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Parkinson's disease (PD) is an incapacitating neurodegenerative disease. Patients with PD and their caregivers may have interactive effects on each other’s psychological well-being. This study aimed to assess the dyadic dynamics of resilience, fatigue, and suicidal ideation on the depression severity of PD patients and their caregivers. In total, 175 PD patients and 175 caregivers were recruited at a medical center from August 2018 to May 2020. Structural equation modeling (SEM) was used to examine the actor/partner effects on the psychological well-being of both the PD patients and their caregivers. The most common psychiatric diagnoses of both the PD patients (28.6%) and their caregivers (11.4%) were depressive disorders. The PD patients’ and their caregivers’ fatigue, suicidal ideation, and lack of resilience were significantly associated with the severity of their depression, respectively. Interactive effects existed between psychological well-being of individuals with PD and their caregivers. Clinicians must be aware of, and manage, these contributing factors between PD patients and their caregivers in order to prevent them from worsening each other’s depression.

Decentralization mechanism provides manufacturers and distributors with greater customization and flexibility they need through IoT-based Industrial Collaboration Systems (IoT-ICS), but it has brought forward security concerns about the shared data-processing tasks and IoT-based access to services and resources. To address them, we propose a practical blockchain solution to achieve decentralized policy management and evaluation on Attribute-based Access Control (ABAC). By offloading the responsibility of ABAC policy administration and decision-making to blockchain nodes, a blockchain-based access control framework, called Policychain, is presented to ensure policy with high availability, autonomy, and traceability. To deliver a solid design, we first present a transaction-oriented policy expression scheme with a well-defined syntax and semantics. The scheme can translate ABAC policies into the blockchain transactions with JavaScript Object Notation (JSON) syntax and Script-based logical expression. We further realize a script-driven policy evaluation by extending blockchain inherent scripting instructions to support attribute acquisition of ABAC entities. Furthermore, we propose a policy lifecycle management scheme from policy creation, renovation, to revocation, in which policies are verified by three validation principles at the transaction level. Finally, we provide sophisticated analysis and experiments to show that our framework is secure and practical for decentralized policy management on ABAC in IoT-ICS.

Introduction Mammographic breast density (MBD) is a known risk factor for breast cancer and older women have higher incidence rates of breast cancer occurrence. The Breast Imaging Reporting and Data System (BI-RADS) is a commonly used MBD classification tool for mammogram reporting. However, they have limitations since there are reading inconsistencies between different radiologists with the visual assessment of breast density. Methods Digitised film-screen mammographic images were extracted from the Digital Database for Screening Mammography (DDSM). A machine learning project was developed using commercially available software with several predictive models applied to classify different amount of MBD on mammograms into different density groups. The effectiveness of different predictive models used in classifying the mammograms were tested by receiver operator characteristics (ROC) curve with comparison to the gold standard of BI-RADS classification. Results Three predictive models, Decision Tree (Tree), Support Vector Model (SVM) and k-Nearest Neighbour (kNN) showed high AUC values of 0.801, 0.805 and 0.810 respectively. High AUC values for the three predictive models indicates that the accuracy of the model is approaching that of the BI-RADS method. Discussion Our machine learning project showed to have capabilities to be potentially used in the clinical settings to help categorise mammograms into extremely dense breasts (BI-RADS Group A) from entirely fatty breasts (BI-RADS Group D). Conclusion Findings from the present study suggest that the machine learning method is potentially useful to quantify the amount of MBD in mammograms.

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.

Hypertension is a leading cause of death and disability in the United States and worldwide. As primary care clinicians, nurse practitioners help patients control their blood pressure through lifestyle coaching and medication. Among the first-line medications for hypertension are calcium channel blockers, such as amlodipine. In the US, over 70 million prescriptions for amlodipine are written annually. Here we present a case report of a significant adverse event due to the use of amlodipine—gingival overgrowth. We review the pathophysiology, prevalence, and clinical management of gingival overgrowth. We also expand the understanding of this phenomenon by exploring the serious health justice implications of this adverse effect. Unchecked, gingival overgrowth can lead to tooth movement and eventual loss. Dental changes also cause pain, financial hardship, and psychosocial damage. Patients in poverty are at much greater risk for this adverse outcome due to limited access to dental care. Black patients specifically face a triple threat with higher rates of hypertension and its complications, guidelines that limit therapeutic options for first-line treatment, and high rates of poverty limiting access to dental care.

This research compared the incidence of adjacent segment pathology (ASP) between anterior interbody lumbar fusion (ALIF) treatment and transforaminal lumbar interbody fusion (TLIF) treatment. Seventy patients were included in this retrospective study: 30 patients received ALIF treatment, and 40 patients received TLIF treatment at a single medical center between 2011 and 2020 with a follow-up of at least 12 months. The outcomes were radiographic adjacent segment pathology (RASP) and clinical adjacent segment pathology (CASP). The mean follow-up period was 42.10 ± 22.61 months in the ALIF group and 56.20 ± 29.91 months in the TLIF group. Following single-level lumbosacral fusion, ALIF is superior to TLIF in maintaining lumbar lordosis, whereas the risk of adjacent instability in the ALIF group is significantly higher. Regarding ASP, the incidence of overall RASP and CASP did not differ significantly between ALIF and TLIF groups.

Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3–6] versus 4[2–6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.

Background: In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy. Methods: In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy were excluded. Rates of and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed. Results: Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN: 69.5 [25–75% IQR: 62.8–77.3] vs. 64.0 [25–75% IQR: 61.0–68.0]; p < 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN: 94.5% vs. 76.5%; p < 0.05) and in BCLC stage B (DAA vs. IFN: 95.2% vs. 76.5%; p < 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI: 1.3–25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI: 1.1–12.9) were independent factors associated with SVR (all p < 0.05). Conclusions: Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

BACKGROUND Streptococcal toxic-shock syndrome after hemorrhoidectomy is rare but may be catastrophic. Group A streptococci have produced various surface proteins and exotoxins due to genetic changes to fight the human body’s immune response. Though life threatening infection after hemorrhoidectomy rarely occurs, all surgeons should be aware of the potential complications of severe sepsis after hemorrhoidectomy and keep in mind their clinical presenting features in order to diagnose early and administer appropriate and effective therapeutic drugs early. CASE SUMMARY Here, we present a case of a 56-year-old man with a painful thrombotic external hemorrhoid who presented to our outpatient department for management. There was no history of systemic diseases or recent disease infection. Hemorrhoidectomy was suggested and performed. After surgery, the patient developed hypotension, tachycardia, fever with chills and renal function impairment on day 2 post-operation. The clinical condition progressed to severe septic shock and metabolic acidosis. The patient responded poorly to treatment and expired after 1 d even with use of extracorporeal membrane oxygenation. The results of the blood and wound cultures showed group A streptococcus pyogenes. CONCLUSION Although extremely uncommon, all surgeons should be aware of these potential life-threatening septic complications and alert to the presenting features for patients receiving hemorrhoidectomy.

Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p, Final tumor grading of oral cavity squamous cell carcinoma (OCSCC) is assigned according to the most prevalent grade. Relapses of poorly differentiated OCSCC tended to occur regionally and distantly. Poor tumor differentiation was the second most relevant adverse risk factor after extranodal extension. The NCCN guidelines should include poor differentiation as an adverse risk factor.

Background We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. Methods A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score‐matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). Results Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3−4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5‐year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease‐free survival, 84%/83%/68%/52%; disease‐specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values 0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. Conclusions Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease., Patients with oral cavity squamous cell carcinoma and cN+pN0 disease are characterized by a higher prevalence of adverse risk factors. However, this was not found to translate into a less favorable prognosis; therefore, the presence of cN+pN0 disease should not be considered as an adverse prognostic factor

BACKGROUND AND AIM Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2 = 0.998) or frozen (R2 = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2 = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (β = 0.106, P = 0.033), lipase (β = 0.154, P = 0.007), and CA19-9 (β = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Context Individuals with diabetes mellitus (DM) are susceptible to various infections. Objective We estimated the risk of herpes zoster (HZ) among individuals with DM compared with individuals in the general population. Methods We searched the PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and PerioPath databases from their inception to January 30, 2021, for studies on the risk of HZ in individuals with DM. Two authors independently screened all articles identified. The same 2 authors independently extracted the data. Four case-control studies and 12 cohort studies were included. Results Meta-analyses were performed using fixed and mixed-effects models. In the pooled analysis, individuals with DM had a higher risk of developing HZ (pooled relative risk [RR]: 1.38; 95% CI, 1.21-1.57) than individuals in the general population. The results were consistent in subgroup analyses stratified by type of diabetes, age, and study design. In individuals with DM, cardiovascular disease had an additive effect on increasing the risk of HZ (pooled RR: 1.19; 95% CI, 1.11-1.28). There was a linear dose-response association between age and the risk of HZ in individuals with DM. Conclusion Individuals with DM have an increased risk of HZ compared with the general population. Varicella vaccination should be provided to individuals with DM regardless of their age, prioritizing older adults and those with cardiovascular disease. Varicella vaccination policies for individuals with DM should be updated based on the evidence.

Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients’ stigma, depression, and anxiety, and elucidate the underlying relationships among them. This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. Those patients having stressors of worry about health (t = 5.21, p

BACKGROUND Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive procedure for evaluating hilar and mediastinal lymph nodes. The reported sensitivity and specificity of EBUS-TBNA are 95% and 97%, respectively. A comparison of diagnostic sensitivity for lymph nodes suspected of lung cancer according to needle size in EBUS-TBNA is needed. OBJECTIVES To compare the diagnostic sensitivity of the 19-G, 21-G, 22-G and 25-G needles for lymph nodes suspected of non-small cell lung cancer (NSCLC) using EBUS-TBNA. METHODS A literature search from PubMed, EMBASE, LILACS, DOAJ and CENTRAL through October 2020 was performed by two reviewers. The extracted data were evaluated using STATA® and Open Meta Analyst software for meta-analysis with a binary method model to compare sensitivity, specificity and summary receiver operating characteristic curve for each needle size. RESULTS Fourteen studies including 1296 participants were considered for the analysis. The overall sensitivity of EBUS-TBNA was 88.2% (95% CI 84%, 91%) and 93% (95% CI 88%, 95%) for the 19-G needle, 87.6% (95% CI 79.6%, 92.8%) for the 21-G needle and 85% (95% CI 80%, 88%) for the 22-G needle. The overall sensitivity of EBUS-TBNA for diagnosing NSCLC was 88.3% (95% CI, 81%, 93%) and 92.9% (95% CI, 85%, 97%) for the 19-G needle, 89.4% (95% CI 79.4%, 94.8%) for the 21-G needle and 82.1% (95% CI 66%, 91%) for the 22-G needle. CONCLUSION The 19-G, 21-G and 22-G needles present a similarly high diagnostic sensitivity in EBUS-TBNA. The 19-G needle provided better sample adequacy for molecular and immunohistochemical testing, improving diagnostic yield in this subgroup.

In this study, quantum dot light-emitting diodes with a side-pumping structure were designed for efficient heat management. The COMSOL Multiphysics software suite was used to conduct numerical evaluations. The electrical and optical field distributions and the heat distribution capability of the aforementioned structure were investigated. The side-pumping package was found to be capable of effectively dissipating heat and significantly reducing the areal temperature from 32.1 °C (in-chip) to 28.9 °C with an operating current of 35 mA. The integrated intensities of the perovskite quantum dot photons of the in-chip and side-pumping devices were approximately identical (1.23:1). However, the side-pumping device required 58.3% less filling material than the in-chip device. Optical and thermal modeling and measurements indicated that the side-pumping architecture can not only enhance thermal dissipation but also reduce the usage of quantum dot material. The findings of this study provide useful information for the incorporation of quantum dots in photonic devices.

PURPOSE: To investigate the changes in tear neuromediators and corneal subbasal nerve plexus following small incision lenticule extraction (SMILE) and to study its association with different refractive power of corrections. METHODS: Thirty patients were included for tear neuromediator analysis (40 eyes) and corneal nerve analysis using in vivo confocal microscopy scans (20 eyes). Tear samples were collected preoperatively and 1 week and 1, 3, 6, and 12 months postoperatively and analyzed for the substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) concentrations using the enzyme-linked immunosor-bent assay (ELISA). RESULTS: Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) decreased significantly postoperatively, then gradually increased from 3 months onward, but did not recover to the baseline levels at 12 months. Tear substance P and CGRP levels remained stable over 12 months. Tear NGF levels demonstrated a small peak at 1 week before decreasing significantly compared to preoperative levels at 6 months ( P = .03) and 12 months ( P = .007). The 1-month reduction in CNFL, tear substance P, and CGRP concentrations were significantly correlated with the corrected spherical equivalent (SE) ( r = 0.71 for CNFL; r = −0.33 to −0.52 at different time points for substance P and CGRP, respectively, all P < .05). Compared to the low to moderate myopia group, the high myopia group (corrected SE greater than −6.00 diopters) had a significantly greater decrease in CNFD, significantly higher tear substance P concentrations at 1 week, 1 month, and 6 months, and significantly higher tear CGRP concentrations at 1 and 6 months. CONCLUSIONS: These results provide new insight into the neurobiological responses and their potential implications in corneal nerve damage and recovery after SMILE. High myopia treatment was associated with greater corneal denervation and neuroinflammation. [ J Refract Surg . 2021;37(8):516–523.]

Background/purpose In 2017, Long-Fa Temple, an illegal religious asylum in Taiwan, was forced to shut down. Hundreds of chronic mentally ill patients were incarcerated there but provided with no modern psychiatric treatment. This study investigated the effectiveness of providing psychiatric intervention for patients subsequently transferred from Long-Fa Temple to a medical center. Methods In total, 88 patients (mean age: 57.2 years, 52.3% male) who had been incarcerated at Long-Fa Temple were transferred to a southern medical center. The patients underwent comprehensive biological, psychological, and social treatment for 18 months. The patients were evaluated once a month in terms of their psychotic symptoms, self-care, nutrition status, cognitive function, occupational function, and family function. Results Regarding the patients' length of stay, 18.2% were incarcerated in Long-Fa Temple for less than 10 years, 21.6% for 10–20 years, and 60.2% for more than 20 years. In terms of psychiatric diagnosis, 98.9% of the patients had been diagnosed with a schizophrenia spectrum disorder. During the 18-month treatment period, negative symptoms decreased significantly, while the patients’ self-care ability, nutrition status, cognition, occupational function, and family function all significantly improved over time. Patients who had been incarcerated for less than 10 years demonstrated better improvements in psychotic symptoms, self-care, nutrition status, and cognitive function. Conclusion Contemporary psychiatric intervention is beneficial for chronically untreated mentally ill patients, and the patients who had a shorter duration of illness had a better reserve of recovery. These findings can serve as an important reference for psychiatric intervention in developing countries.

A Sn-ball was integrated with a colloidal quantum dot light-emitting diode package to achieve effective heat and reliability management. The electric, optical intensity, and heat distributions of the package were evaluated under various radiant fluxes; data were collected at the 90th hour of aging. Under 1 W/cm2, the areal temperature decreased from 38.5 °C (without Sn-ball) to 32.3 °C (with Sn-ball), which helped extend the lifetime of the colloidal quantum dots in the package. Specifically, the introduction of the metal ball structure engendered a two- to three-fold increase in lifetime. The study findings could contribute toward integrating quantum dots into photonic devices.

Background The coronavirus disease 2019 (COVID‐19) pandemic forced healthcare systems to rethink healthcare delivery, and forced primary care pharmacists in our healthcare system to switch all visits that were previously face to face (FTF) to telehealth. Methods We conducted a retrospective observational cohort study to examine the association between medication related problems (MRPs) resolved in telehealth vs FTF primary care clinical pharmacist visits. The telehealth visits took place in the context of the COVID‐19 pandemic, which forced health care systems to rethink care delivery. Data was collected for patient visits for 2 weeks in January before the pandemic and 2 weeks in June during the pandemic. Results There was significantly more average MRPs resolved per patient encounter in FTF visits compared with telehealth visits, particularly in patient encounters that were previously seen by the pharmacist, who were under 65 years old, identified as Black/African American, had chronic kidney disease but not on dialysis, diabetes with end organ damage, and had uncontrolled blood pressure and uncontrolled A1c. Conclusion These results provide a start to establish criteria for which patients should be seen by a clinical pharmacist in person vs over the phone.

Public health crises like the ongoing COVID-19 pandemic appear to be the perfect breeding ground for misinformation. As influential information sources, mainstream news media have a unique opportunity to use their platform to debunk and educate the public about misinformation. Despite evidence lending support to the potential for mainstream news media to play a larger role in combating misinformation in society, empirical explorations of how they have contributed to the management of misinformation remain scant. This study aims to address these major gaps in research by investigating how mainstream news dailies gatekeep and correct COVID-19 related misinformation in Singapore. The content of 164 news articles published by the mainstream news dailies in Singapore from January 1 to April 30, 2020 on COVID-19 misinformation was analyzed qualitatively and quantitatively. Results show that the two main types of misinformation, fabricated and reconfigured misinformation, were covered almost equally by mainstream news media. Misinformation related to science and health were most frequently reported, followed by scams, and government policy. Statistically significant differences were found between how mainstream news media corrected the various types and topics of misinformation. Significant differences were also found within the various types, topics, and corrections of misinformation across the early stages of the pandemic. Taken together, these findings shed light on the critical role of mainstream news media as public education tools to correct misinformation during public health crises. From a theoretical perspective, these findings contribute to the understanding of media misinformation gatekeeping, and misinformation correction. From a practical perspective, it highlights the capacity and potential roles of the press in supporting government efforts to combat misinformation. Ministry of Health (MOH) National Medical Research Council (NMRC) This work was supported by Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF-005).

PurposeThis study aims to investigate the relationship between Internet celebrity characteristics and the follower's impulse purchase behavior in YouTuber. Attachment and parasocial interaction are mediating variables concerning the impact of Internet celebrity characteristics on followers' impulse purchase behavior.Design/methodology/approachThis study conducted an online survey of YouTube users in Taiwan and utilized quota sampling with 500 samples to examine the influence of two types of Internet celebrities on impulse purchase behavior.FindingsAs to the empirical results, the main path indicated that the self-disclosure Internet celebrity positively affected the attachment, which mainly positively affected the impulse purchase behavior. The second path showed that the expertise-knowledge Internet celebrity positively affected the attachment, which positively affected the impulse purchase behavior.Practical implicationsYouTube marketers should proceed prudently with the market segmentation and choose the appropriate type of Internet celebrities who are suitable for the product image to differentiate marketing. Empirical results can aid marketers in selecting a product-endorser, and enhance consumers' purchasing effect on product advertisements in interactive marketing.Originality/valueThe novelty of this study is to explore the mediation effect of the impact of Internet celebrity characteristics on followers' impulse purchase behavior in interactive marketing. The explaining mechanism of attachment and parasocial interaction is promised to be highlighted as the contribution of this study to the extant literature. This study constructs a theoretical mechanism between attachment theory and parasocial interaction theory and then can be used as a theoretical lens for designing successful social media strategies and explaining social media brand relationships.

Intersected nonpolar ZnO nanosail arrays were fabricated epitaxially on Au‐coated LiGaO2 (010) substrate by chemical vapor deposition. In spite of five growth directions, the novel two‐dimensional (2D) nanostructure was confirmed to be single‐crystalline by X‐ray diffraction and transmission electron microscopy. The anisotropy of growth and surface energy in three directions as well as the equivalency of crystallography should be responsible for the formation of intersected 2D nanosail arrays. Compared with those of polar nanoprisms and nonpolar film samples, the nanosail arrays exhibit superior photoelectrochemical performances of photocurrent density (620 µA cm–2 at 0.2 V vs. SCE) and photoconversion efficiency. The enhanced photoelectrochemical responses were attributed to the unique nanostructure with large surface area and high surface‐to‐volume ratio as well as nonpolar characteristic. This work demonstrates a simple, low‐cost and pattern‐free pathway to prepare aligned 2D nanosail arrays for technological applications.

Intermetallic compound(s) (IMC) that nucleates at the interface between solder and Cu trace during a soldering reaction, is one of the most crucial factors for microelectronic packaging reliability. This study was conducted to modify the IMC microstructure and to reinforce the mechanical strength of Sn–Ag–Cu/Cu microelectronic joints through various surface finish coatings, including organic solderability preservative (OSP), immersion Ag (ImAg), immersion Sn (ImSn), Au/Pd (electroless palladium/immersion gold, EPIG), and Au/Pd/Au (IGEPIG) layer(s). We confirmed that the type of surface finish dominated the IMC growth morphology and mechanical characteristics of the Sn–Ag–Cu/Cu solder joints, even though these surface finishes were eliminated in a few seconds of the soldering process. A dense Cu6Sn5 layer with a scallop-like appearance was obtained for the traditional OSP case, while a prismatic, loose Cu6Sn5 microstructure was produced for the alternative cases (metal films). This loose Cu6Sn5 microstructure offered numerous molten solder channels for the in-diffusion of Sn to Cu, retarding undesired Cu3Sn growth at the Cu6Sn5/Cu interface; consequently, a brittle-to-ductile transition in the joint fracture mode with a high shear strength and fracture energy was obtained in the high-speed ball shear (HSBS) test. A significant mechanical reinforcement of the Sn–Ag–Cu/Cu microelectronic joints can be achieved with the replacement of the traditional OSP coating by the newly developed IGEPIG trilayer surface finish.

Cognitive deficits, which are core manifestations in schizophrenia and exhibit a limited response to antipsychotic treatment, contribute to poor treatment outcomes and functional disability. Evidence on the effect of aerobic walking (AW) and exercise intensity on cognitive function in patients with schizophrenia is lacking. In total, 79 patients with schizophrenia were recruited for a 12-week randomized control trial and allocated to the treatment-as-usual (TAU, n = 38) and treatment-as-usual plus AW (TAW, n = 39) groups. The TAW participants joined a supervised 12-week AW program consisting of 30-min sessions five times per week while wearing a Fitbit Charge 2 device. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. After randomization, 67 (34 TAU and 33 TAW) participants joined the 12-week trial and were included in the intention-to-treat analysis. Multivariate general linear model repeated measures analysis revealed no significant time × group interaction effect on cognitive function changes between the TAU and TAW groups and a marginally significant group effect on verbal fluency (p = 0.09). The interaction effect of time and treatment group on verbal fluency (p = 0.05) was marginally significant between the high and low AW intensity groups, whereas a significant group effect on attention and processing speed (p = 0.04) was observed. Supervised 12-week AW of moderate intensity may have potential cognitive benefits for patients with schizophrenia.

Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorde...

Objectives Chronic inflammation and neuroprogression underlie bipolar disorder (BP) and associated cognitive deficits. Memantine (MM) exerts neuroprotective effects by reducing neuroinflammation. Therefore, we investigated whether add-on low-dose MM (5 mg/day) in BP-II patients may improve cognition and inflammation. Methods We combined two 12-week randomized, double-blind, placebo-controlled studies (NCT 01188148 and NCT 03039842) for analysis. Each participant was allocated to the MM or placebo group. Symptom severity, neuropsychological tests, and the cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were evaluated at baseline and endpoint. A subgroup analysis of middle- to old-aged BP-II patients was also performed. Results We recruited 155 BP-II patients (23 of which were middle- to old-aged) for the MM group and 170 patients (20 of which were middle- to old-aged) for the placebo group. Add-on MM did not result in significant improvements in cognitive functions in all BP-II patients, but a group difference in TNF-α levels was found in the MM group (P=0.04). Specifically, in middle- to old-aged BP-II patients, there was a significant time and group interaction effect on omission T-scores, hit reaction time T-scores, and hit reaction time standard error T-scores on continuous performance tests (CPTs) in the MM group (P=0.007, 0.02, and 0.01, respectively), and a decrease in plasma TNF-α levels (P=0.04). Limitations The sample size of middle- to old-aged BP-II patients were limited. Conclusion Add-on MM may attenuate inflammation in BP-II and improve cognition in middle- to old-aged BP-II patients.

The manufacture of ambient roll-to-roll (R2R) slot-die-coated organic photovoltaic (OPV) is the basis toward commercialization of OPV. The low-cost large-area encapsulation technique of stability improvement of flexible OPV module is under-investigated. The related reports on flexible encapsulation up-scaled from cell were limited. The present study develops an effective and easy encapsulation method and architecture design based on the inverted structure of ambient R2R slot-die-coated PET/ITO/ZnO/active layer/hole transport layer (HTL)/Ag. All module areas are greater than 48 cm2. The P3HT:PCBM and PV2000:PC71BM adopted as active layers have the performance conversion efficiencies of modules of 1–2.2% and 4.2%, respectively. The thermally-deposited MoO3 and slot-die-coated PEDOT:PSS HTLs are used to compare the effect of HTL on T80 lifetime of the large-area flexible R2R module under the accelerated test. The accelerated stability tests regarding to different encapsulation architectures, including damp-heat and light soaking stresses, were conducted. The intrinsic and extrinsic degradation effects are analyzed. We develop the simple encapsulation design effectively suppressing the lateral ingress of oxygen and moisture. The T80 lifetime of P3HT:PCBM-based module can be improved to be 1500 h under the damp-heat test (65 °C/65% RH). The T80 lifetime of PV2000:PC71BM-based module can last for 7000 h under the dark and ambient environment (30 °C/50 ± 20% RH).

Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. Methods A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, “pure” MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. Results Executive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. Conclusions We noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR syndrome. However, the conclusions were based on the enrollment procedure of participants prioritizes the MCR syndrome. Because of the overlap of MCR and MCI, future studies should use different enrollment strategies to further clarify the status of these two populations.

Globalization and communication on the internet poses challenges to sociolinguistics. China is one of the engines of economic in the world. Since the Internet service started in 1994, it has been developing rapidly. The rapid development of Internet communication in China has created huge impact on the Chinese language and society. According to Yates (1996), a new medium of communication such as the Internet not only draws upon existing linguistic practices, but also generates new forms of Chinese Internet lexicon. The rapid diffusion of the Internet has prompted developments in the variety and creativity of language use. Internet users often create new words or appropriate the meanings of existing words. The resultant “Internet language” has unique lexical and discourse features. Li (2002) and Ma (2002) confirmed that Internet lexicon has brought the tremendous impact and spread to everyday usage in Chinese society. In 2006 National Language Resources Monitoring and Research Graphic Media Center has released the first time an annual report of Inventory of Chinese Language (汉语盘点 Hanyu pandian). Since 2011 ten most popular Internet hot words have been released annually by National Language Resources Monitoring and Research Graphic Media Center. This research is aimed to discusses the emergence and use of most popular Chinese Internet vocabularies in the recent 10 years. Based on the data from National Language Resources Monitoring and Research Graphic Media Center, the most popular Chinese Internet words and phrases (2011-2019) are analyzed and summarized into twelve categories. The implication and findings of the symbolic meaning embedded in the Chinese internet lexicon are analyzed. This study sets out to examine the transformation of internet lexicon in China and to argue the equivalent relation between symbols, language and popular culture.

Agribusiness organizations have gained an understanding of the need to promote environmentally friendly actions for the present and the future. Green accounting (GA) or environmental accounting is a new branch of accounting that attempts to factor costs related to the environment into the financial results of various operations. The concept of intellectual capital (IC) describes all the resources or capital that determines an organization’s value and competitiveness. The implementation of GA principles in an agribusiness organization is a cross-disciplinary work that entails sustainability, accounting, and other fields of research. Thus, competent farmers (human capital), good relationships with stakeholders (relational capital), structural changes (organizational capital), and innovativeness (innovation capital) all of which are concepts of IC are needed for the implementation of environmental sustainability policies and procedures within an organization. This conceptual paper explores key success factors for the GA from the IC perspective. We proposed that, for different reasons and logic, the human, customer, organizational, innovation, and process capitals all play roles as key success factors for good implementation of GA in agribusiness.

In this systematic review and meta‐analysis of 86 studies and 526,641 individuals without viral hepatitis and hepatic steatosis, the ALT upper threshold was 39 in overweight patients versus 28 in normal‐weight individuals, and 36 in diabetics versus 33 in nondiabetics. These findings were validated in a multicenter cohort of 6,058 patients. Diabetic and overweight patients with ALT values within these thresholds can potentially avoid extensive and possibly harmful invasive investigations after excluding viral hepatitis and nonalcoholic fatty liver disease. However, close monitoring and management of metabolic factors are required., The current alanine aminotransferase (ALT) upper limit of normal was defined using selected healthy Caucasian blood donors. Given the global rise in obesity and different body habitus in Asians, we aimed to perform a systematic review and meta‐analysis combined with bootstrap modeling and individual patient data validation to estimate the ALT upper threshold for Asians, including the overweight and diabetics. We included studies from PubMed, Embase, and Cochrane database searches that identified individuals without known liver diseases (i.e., viral hepatitis, alcohol, and ultrasound‐detected nonalcoholic fatty liver disease). The mean ALT (U/L) was estimated using a random‐effects mixed model and upper threshold (95th‐percentile value, U/L) via a bootstrap model with 10,000 resamples. We screened 4,995 studies and identified 86 studies that reported ALT values for 526,641 individuals without excessive alcohol intake or known liver diseases, yielding a mean ALT of 19 and ALT upper threshold of 32. The ALT upper threshold was 37 in males versus 31 in females, 39 in overweight versus 28 in normal‐weight individuals, and 36 for diabetics versus 33 for nondiabetics. We validated our study level data with individual patient level data in 6,058 individuals from five study centers in Japan. Consistent with our study‐level data, we found that the ALT upper threshold in our individual patient data analysis was indeed higher in overweight versus normal‐weight individuals (39 vs. 32) and in diabetics versus nondiabetics (42 vs. 33). Conclusion: We provide validated reference ranges for ALT upper threshold derived from Asians without known liver disease, including individuals with ultrasound‐detected nonalcoholic fatty liver disease who are normal weight, overweight, nondiabetic, and diabetic, to inform practice.

OBJECTIVE Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored. METHODS This study included patients in a single-center CKD care program who initiated long-term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression. RESULTS Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28-1.81, p

Purpose This study aims to analyze the link between earnings pressure and R&D cut as well as the moderating effects of family control and debt. Design/methodology/approach In total, 6,130 firm-year observations of Taiwanese-listed firms were used to test the hypotheses by using a panel data regression with fixed effects estimation. Findings The study reveals that earnings pressure is positively related to R&D cut, and this relationship can be softened when having the presence of family control and debt. Research limitations/implications This study is conducted based on some conditions: data collection comes from a single source, earnings pressure mainly comes from analysts, R&D intensity is significant among industries, debt is a given condition to managers. Future studies, thus, are suggested to use other approaches to have further information and extend the knowledge without these conditions. Practical implications Under the pressure of meeting analyst forecast, managers have more opportunities to flourish their priority on improving temporary profits rather than implementing R&D investments with costly budget but unpredictable outcomes. In addition to responding to the positive effect of earnings pressure on trimming long-term corporate investments, this study also found some corporate governance mechanisms to soften the managerial short-termism behavior. Originality/value The findings partially contribute to broadening the existing knowledge base on the impact of earnings pressure on corporate activities and how some mechanisms serve as moderators.

Pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy are the two most common causes of corneal edema after cataract surgery. We report a 61-year-old alcoholic male with bilateral corneal edema that improved after his alcohol abstinence. He had uneventful bilateral cataract surgery 3 years ago and blurred vision in both eyes developed for weeks. As he had no history of endothelial dystrophy, the treatment for viral endotheliitis was used initially yet in vain. We asked him to stop alcohol and adjusted his psychiatric drugs, but he lied about stopping drinking. The corneal edema progressed, and finally, he underwent penetrating keratoplasty in his left eye 1 year later. During hospitalization for surgery, alcohol withdrawal syndrome was noted because he could not drink alcohol in our hospital. After he quit drinking for months, corneal edema in the right eye disappeared. Our case highlights that alcoholism can result in corneal edema, and stopping drinking is necessary in these patients.

Objective: Parkinson disease (PD) is a debilitating neurodegenerative disease. Caring for an individual with PD can have a variety of negative physical and psychological effects on caregivers which may challenge their ability to continue in their caretaking role. The aim of this study was to assess the prevalence and associated factors of depressive disorders in caregivers of individuals with PD using standardized instruments. Methods: This study used a cross-sectional design with consecutive sampling. Study participants were recruited from the neurological ward or neurological outpatient clinic of a medical center from August 2018 to July 2019. Caregivers of persons with PD were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. Results: Of the 162 caregivers that completed the study, 67.3% (n = 109) were females. The most common psychiatric diagnosis was depressive disorder (11.1%), followed by insomnia disorder (7.4%) and anxiety disorder not otherwise specified (4.3%); 28% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, it was found that duration of caregiving (odds ratio [OR] = 1.28; 95% CI, 1.05-1.58), severity of anxiety (OR = 1.86; 95% CI, 1.36-2.53), and severity of fatigue (OR = 1.08; 95% CI, 1.01-1.16) were 3 significant associated factors for the development of depression. Conclusion: Depression was the most prevalent psychiatric diagnosis in caregivers of people with PD. Early diagnosis of these caregivers is crucial to the offering of suitable support and treatment and might improve caregivers’ quality of life.

Background Generic antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders. Methods In a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes. Results A total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20–2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs. Conclusions Compared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder.

Tardive tremor is an infrequently form of tardive syndrome that is developed from prolonged treatment with dopamine receptor blocking agents. This condition presents as a prominent tremor that may cause significant distress but currently lacks effective treatment. Electroconvulsive therapy (ECT) has been applied to treat tardive syndrome. In this study, we report a 74-year-old female patient with major depressive disorder, whose tardive tremor and depressive symptoms showed remarkable improvement after receiving 10 sessions of ECT treatment.

Femtosecond lasers at fixed wavelengths above 1,000 nm are powerful, stable and inexpensive, making them promising sources for two-photon microscopy. Biosensors optimized for these wavelengths are needed for both next-generation microscopes and affordable turn-key systems. Here we report jYCaMP1, a yellow variant of the calcium indicator jGCaMP7 that outperforms its parent in mice and flies at excitation wavelengths above 1,000 nm and enables improved two-color calcium imaging with red fluorescent protein-based indicators. jYCaMP1, a yellow variant of the calcium indicator jGCaMP7, enables fast multicolor two-photon imaging at excitation wavelengths above 1,000 nm for use with popular ytterbium-doped fiber and modelocked semiconductor lasers.

Objective Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients. Methods Data on patients with HCC at BCLC stage C from August 2012 to September 2017 were collected. Patients who were given sorafenib alone were classified as the monotherapy group and those taking sorafenib and TACE were classed as the combined therapy group. Results A total of 118 patients were enrolled. There were 65 and 53 patients in the monotherapy and the combined therapy group, respectively. The groups' general characteristics were similar. Compared with the monotherapy group the combined therapy group experienced prolonged time-to-progression (TTP) (mean 6.42 mo vs 3.63 mo, P = 0.003) and overall survival (OS) (mean 11.21 mo vs 5.98 mo, P = 0.001). A subgroup analysis found that patients with macroscopic vascular invasion (MVI) also had prolonged TTP and OS in the combined therapy group than the monotherapy group (mean TTP, 7.93 mo vs 3.43 mo, P = 0.007; mean OS, 13.41 mo vs 5.50 mo, P = 0.001), however, these significant differences did not exist for those with extrahepatic spread (EHS). Conclusion Combined sorafenib and TACE therapy has significant better outcomes than sorafenib alone in patients with stage C HCC, particularly those with MVI.

Objectives In this study, we determined the incidence and pattern of screw loosening in patients who received dental implants. Materials and Methods Patients who received implants between January 2008 and October 2013 and completed their prosthetic rehabilitation were evaluated for the incidence, frequency, and onset of screw loosening using dental charts and radiographs. The association between each factor and screw loosening was analyzed using the chi-square test and a multivariate analysis with binary logistic regression models (P

Background The aim of this study is to determine whether adding combination of agents with anti-inflammatory and neurotrophic effects is more efficacious than mood stabilizer alone in improving clinical symptoms, plasma brain-derived neurotrophic factor (BDNF), cytokine levels, and metabolic profiles in patients with bipolar spectrum disorder. Methods In a randomized, double-blind, controlled 12-week clinical trial, patients with moderate mood symptoms (HDRS ≥ 18 or YMRS ≥ 14) were recruited. The patients were randomly assigned to a group while still undergoing regular valproate (VPA) treatments: VPA + dextromethorphan (DM) (30 mg/day) + memantine (MM) (5 mg/day) (DM30 + MM5) (n = 66), VPA + DM (30 mg/day) (DM30) (n = 69), VPA + MM (5 mg/day) (MM5) (n = 66), or VPA + Placebo (Placebo) (n = 69). Symptom severity, immunological parameters [plasma tumor necrosis factor (TNF)-α and C-reactive protein (CRP)] and plasma brain-derived neurotrophic factor (BDNF) were regularly examined. Metabolic profiles [cholesterol, triglycerides, glycosylated hemoglobin (HbA1C), fasting serum glucose, body mass index (BMI)] were measured at baseline and at 2, 8, and 12 weeks. Results Depression scores were significantly (P = 0.03) decreases and BDNF levels significantly (P = 0.04) increased in the DM30 + MM5 group than in the Placebo group. However, neither depressive scores nor BDNF levels were significantly different between the DM30, MM5, and Placebo groups. Changes in certain plasma cytokine and BDNF levels were significantly correlated with metabolic parameters. Conclusion We concluded that add-on DM30 + MM5 was significantly more effective than placebo for clinical symptoms and plasma BDNF levels. Additional studies with larger samples and mechanistic studies are necessary to confirm our findings. Trial registration NCT03039842 (https://register.clinicaltrials.gov/). Trial date was from 1 Jan 2013 to 31 December 2016 in National Cheng Kung University Hospital. Registered 28 February 1 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03039842?term=NCT03039842&rank=1.

OBJECTIVES The relationship between metabolic syndrome (MetS) components and leukocyte telomere length (LTL) attrition in major depressive disorder (MDD) remains unclear. METHODS We recruited 70 MDD patients (mean age: 44.6 years, 60.0% female) and 51 age- and sex-matched controls (mean age: 41.2 years, 68.6% female) to examine the associations of MetS components and LTL. Five MetS components-waist circumference, systolic/diastolic blood pressure, serum levels of fasting glucose, high-density lipoprotein cholesterol (HDL-C), and triglycerides-were assessed. LTL was measured through quantitative polymerase chain reaction. RESULTS MDD had higher prevalence of MetS (34.3% vs. 17.6%, p = .042), low HDL-C (25.7% vs. 7.8%, p = .009) and shorter LTL (-.038 ± .169 vs. .033 ± .213, p = .042). Regression analysis revealed that MDD (p =.046) and age (p =.003) associated with LTL, while a significant interaction effect of group (MDD vs. controls) x HDL-C (p = .037) was observed. Post-hoc analysis showed MDD with low HDL-C had greater LTL attrition than controls without low HDL-C (p = .020). In MDD, HDL-C dysregulation negatively correlated with LTL (p =.010); but no significance after Bonferroni correction. CONCLUSIONS HDL-C may be involved in accelerated aging process regarding metabolic disturbance in MDD only. The relationship merits prospective investigations with larger sample size for clarification.

Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (&gt, 0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.