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Osteoarthritis (OA) is a multifactorial joint disease and a common disabling condition in the elderly population. The associated pain and pathohistological changes in cartilage are common features of OA in both humans and animal models. Shea nut oil extract (SheaFlex75) contains a high triterpenoid concentration and has demonstrated anti-inflammatory and antiarthritic effects in both human and animal studies. In this study, we aim to investigate the potential of SheaFlex75 to prevent articular cartilage deterioration in a rat model of chronic OA progression. By employing anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx)-induced OA, we found attenuation of both early and chronic onset OA pain and cartilage degeneration in ACLT+MMx rats receiving SheaFlex75 dietary supplementation. Under long-term oral administration, the rats with induced OA presented sustained protection of both pain and OA cartilage integrity compared to the OA-control rats. Moreover, rats subjected to long-term SheaFlex75 ingestion showed normal biochemical profiles (AST, BUN and total cholesterol) and presented relatively lower triglycerides (TGs) and body weights than the OA-control rats, which suggested the safety of prolonged use of this oil extract. Based on the present evidence, preventive management is advised to delay/prevent onset and progression in OA patients. Therefore, we suggest that SheaFlex75 may be an effective management strategy for symptom relief and cartilage protection in patients with both acute and chronic OA. [ABSTRACT FROM AUTHOR]

Background: The impact of leukoaraiosis on the risk of symptomatic intracerebral hemorrhage (SICH) after stroke thrombolysis is conflicting, and the data on Asian populations are lacking. Therefore, in this study, we assessed the association between leukoaraiosis and SICH, and the association between leukoaraiosis and the 90-day functional outcome in the Asian population. Methods: Data were collected from a two-center prospective registry of acute ischemic stroke patients given intravenous tissue plasminogen activator between 2006 and 2014. A total of 614 pretreatment brain CT and 455 posttreatment MRI were retrospectively assessed using two different rating scales for the presence of leukoaraiosis. Outcome measures were the occurrence of SICH with three definitions and any hemorrhage after thrombolysis and functional outcome at 3 months. Results: Of the 614 patients assessed, 30.3% showed severe leukoaraiosis on the baseline brain CT. The SICH rate was 4.6% - 7.2% based on different definitions, and overall, 24.9% of patients showed any post-tPA hemorrhage. No association was observed between the severity of leukoaraiosis and SICH, regardless of having used different leukoaraiosis rating scales or as assessment using different imaging modalities. However, severe leukoaraiosis was independently associated with poor functional outcome at 3 months (OR 1.96, 95% C1 1.24–3.11, P = 0.004) after adjustment for confounders. Conclusions: Our results showed no association between leukoaraiosis and the risk of SICH. Although the presence of severe leukoaraiosis predicted a poor functional outcome after stroke, IV thrombolysis might not be withheld in acute ischemic stroke patients solely based on the presence of severe leukoaraiosis on pre-thrombolytic CT scans. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to support the potential protective role of anterior cruciate ligament (ACL) reconstruction against the development of osteoarthritis (OA). Methods: In this retrospective cohort study, the long-term results of ACL reconstruction in Taiwan were evaluated based on data from the National Health Insurance Research Database (NHIRD). In total, 8,769 eligible cases were included from 11,921 ACL-injured patients. The cumulative incidence rates of OA and total knee replacement (TKR) were analyzed using the Kaplan-Meier estimator. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of OA. Results: There was a lower cumulative incidence of OA among ACL-reconstructed patients (271, 33.1%) than among non-reconstructed patients (1,874, 40.3%; p < 0.001). Patients who underwent ACL reconstruction had a lower cumulative incidence of TKR during the follow-up period (0.6%) than the non-reconstructed patients (4.6%, p < 0.001). After adjusting for covariates, ACL-injured patients who underwent reconstruction within one month after ACL injury showed a significantly lower risk of OA than those who never underwent reconstruction (adjusted HR = 0.83, 95% CI = 0.69–0.99). Conclusions: These results indicate that ACL reconstruction might not provide complete protection from OA development after traumatic knee injury but does yield a lower cumulative incidence of OA development and TKR. Moreover, based on the present study, ACL-injured patients should undergo reconstruction as early as possible (within one month) to lower the risk of OA. [ABSTRACT FROM AUTHOR]

Background and Objectives: Complete surgical resection is recommended for early stage lung cancer, and adjuvant chemotherapy is given for stage IB to IIIA disease. No studies have examined the best timing to administer chemotherapy after surgery in lung cancer. This study was to investigate the optimal timing of adjuvant chemotherapy after surgical resection. Methods: Data collected from the Taiwan National Health Insurance Research Database between January, 2004 and December, 2010 were retrospectively analyzed. Patients with stage IB to IIIA lung cancer underwent complete surgical resection and adjuvant chemotherapy were included. A total of 1522 patients were included. The patients were divided into 4 groups according to the interval between surgery and chemotherapy: group 1, < 30 days; group 2, 30–45 days; group 3, 46–60 days; group 4 > 60 days. Univariate and multivariate regression analyses were used to identify prognostic factors for overall survival. Results: The numbers of patients in groups 1, 2, 3, and 4 were 153, 161, 290, and 818, respectively. The 5-year survival rate was 41% in group 1, 48% in group 2, 50% in group 3, and 35% in group 4 (p<0.001). The median survival time was 44.50 months in group 1, 59.53 months in group 2, 67.33 months in group 3 and 36.33 months in group 4 (p<0.001) Survival rate is the poorest when chemotherapy is delayed beyond 60 days after surgical resection Multivariate analysis also indicated the interval between surgery and first course of chemotherapy more than 60 days after surgery was an independent risk factor for survival. Conclusions: Timing of chemotherapy after surgery is associated with poorer survival in lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria. Methods: We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist’s structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists’ clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy. Results: Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use. Conclusion: The diagnostic criteria of smartphone addiction demonstrated the core symptoms “impaired control” paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment. [ABSTRACT FROM AUTHOR]

Background: Shea nut oil triterpene concentrate is considered to have anti-inflammatory and antioxidant properties. Traditionally, it has been used to treat arthritic conditions in humans. This study aimed to investigate the effect of attenuating osteoarthritis (OA)-induced pain and joint destruction in rats by administering shea nut oil triterpene concentrate (SheaFlex75, which is more than 50% triterpenes). Methods: An anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was used to induce OA in male Wistar rats. Different doses of SheaFlex75 (111.6 mg/kg, 223.2 mg/kg, and 446.4 mg/kg) were then intragastrically administered daily for 12 weeks after surgery. Body weight and the width of the knee joint were measured weekly. Additionally, incapacitance tests were performed at weeks 2, 4, 6, 8, 10 and 12 to measure the weight bearing of the hind limbs, and the morphology and histopathology of the medial femoral condyles were examined and were evaluated using the Osteoarthritis Research Society International (OARSI) scoring system. Results: This study showed that SheaFlex75 reduced the swelling of the knee joint with OA and rectified its weight bearing after ACLT plus MMx surgery in rats. Treatment with SheaFlex75 also decreased ACLT plus MMx surgery-induced knee joint matrix loss and cartilage degeneration. Conclusion: SheaFlex75 relieves the symptoms of OA and protects cartilage from degeneration. SheaFlex75 thus has the potential to be an ideal nutraceutical supplement for joint protection, particularly for injured knee joints. [ABSTRACT FROM AUTHOR]

This study was to evaluate the association between metabolic syndrome (MetS) and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (anti-HCV) screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC) was 10 kPa for chronic hepatitis B (CHB) patients and 12 kPa for chronic hepatitis C (CHC) patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7%) CHB patients coexisted with MetS whereas 40 (25.6%) CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively). In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR): 0.42; 95% confidence interval (CI): 0.18–0.99; p = 0.047). Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02–1.19; p = 0.012). In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS. [ABSTRACT FROM AUTHOR]

The most common cystic fibrosis (CF) causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del), results in functional expression defect of the CF transmembrane conductance regulator (CFTR) at the apical plasma membrane (PM) of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER). Deletion of phenylalanine 670 (ΔF670) in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter) of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic) analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer is the predominant type of lung cancer, resulting in high mortality worldwide. Digoxin, a cardiac glycoside, has recently been suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an important role in cancer progression and is therefore a potential target for cancer therapy. Here, we investigated whether digoxin could suppress lung cancer progression through the inhibition of Src activity. The effects of digoxin on lung cancer cell functions were investigated using colony formation, migration and invasion assays. Western blotting and qPCR assays were used to analyze the mRNA and protein expression levels of Src and its downstream proteins, and a cell viability assay was used to measure cellular cytotoxicity effects. The results of the cell function assays revealed that digoxin inhibited the proliferation, invasion, migration, and colony formation of A549 lung cancer cells. Similar effects of digoxin were also observed in other lung cancer cell lines. Furthermore, we found that digoxin significantly suppressed Src activity and its protein expression in a dose- and time-dependent manner as well as reduced EGFR and STAT3 activity. Our data suggest that digoxin is a potential anticancer agent that may suppress lung cancer progression through inhibiting Src and the activity of related proteins. [ABSTRACT FROM AUTHOR]

To elucidate the results of post-screening care stratagems for anti-hepatitis C virus (HCV)-positive subjects in the community. Part I methods: The intervention program: A total of 151,790 subjects underwent a large-scale healthcare screening. Subjects aged less than 65 years, with anti-HCV-positive and alanine aminotransferase (ALT) level more than 80 IU/L were followed-up to answer a structured questionnaire. Those responders who met the reimbursement criteria of Taiwan’s National Health Insurance for anti-HCV treatment were referred for treatment. Part II: The accessible medical care program: In Yujing township, 271 HCV residents who have been screened before were invited to a bi-weekly hepatitis clinic in Yujing health center. Part-I results: A total of 907 anti-HCV-positive subjects responded and 197(21.7%) were advised the treatment, but only 83(9.2%) did. Finally, 47 patients achieved a sustained virological response (SVR). After this intervention program, 96(10.6%) additional patients were encouraged to be referred, 33(3.6%) received treatment and 20 obtained a SVR. Part II: A total of 140(51.7%) subjects responded and 112 were anti-HCV-positive including 31(27.7%) HCV RNA-negative, 49(43.8%) HCV RNA-positive plus ALT less than 40 IU/L and 32(28.5%) HCV RNA-positive plus ALT more than 40 IU/L. During the follow-up, 14 of 49 patients had ALT more than 40 IU/L. Among 46 eligible HCV patients, 15(32.6%) received treatment and 10 achieved a SVR. Simple notification only made 9.2% of the screened HCV patients treat. Active referral could encourage additional 3.6% to be treated. Additionally, accessible medical care program could result in treatment of 32.6% elderly eligible patients. [ABSTRACT FROM AUTHOR]

Background: Suicide is the leading cause of death among 15–34 year olds in China, but no national data are available on the suicide and suicide attempts rates of college students, a sub-group of youth with 23 million. Several studies have reported the prevalence of suicide attempts among college students, however, no meta-analysis pooling the prevalence of suicide attempts is found. Objective and Methods: This study aims to estimate the pooled prevalence of suicide attempts among college students in China. The relevant studies up to August 2014 were systematically searched via electronic databases (PubMed-Medline, Embase, Chinese Wanfang database, Chinese National Knowledge Infrastructure and Chinese VIP database). We only selected original articles that either reported the prevalence of suicide attempts or sufficient data for calculating the prevalence. Results: A total of 29 eligible studies, with 88,225 college students, were finally included. The maximum and minimum reported prevalences of suicide attempts among college students in China were 0.4% and 10.5%, respectively. The pooled prevalence of suicide attempts was 2.8% (95%CI: 2.3%–3.3%). Subgroup analyses showed that the pooled estimate of prevalence of life time suicide attempts was 2.7% (95%CI: 2.1%–3.3%), and 12-month suicide attempts was 2.9% (95%CI: 2.0%–3.8%). The prevalence for males was 2.4% (95%CI: 1.8%–3.0%), and for females was 2.7% (95%CI: 1.9%–3.7%). The prevalences among college students in grade 1 through 4 were 2.8% (95%CI: 1.7%–3.8%), 1.8% (95%CI: 1.2%–2.3%), 2.0% (95%CI: 0.8%–3.1%), and 2.9% (95%CI: 0.1%–6.7%), respectively. The prevalences among college students from rural and urban areas were 5.1% (95%CI: 2.8%–7.5%) and 3.7% (95%CI: 1.4%–5.9%), respectively. Conclusions: 2.8% prevalence of suicide attempts and more than 600,000 suicide attempters among college students indicate that suicide attempt among college students is an important public health problem in China. More attention should be paid to the current situation. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-10 levels are increased in dengue virus (DENV)-infected patients with severe disorders. A hypothetical intrinsic pathway has been proposed for the IL-10 response during antibody-dependent enhancement (ADE) of DENV infection; however, the mechanisms of IL-10 regulation remain unclear. Principle Finding: We found that DENV infection and/or attachment was sufficient to induce increased expression of IL-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic THP-1 cells and human peripheral blood monocytes. IL-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (CREB), primarily through protein kinase A (PKA)- and phosphoinositide 3-kinase (PI3K)/PKB-regulated pathways, with PKA activation acting upstream of PI3K/PKB. DENV infection also caused glycogen synthase kinase (GSK)-3β inactivation in a PKA/PI3K/PKB-regulated manner, and inhibition of GSK-3β significantly increased DENV-induced IL-10 production following CREB activation. Pharmacological inhibition of spleen tyrosine kinase (Syk) activity significantly decreased DENV-induced IL-10 production, whereas silencing Syk-associated C-type lectin domain family 5 member A caused a partial inhibition. ADE of DENV infection greatly increased IL-10 expression by enhancing Syk-regulated PI3K/PKB/GSK-3β/CREB signaling. We also found that viral load, but not serotype, affected the IL-10 response. Finally, modulation of IL-10 expression could affect DENV replication. Significance: These results demonstrate that, in monocytes, IL-10 production is regulated by ADE through both an extrinsic and an intrinsic pathway, all involving a Syk-regulated PI3K/PKB/GSK-3β/CREB pathway, and both of which impact viral replication. [ABSTRACT FROM AUTHOR]

Dopaminergic PC12 cells can synthesize and release dopamine, providing a good cellular model for investigating dopamine regulation. Optogenetic stimulation of channelrhodopsin-2 provides high spatial and temporal precision for selective stimulation as a powerful neuromodulation tool for neuroscience studies. The aim of this study is to measure dopamine release from dopaminergic PC12 cells under optogenetic stimulation using electrochemical recording of self-assembled monolayers modified microelectrode with amperometric measurement in real time. The activation of PC12 cells under various optogenetic stimulation schemes are characterized by measuring single-cell Ca2+ imaging. After 10 seconds of optogenetic stimulation, the evoked intracellular Ca2+ level and dopamine current of channelrhodopsin-2-transfected PC12 cells were 1.6- and 3.5-fold higher than those of the control cells. The optogenetic stimulation effects on Ca2+ influx and dopamine release were 81% and 63% inhibition by using a Ca2+ channel antagonist Nifedipine. The results indicate that optogenetic stimulation can evoke voltage-gated Ca2+ channel-dependent dopamine exocytosis from PC12 cells in a cell specific, temporally precise and dose-dependent manner. This proposed dopamine recording system can be developed to be a good cell model for dopamine regulation and drug screening in vitro, or dopaminergic cell implantation therapy in vivo using optogenetic stimulation in a precise and convenient way. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis continues to be a major global health problem. We wanted to investigate whether Type 2 diabetes was a risk factor for tuberculosis in an Asian population. Methods: From Taiwan’s National Health Insurance Research Database, we collected data from 31,237 female patients with type 2 diabetes and 92,642 female controls and 32,493 male patients with type 2 diabetes and 96,977 male controls. Cox proportional hazard regression was performed to evaluate independent risk factors for tuberculosis in all patients and to identify risk factors in patients with type 2 diabetes. Results: During the study period, both female (standardized incidence ratio (SIR): 1.40, p<0.01) and male (SIR: 1.48, p<0.01) patients with type 2 diabetes were found to have a significantly higher rate of incident tuberculosis than the control group. Type 2 diabetes (HR:1.31, 1.23–1.39, p<0.001) was significantly associated with tuberculosis after adjusting sex, age, bronchiectasis, asthma and chronic obstructive lung disease. Conclusions: Patients with type 2 diabetes have a higher risk of tuberculosis compared to control subjects after adjusting for confounding factors. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions. Therefore, preventive measures, including addressing the possibility that type 2 diabetes increase the individual’s susceptibility for incident TB, should be taken to further reduce the incidence of tuberculosis. [ABSTRACT FROM AUTHOR]

Fructose-1,6-bisphosphatase, a key enzyme in gluconeogenesis, is subject to metabolic regulation. The human muscle isozyme is significantly more sensitive towards the allosteric inhibitor, AMP, than the liver isoform. Here we report crystal structures and kinetic studies for wild-type human muscle Fru-1,6-Pase, the AMP-bound (1.6 Å), and product-bound complexes of the Q32R mutant, which was firstly introduced by an error in the cloning. Our high-resolution structure reveals for the first time that the higher sensitivity of the muscle isozyme towards AMP originates from an additional water-mediated, H-bonded network established between AMP and the binding pocket. Also present in our structures are a metaphosphate molecule, alternate conformations of Glu97 coordinating Mg2+, and possible metal migration during catalysis. Although the individual subunit is similar to previously reported Fru-1,6-Pase structures, the tetrameric assembly of all these structures deviates from the canonical R- or T-states, representing novel tetrameric assemblies. Intriguingly, the concentration of AMP required for 50% inhibition of the Q32R mutant is increased 19-fold, and the cooperativity of both AMP and Mg2+ is abolished or decreased. These structures demonstrate the Q32R mutation affects the conformations of both N-terminal residues and the dynamic loop 52–72. Also importantly, structural comparison indicates that this mutation in helix α2 is detrimental to the R-to-T conversion as evidenced by the absence of quaternary structural changes upon AMP binding, providing direct evidence for the critical role of helix α2 in the allosteric signal transduction. [ABSTRACT FROM AUTHOR]

The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects, do not cure the disease and are subject to development of resistance. Finding new therapeutic targets and drugs is therefore crucial. We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4+ T lymphocytes (CD4TL). Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells. Here we report the 3D modelling of the extracellular domain of DCIR. Based on this structure, two surface accessible pockets containing the carbohydrate recognition domain and the EPS binding motif, respectively, were targeted for screening of chemicals that will disrupt normal interaction with HIV-1 particle. Preliminary screening using Raji-CD4-DCIR cells allowed identification of two inhibitors that decreased HIV-1 attachment and propagation. The impact of these inhibitors on infection of DCs and CD4TL was evaluated as well. The results of this study thus identify novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL. [ABSTRACT FROM AUTHOR]

Background: Phantom vibration syndrome is a type of hallucination reported among mobile phone users in the general population. Another similar perception, phantom ringing syndrome, has not been previously described in the medical literature. Methods: A prospective longitudinal study of 74 medical interns (46 males, 28 females; mean age, 24.8±1.2 years) was conducted using repeated investigations of the prevalence and associated factors of phantom vibration and ringing. The accompanying symptoms of anxiety and depression were evaluated with the Beck Anxiety and Depression Inventories before the internship began, and again at the third, sixth, and twelfth internship months, and two weeks after the internship ended. Results: The baseline prevalence of phantom vibration was 78.1%, which increased to 95.9% and 93.2% in the third and sixth internship months. The prevalence returned to 80.8% at the twelfth month and decreased to 50.0% 2 weeks after the internship ended. The baseline prevalence of phantom ringing was 27.4%, which increased to 84.9%, 87.7%, and 86.3% in the third, sixth, and twelfth internship months, respectively. This returned to 54.2% two weeks after the internship ended. The anxiety and depression scores also increased during the internship, and returned to baseline two weeks after the internship. There was no significant correlation between phantom vibration/ringing and symptoms of anxiety or depression. The incidence of both phantom vibration and ringing syndromes significantly increased during the internship, and subsequent recovery. Conclusion: This study suggests that phantom vibration and ringing might be entities that are independent of anxiety or depression during evaluation of stress-associated experiences during medical internships. [ABSTRACT FROM AUTHOR]

Background: On-call duty among medical interns is characterized by sleep deprivation and stressful working conditions, both of which alter cardiac autonomic modulation. We hypothesized that sleep stability decreased in medical interns during on-call duty. We used cardiopulmonary-coupling (CPC) analysis to test our hypothesis. Methods: We used electrocardiogram (ECG)-based CPC analysis to quantify physiological parameters of sleep stability in 13 medical interns during on-call and on-call duty-free periods. There were ten 33.5-h on-call duty shifts per month for interns, each followed by 2 on-call duty-free days, over 3 months. Measurements during sleep were collected before, during, and after an on-call shift. Measurements were repeated 3 months later during an on-call duty-free period. Results: The medical interns had significantly reduced stable sleep, and displayed increased latency to the first epoch of stable sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Interns also had significantly increased rapid-eye-movement (REM) sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Conclusion: Medical interns suffer disrupted sleep stability and continuity during on-call night shifts. The ECG-based CPC analysis provides a straightforward means to quantify sleep quality and stability in medical staff performing shift work under stressful conditions. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of neuroendocrine tumors (NETs) is not well illustrated, particularly for Asian countries. Methods: The age-standardized incidence rates and observed survival rates of NETs diagnosed in Taiwan from January 1, 1996 to December 31, 2008 were calculated using data of the Taiwan Cancer Registry (TCR) and compared to those of the Norwegian Registry of Cancer (NRC) and the US Surveillance, Epidemiology, and End Results (SEER) program. Results: During the study period, a total of 2,187 NET cases were diagnosed in Taiwan, with 62% males and a mean age of 57.9 years-old. The age-standardized incidence rate of NETs increased from 0.30 per 100,000 in 1996 to 1.51 per 100,000 in 2008. The most common primary sites were rectum (25.4%), lung and bronchus (20%) and stomach (7.4%). The 5-year observed survival was 50.4% for all NETs (43.4% for men and 61.8% for women, P<0.0001). The best 5-year observed survivals for NETs by sites were rectum (80.9%), appendix (75.7%), and breast (64.8%). Conclusions: Compared to the data of Norway and the US, the age-standardized incidence rate of NETs in Taiwan is lower and the major primary sites are different, whereas the long-term outcome is similar. More studies on the pathogenesis of NETs are warranted to devise preventive strategies and improve treatment outcomes for NETs. [ABSTRACT FROM AUTHOR]

Hepatitis B virus(HBV) infection remains a global problem, despite the effectiveness of the Hepatitis B vaccine in preventing infection. The resolution of Hepatitis B virus infection has been believed to be attributable to virus-specific immunity. In vivo direct evaluation of anti-HBV immunity in the liver is currently not possible. We have developed a new assay system that detects HBV clearance in the liver after the hydrodynamic transfer of a reporter gene and over-length, linear HBV DNA into hepatocytes, followed by bioluminescence imaging of the reporter gene (Fluc). We employed bioluminescence detection of luciferase expression in HBV-infected hepatocytes to measure the Hepatitis B core antigen (HBcAg)-specific immune responses directed against these infected hepatocytes. Only HBcAg-immunized, but not mock-treated, animals decreased the amounts of luciferase expression, HBsAg and viral DNA from the liver at day 28 after hydrodynamic infection with over-length HBV DNA, indicating that control of luciferase expression correlates with viral clearance from infected hepatocytes. [ABSTRACT FROM AUTHOR]

This study explores the force synergy of human digits in both static and dynamic cylindrical grasping conditions. The patterns of digit force distribution, error compensation, and the relationships among digit forces are examined to quantify the synergetic patterns and coordination of multi-finger movements. This study recruited 24 healthy participants to perform cylindrical grasps using a glass simulator under normal grasping and one-finger restricted conditions. Parameters such as the grasping force, patterns of digit force distribution, and the force coefficient of variation are determined. Correlation coefficients and principal component analysis (PCA) are used to estimate the synergy strength under the dynamic grasping condition. Specific distribution patterns of digit forces are identified for various conditions. The compensation of adjacent fingers for the force in the normal direction of an absent finger agrees with the principle of error compensation. For digit forces in anti-gravity directions, the distribution patterns vary significantly by participant. The forces exerted by the thumb are closely related to those exerted by other fingers under all conditions. The index-middle and middle-ring finger pairs demonstrate a significant relationship. The PCA results show that the normal forces of digits are highly coordinated. This study reveals that normal force synergy exists under both static and dynamic cylindrical grasping conditions. [ABSTRACT FROM AUTHOR]

Background:Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs). However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR) to analyze the incidence and distribution of second cancers after the diagnosis of NETs. Methods:NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs) of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of second cancers associated with sex, age, and primary NET sites. Results:A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63%) developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96), especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22). There appeared to be no preference of second cancer type according to the primary sites of NETs. Conclusions:Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted. [ABSTRACT FROM AUTHOR]