RESULTS: A total of 658 patients receiving RFA and 378 patients receiving PEI treatment were included for final analysis. The overall survival (OS) rates of patients in the RFA and PEI groups at 5-year were 55% and 42%, respectively (p < 0.01). Compared to patients that received PEI, those that received RFA had lower risks of overall mortality and first-line treatment failure (FTF), with adjusted hazard ratios (HRs) [95% confidence interval (CI)] of 0.60 (0.50-0.73) for OS and 0.54 (0.46-0.64) for FTF. The favorable outcomes for the RFA group were consistently significant for patients with tumors > 2 cm as well as for those with tumors < 2 cm. Consistent results were also observed in other subgroup analyses defined by gender, age, tumor stage, and co-morbidity status. CONCLUSION: RFA provides better survival benefits than PEI for patients with unresectable stage I-II HCC, irrespective of tumors > 2 cm or ≤ 2 cm, in contemporary clinical practice.

BACKGROUND/AIMS: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. METHODS: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. RESULTS: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p

The recent threats of influenza epidemics and pandemics have prioritized the development of a universal vaccine that offers protection against a wider variety of influenza infections. Here, we demonstrate a genetically modified virus-like particle (VLP) vaccine, referred to as H5M2eN1-VLP, that increased the antigenic content of NA and induced rapid recall of antibody against HA(2) after viral infection. As a result, H5M2eN1-VLP vaccination elicited a broad humoral immune response against multiple viral proteins and caused significant protection against homologous RG-14 (H5N1) and heterologous A/California/07/2009 H1N1 (CA/07) and A/PR/8/34 H1N1 (PR8) viral lethal challenges. Moreover, the N1-VLP (lacking HA) induced production of a strong NA antibody that also conferred significant cross protection against H5N1 and heterologous CA/07 but not PR8, suggesting the protection against N1-serotyped viruses can be extended from avian-origin to CA/07 strain isolated in humans, but not to evolutionally distant strains of human-derived. By comparative vaccine study of an HA-based VLP (H5N1-VLP) and NA-based VLPs, we found that H5N1-VLP vaccination induced specific and strong protective antibodies against the HA(1) subunit of H5, thus restricting the breadth of cross-protection. In summary, we present a feasible example of direction of VLP vaccine immunity toward NA and HA(2), which resulted in cross protection against both seasonal and pandemic influenza strains, that could form the basis for future design of a better universal vaccine.