Search

Background/Aim: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. Materials and Methods: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. Results: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. Conclusion: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

The WHO identified depressive disorder as one of the three major diseases in the 21st century and studies have shown that patients with depression are more likely than nondepression to have dementia in the future. However, although there are many related studies that point out that depressive disorder is one of the important factor of dementia, however, these findings are not consistent. In addition, there has been no study of evidence-based construction of dementia prediction model of depressive disorder patients for clinical practice. Therefore, this study will use supervised learning techniques to construct a follow-up dementia prediction model for depressive disorder patients to assist depressive disorder patients and their medical staffs to predict his/her possible risk of suffering from dementia, and then develop early intervention and prevention measures.

Resting-state functional connectivity analyses have revealed a significant effect on the inter-regional interactions in brain. The brain age prediction based on resting-state functional magnetic resonance imaging has been proved as biomarkers to characterize the typical brain development and neuropsychiatric disorders. The brain age prediction model based on functional connectivity measurements derived from resting-state functional magnetic resonance imaging has received a lots of interest in recent years due to its great success in age prediction. However, some of the recent studies rely on experienced neuroscientist experts to select appropriate connectivity features in order to build a robust model for prediction while the others just selected the features based on trial-and-error test. Besides, the subjects used in this studies omitted some subjects that can be divided into two groups with less similarity which may confused the prediction model. In this study, we proposed a multi-class age categories discrimination method with the connectivity features selected via K-means clustering with no prior knowledge provided. The experimental results show that with K-means selected features the proposed model better discriminate multi-class age categories.

Anticancer chemotherapeutic drugs mainly trigger apoptosis induction to eliminate malignant cells. However, many cancer cells are chemoresistant because of defective apoptosis induction. Targeting the autophagic pathway is currently regarded as an alternative strategy for cancer drug discovery. Penfluridol, an antipsychotic drug, has been reported to exert oncostatic effects, but the effect of penfluridol on lung cancer remains unknown. Herein, the antitumor activity of penfluridol was determined in vitro in non-small-cell lung cancer (NSCLC) cell lines using MTS, plate clonogenic, and transwell migration assays and in vivo in an orthotopic xenograft model. Flow cytometry, holotomographic microscopy, immunofluorescence, and immunohistochemistry were employed to determine the cell-death phenotype induced by penfluridol in vitro and in vivo. Western blotting and genetic knockdown by small interfering RNA were performed to explore the underlying mechanisms involved in penfluridol-mediated cell death. We uncovered that penfluridol inhibited the viability and motility of NSCLC cells in vitro and in vivo. Penfluridol induced nonapoptotic cell death by blocking autophagic flux and inducing accumulation of autophagosome-related protein, light chain 3 (LC3) B-II, in HCC827 and A549 NSCLC cells, and in an A549 orthotopic xenograft tumor model. Autophagosome accumulation-induced cell viability inhibition by penfluridol was mainly attributed to ATP energy deprivation. Moreover, we observed that patients with lung tumors expressing high LC3B had longer overall and disease-free survival times. Mechanistically, upregulation of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) pathways and activation of p38 mitogen-activated protein kinase (MAPK) were critical for penfluridol-induced autophagosome accumulation. Our findings identify that penfluridol acts as an inducer of ER stress and p38 MAPK activation, which led to UPR-mediated nonapoptotic cell death via autophagosome accumulation-caused energy loss. Penfluridol is clinically used for schizophrenia, and our study results strongly support penfluridol as a repurposed drug for treating NSCLC.

Background: Heart failure is a frequent complication of type 2 diabetes mellitus (T2DM). Plasma cholesterol, particularly the proatherogenic low-density lipoprotein (LDL) cholesterol, impairs heart function by promoting atheroma formation and ventricular dysfunction. Considering the established effect of cholesterol on the cardiovascular system, we hypothesized that plasma LDL cholesterol may influence left ventricular function in individuals with T2DM. Methods: This cross-sectional study was conducted at a tertiary care hospital in Taiwan. Enrollment criteria were patients exceeding 21 years of age with T2DM who received antidiabetic and cholesterol-lowering medications. Candidates were excluded if they had heart failure, acute cardiovascular events, or familial hypercholesterolemia. Participants received blood sampling for plasma lipids after a 12-h fast, followed by transthoracic echocardiography in the cardiology clinic. Results: The study enrolled 118 participants who were divided into two groups according to their plasma LDL cholesterol levels. Demographic characteristics including age (69.7 vs. 66.9 years, P = 0.159), body mass index (26.2 vs. 25.9 kg/m2, P = 0.66), diabetes duration (5.4 vs. 5.1 years, P = 0.48), hemoglobin A1c (7.2 vs. 7.5%, P = 0.225), and systolic blood pressure (129 vs. 130 mm Hg, P = 0.735) were similar between these groups. Moreover, all participants received similar antihypertensive medications. Participants with lower plasma LDL cholesterol levels had better heart function, as measured by the left ventricular ejection fraction (LVEF), than patients with higher LDL cholesterol levels (58.0 vs. 50.5%, P = 0.022). Multivariate regression analysis also showed an inverse correlation between plasma LDL cholesterol and left ventricular function (β coefficient: −0.110, P = 0.024). Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding.

Background/Aim: Matrix metalloproteinase 2 (MMP2) is up-regulated in many cancers. However, the association of MMP2 genotype to nasopharyngeal cancer (NPC) susceptibility in Taiwan remains elusive. Materials and Methods: In this study, the role of MMP2 promoter C-1306T (rs243865) and C-735T (rs2285053) genotypes were investigated among 208 NPC patients and 416 healthy controls, and their role in NPC staging and TNM classifications were examined. Results: There was no differential distribution as for the genotypic or allelic frequencies at MMP2 promoter C-1306T or C-735T between the control and case groups. Noticeably, those with MMP2 C-1306T CT+TT genotypes had a lower metastatic risk than those with CC (p=0.0295). As for staging, T and N classifications, there was no differential distribution in C-1306T genotypes (p>0.05). Also, there was no differential distribution of C-735T genotypes according to different behavioral/clinicopathological characteristics. Conclusion: CT and TT genotypes at MMP2 C-1306T were associated with a significantly decreased risk of NPC metastasis.

Aims and objectives This study applied structural equation modelling to explore the relationships among agitated behaviours, depression, cognitive function and activities of daily living, as well as associations between these factors and urinary incontinence). Background A high prevalence of urinary incontinence is found among institutional older adults with dementia. People with urinary incontinence suffer from increased financial burden and social isolation and experience reduced quality of life. Design Cross-sectional correlational research. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Methods In total, 226 older adults with dementia were recruited through convenience sampling at 15 long-term care facilities in southern Taiwan. The urinary incontinence frequency, agitated behaviours, depression, cognitive function and activities of daily living were evaluated using bladder records, the Cohen-Mansfield Agitation Inventory, the Cornell Scale for Depression in Dementia, the Mini-Mental State Examination and the Barthel Index, respectively. Results Activities of daily living performance was found to be significantly associated with urinary incontinence; however, age, cognitive function, depression and agitated behaviours were not significantly related to urinary incontinence. Age did not have effects on any of the variables tested in this model, whereas activities of daily living performance was significantly associated with cognitive function and depression. Results further showed that cognitive function and depression were mediators between activities of daily living and agitated behaviours. Conclusion Enhanced activities of daily living independency directly reduced urinary incontinence, improved cognitive function, decreased degrees of depression and indirectly reduced agitated behaviours. Relevance to clinical practice The findings could serve as a valuable reference for long-term care facilities in providing effective urinary incontinence care and prevention to older adults with dementia.

Endothelin (ET)-1 is involved in various fibrotic diseases. However, its implication in pleural fibrosis remains unknown. We aimed to study the profibrotic role of ET-1 in tuberculous pleural effusion (TBPE). The pleural effusion ET-1 levels were measured among 68 patients including transudative pleural effusion (TPE, n = 12), parapneumonic pleural effusion (PPE, n = 20), and TBPE (n = 36) groups. Pleural fibrosis, defined as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Additionally, the effect of ET-1 on mesothelial mesenchymal transition (MMT) and extracellular matrix (ECM) producion in human pleural mesothelial cells (PMCs) was assessed. Our findings revealed that effusion ET-1 levels were significantly higher in TBPE than in TPE and PPE, and were markedly higher in TBPE patients with RPT &gt, 10 mm than those with RPT &le, 10 mm. ET-1 levels correlated substantially with residual pleural shadowing and independently predicted RPT &gt, 10 mm in TBPE. In PMCs, ET-1 time-dependently induced MMT with upregulation of &alpha, smooth muscle actin and downregulation of E-cadherin, and stimulated ECM production, furthermore, ET receptor antagonists effectively abrogated these effects. In conclusion, ET-1 induces MMT and ECM synthesis in human PMCs and correlates with pleural fibrosis in TBPE. This study confers a novel insight into the pathogenesis and potential therapies for fibrotic pleural diseases.

Imaging intracellular calcium dynamics to evaluate the cellular activity is crucial for an understanding of the related cell behavior and signal transduction. Identifying spatial-temporal activity patterns in three-dimensional (3D) tumor cell culture can provide novel insights into calcium-associated tumorigenesis and lead to optimizing the tumor-killing strategies. However, the information cannot be obtained without adequate penetration in 3D cell culture. Herein, we develop optical-resolution photoacoustic microscopy (OR-PAM) by tuning the laser wavelength to 627 nm to investigate calcium waves in 3D tumor cell culture using a novel photoacoustic contrast agent, Chlorophosphonazo-III (CPZ). CPZ has a peak optical absorbance at 650 nm. Not like another Bisazo derivative that can also be used for PA calcium imaging, Arsenazo-III, non-toxic and the high survival rate is observed even when cells are treated with 150 μM of CPZ (

This study investigated the effects of tidal volume (TV) on the diagnostic value of pulse pressure variation (PPV) and the inferior vena cava dispensability index (IVC-DI) for volume responsiveness during mechanical ventilation. In patients undergoing elective surgery with mechanical ventilation, different TVs of 6, 9, and 12 mL/kg were given for two min. The left ventricular outflow tract velocity-time integral (VTI) was measured by transthoracic echocardiography. The IVC-DI was measured at sub-xyphoid transabdominal long axis. The PPV was measured via the radial artery and served as baseline. Index measurements were repeated after fluid challenge. VTI increased by more than 15% after fluid challenge, which was considered as volume responsive. Seventy-nine patients were enrolled, 38 of whom were considered positive volume responsive. Baseline data between the response group and the non-response group were similar. Receiver operating characteristic curve confirmed PPV accuracy in diagnosing an increase in volume responsiveness with increased TV. When TV was 12 mL/kg, the PPV area under the curve (AUC) was 0.93 and the threshold value was 15.5%. IVC-DI had the highest diagnostic accuracy at a TV of 9 mL/kg and an AUC of 0.79, with a threshold value of 15.3%. When TV increased to 12 mL/kg, the IVC-DI value decreased. When the TV was 9 and 12 mL/kg, PPV showed improved performance in diagnosing volume responsiveness than did IVC-DI. PPV diagnostic accuracy in mechanically ventilated patients was higher than IVC-DI. PPV accuracy in predicting volume responsiveness was increased by increasing TV.

Background Health-related social media use is common but few health organisations have embraced its potential for engaging stakeholders in service design and quality improvement (QI). Social media may provide new ways to engage more diverse stakeholders and conduct health design and QI activities. Objective To map how social media is used by health services, providers and consumers to contribute to service design or QI activities. Methods The scoping review was undertaken using the Joanna Briggs Institute methodology. An advisory committee of stakeholders provided guidance throughout the review. Inclusion criteria were studies of any health service stakeholders, in any health setting, where social media was used as a tool for communications which influenced or advocated for changes to health service design or delivery. A descriptive numerical summary of the communication models, user populations and QI activities was created from the included studies, and the findings were further synthesised using deductive qualitative content analysis. Results 40 studies were included. User populations included organisations, clinical and non-clinical providers, young people, people with chronic illness/disability and First Nations people. Twitter was the most common platform for design and QI activities. Most activities were conducted using two-way communication models. A typology of social media use is presented, identifying nine major models of use. Conclusion This review identifies the ways in which social media is being used as a tool to engage stakeholders in health service design and QI, with different models of use appropriate for different activities, user populations and stages of the QI cycle.

Background: Identification of malnutrition is especially important in severely injured patients, in whom hypermetabolism and protein catabolism following traumatic injury worsen their nutritional condition. The geriatric nutritional risk index (GNRI), based on serum albumin level and the current body weight/ideal body weight ratio, is useful for identifying patients with malnutrition in many clinical conditions. This study aimed to explore the association between admission GNRI and mortality outcomes of adult patients with polytrauma. Methods: From 1 January 2009 to 31 December 2019, a total of 348 adult patients with polytrauma, registered in the trauma database of a level I trauma center, were recognized and categorized into groups of death (n = 71) or survival (n = 277) and into four nutritional risk groups: a high-risk group (GNRI &lt, 82, n = 87), a moderate-risk group (GNRI 82 to &lt, 92, n = 144), a low-risk group (GNRI 92&ndash, 98, n = 59), and a no-risk group (GNRI &gt, 98, n = 58). Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for mortality. The mortality outcomes of patients at various nutritional risks were compared to those of patients in the no-risk group. Results: The comparison between the death group (n = 71) and the survival group (n = 277) revealed that there was no significant difference in gender predominance, age, pre-existing comorbidities, injury mechanism, systolic blood pressure, and respiratory rate upon arrival at the emergency room. A significantly lower GNRI and Glasgow Coma Scale score but higher injury severity score (ISS) was observed in the death group than in the survival group. Multivariate logistic regression analysis revealed that Glasgow Coma Scale (GCS), odds ratio (OR), 0.88, 95% confidence interval (CI), 0.83&ndash, 0.95, p &lt, 0.001), ISS (OR, 1.07, 95% CI, 1.04&ndash, 1.11, 0.001), and GNRI (OR, 0.94, 95% CI, 0.91&ndash, 0.97, 0.001) were significant independent risk factors for mortality in these patients. The mortality rates for the high-risk, moderate-risk, low-risk, and no-risk groups were 34.5%, 20.1%, 8.5%, and 12.1%, respectively. Unlike patients in the moderate-risk and low-risk groups, patients in the high-risk group had a significantly higher death rate than that of those in the no-risk group. Conclusions: This study revealed that the GNRI may serve as a simple, promising screening tool to identify the high risk of malnutrition for mortality in adult patients with polytrauma.

Internal resorption is a rare condition in permanent teeth, and may result from trauma, caries, or restorative procedures. Internal resorption is usually asymptomatic and is first identified as a round-shaped enlargement of a root-canal space on routine radiographs. Large resorption defects may result in penetration of the tooth into the periodontium through the cementum. The gold-standard treatment consists of debridement and obturation of the pulp space, sealing of the external communication, and restoration of the normal function of the tooth through a nonsurgical or surgical method. In this case presentation, we report on two methods for repair of internal resorption with perforation. The first method consisted of treating the lower right second premolar by conventional endodontic therapy under a microscope, followed by repair with mineral trioxide aggregate. The second method consisted of surgical treatment of the upper right central incisor. The choice of treatment depends on the size of the perforation, its location, and the ability to approach it for repair.

Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains a therapeutic challenge. A strategy for targeting NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. Dihydromyricetin (DHM) is the major flavonoid component derived from Ampelopsis grossedentata, which has a long history of use in medicine. Herein, the molecular mechanisms by which DHM exerts its anticancer effects against NSCLC cells were investigated. Results from MTS, colony formation, Western blot, flow cytometric, and JC-1 mitochondrial membrane potential assays revealed that DHM showed a selective cytotoxic effect against NSCLC cells (A549 and H1975), but not against normal lung (WI-38) fibroblasts, by inducing apoptosis. DHM-induced cell apoptosis occurred through Bcl-w suppression-mediated mitochondrial membrane depolarization, caspase-9/-7/-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in A549 and H1975 cells. Moreover, treatment of A549 and H1975 cells with DHM induced increase of intracellular peroxide and sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2, and the reactive oxygen species scavenger, N-acetylcysteine (NAC), reversed DHM-induced ERK and JNK activation. Furthermore, treatment of cells with specific inhibitors of ERK and JNK or NAC significantly promoted the DHM-induced activation of caspase-9/-7/-3 and PARP cleavage and also sensitized the antitumorigenic effect of DHM on NSCLC cells. These findings define and support a novel function of DHM of inducing mitochondrion-derived apoptosis in human NSCLC cells, and a combination of DHM with ERK and JNK inhibitors should be a good strategy for preventing NSCLC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1426-1438, 2017.

Background/PurposeAeromonas and Vibrio are important water-borne pathogens causing substantial morbidity and mortality in cirrhotic patients in Taiwan, but the differences in clinical manifestations of Aeromonas and Vibrio bacteremia have not been reported in detail.MethodsFrom January 2003 to September 2013, cirrhotic patients with monomicrobial Aeromonas or Vibrio bacteremia at a medical center in Taiwan were included in this study.ResultsThe study population consisted of 77 cirrhotic patients with Aeromonas bacteremia and 48 patients with Vibrio bacteremia. Both pathogens clustered during the summer season; Vibrio bacteremia was more correlated with higher temperatures (Vibrio: r2 = 0.95, p

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1-1.9 μm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging - computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation.

NRAGE, a neurotrophin receptor-interacting melanoma antigen-encoding gene homolog, is significantly increased in the nucleus of radioresistant esophageal tumor cell lines and is highly upregulated to promote cell proliferation in esophageal carcinomas (ECs). However, whether the overexpressed NRAGE promotes cell growth by participating in DNA-damage response (DDR) is still unclear. Here we show that NRAGE is required for efficient double-strand breaks (DSBs) repair via homologous recombination repair (HRR) and downregulation of NRAGE greatly sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover, NRAGE not only regulates the stability of DDR factors, RNF8 and BARD1, in a ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1 and RNF8 via their RING domains to form a novel ternary complex. Additionally, the expression of NRAGE is closely correlated with RNF8 and BARD1 in esophageal tumor tissues. In summary, our findings reveal a novel function of NRAGE that will help to guide personalized esophageal cancer treatments by targeting NRAGE to increase cell sensitivity to DNA-damaging therapeutics in the long run.

Process research and development of the fully synthetic broad spectrum tetracycline TP-2758, with a chiral pyrrolidine side chain at the C-8 position, is described. The process utilizes two key intermediates, 7 and 10, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclinical and early clinical development. The pyrrolidine moiety was introduced into the left-hand piece (LHP) 10 with high enantioselectivity using Ellman’s sulfinamide chemistry, and the absolute configuration was confirmed by X-ray crystal structure analysis.

Menstrual pain is the most prevalent gynecological complaint, and is usually without organic cause (termed primary dysmenorrhea, PDM). The high comorbidity in the later life of PDM with many functional pain disorders (associated with central dysfunction of pain inhibition, eg, fibromyalgia) suggests possible maladaptive functionality of pain modulatory systems already occurred in young PDM women, making them vulnerable to functional pain disorders. Periaqueductal gray (PAG) matter functions as a critical hub in the neuraxis of pain modulatory systems; therefore, we investigated the functional connectivity of PAG in PDM. Forty-six PDM subjects and 49 controls received resting-state functional magnetic resonance imaging during menstruation and periovulatory phases. The PAG of PDM subjects exhibited adaptive/reactive hyperconnectivity with the sensorimotor cortex during painful menstruation, whereas it exhibited maladaptive hypoconnectivity with the dorsolateral prefrontal cortex and default mode network (involving the ventromedial prefrontal cortex, posterior cingulate cortex, or posterior parietal cortex) during menstruation or periovulatory phase. We propose that the maladaptive descending pain modulatory systems in PDM may underpin the central susceptibility to subsequent development of various functional disorders later in life. This hypothesis is corroborated by the growing body of evidence that hypoconnectivity between PAG and default mode network is a coterminal to many functional pain disorders.

Background Hinokiol is a naturally occurring diterpenoid compound isolated from plants such as Taiwania cryptomerioides . Anti-oxidation, anti-cancer, and anti-inflammation effects of this compound have been reported. It is not yet known if hinokiol affects neurons or neuronal ion channel activities. We reported here that hinokiol inhibited voltage-gated Na + channels (VGSC) in neuronal cells and we characterized the mechanisms of block. Methods The effects of hinokiol on Na + channels were examined using the voltage-clamp (whole-cell mode) technique. Results VGSC was blocked by hinokiol in a concentration-dependent and state-dependent manner in neuroblastoma N2A cells: IC 50 are 11.3 and 37.4 μM in holding potentials of −70 and −100 mV, respectively. In the presence of hinokiol there was a 13-mV left shift in steady-state inactivation curves; however, activation gating was not altered. VGSC inhibition by hinokiol did not require channel opening and was thus considered to be closed-channel block. In the presence of hinokiol, since the degree of block did not enhance with stimulation frequency, block by hinokiol thus did not exhibit use-dependence. Recovery from channel inactivation was not significantly affected in the presence of hinokiol. In addition, hinokiol also inhibited VGSC of differentiated neuronal NG108-15 cells and rat hippocampal CA1 neurons. Conclusion Our results therefore suggest hinokiol inhibited VGSC in a closed-channel block manner and such inhibition involved intensification of channel inactivation.

This paper demonstrates the development of an automatic mobile trainer employing inertial movement units (IMUs). The device is inspired by Neuro-Developmental Treatment (NDT), which is an effective rehabilitation method for stroke patients that promotes the relearning of motor skills by repeated training. However, traditional NDT training is very labor intensive and time consuming for therapists, thus, stroke patients usually cannot receive sufficient rehabilitation training. Therefore, we developed a mobile assisted device that can automatically repeat the therapists&rsquo, intervention and help increase patient training time. The proposed mobile trainer, which allows the users to move at their preferred speeds, consists of three systems: the gait detection system, the motor control system, and the movable mechanism. The gait detection system applies IMUs to detect the user&rsquo, s gait events and triggers the motor control system accordingly. The motor control system receives the triggering signals and imitates the therapist&rsquo, s intervention patterns by robust control. The movable mechanism integrates these first two systems to form a mobile gait-training device. Finally, we conducted preliminary tests and defined two performance indexes to evaluate the effectiveness of the proposed trainer. Based on the results, the mobile trainer is deemed successful at improving the testing subjects&rsquo, walking ability.

Eosinophilic annular erythema (EAE) is a rare eosinophilic dermatosis with few documented cases in the literature. It is considered either a distinct entity or subtype of Well’s syndrome (eosinophilic cellulitis), but EAE, in contrast to Well’s syndrome, is characterized by a chronic course and resistance to treatment. Therapies with reported efficacy include anti-malarial medications, suplatast tosilate, and dapsone. We report the first adult case of EAE to respond to dupilumab, an IL-4 receptor antagonist, which targets the type 2 inflammatory response associated with tissue eosinophilia.

Aims This paper aims to systematically review the illness perceptions of stroke patients and to examine the association between illness representation and psychological distress in empirical research studies. Background Patients’ perceptions of health threats determine their coping behavior. Several recent studies have focused on illness belief and distress in stroke patients. This information is suitable for a meta-analysis to further understand stroke patients’ illness perceptions. Design Systematic review and meta-analysis. Method An electronic literature search was conducted using the CINAHL, MEDLINE, PubMed, Cochrane library, and Google Scholar databases. Search strategies were title (stroke or cerebrovascular accident or CVA or cerebral vascular event or transient ischemic attack or TIA) and keyword (disease or illness) and keyword (perceptions or attitudes or opinion or experience or view or reflection or beliefs). The literature search covers the period of January 1990 to October 2018. Seven articles were included in the meta-analysis and Fisher’s z was calculated with correlation coefficient or regression coefficient values for eight illness representation dimensions and psychological distress. All statistical analyses were performed using Comprehensive Meta-Analysis (CMA) version 3.0 software. Results A total of 49 studies were reviewed, and seven studies with a total of 507 participants were eligible for the meta-analysis. For patients’ perceived anxiety and depression, six of seven studies, with 285 to 461 participants, were examined in terms of the average corrected correlation coefficient across the studies. It was found that stroke patients’ perception of a strong illness identity, timeline-acute/chronic, timeline-cyclical, consequences, and emotional responses were significantly and positively related to anxiety and depression. The pooled z-value ranged from 0.189 to 0.460. Conversely, for protective-related factors, such as stroke patients’ perceived personal control, treatment control, and illness coherence, only perceived illness coherence was significantly negatively associated with depression (z-value, -0.122; 95% CI: -0.241, -0.002). For patients’ perceived overall distress, three of seven studies with 173 participants showed that there were significant and positive associations between identity, consequence, emotions, and distress (z-value ranges = 0.493–0.711) as well as a significant and negative association between illness coherence and overall distress (z-value, -0.226; 95% CI: -0.379, -0.073). Conclusion An association between illness representation and distress exists in stroke patients. Risk factors are the most significant in terms of this relationship, and protective factors do not have a protective health impact. Protection factors need to be promoted to reduce patient distress.

Volume of the urinary bladder is an important factor for diagnosis of lower urinary tract dysfunction (LUTD). Clinically, the need of urinary catheter insertion procedure is determined by the amount of residual urine inside bladder through bladder sonography. If for each time the urination volume is less than the volume inside bladder, it will increase the residual urine volume gradually. As a result, the patient fails to urinate and urinary retention is occurred. In order to release retention, it is needed to insert urinary catheter into the urinary bladder. The approach currently being used in clinical is to estimate the residual urine from ultrasound image via an equation (Volume = Length × Width × Height × 0.52), in which human efforts are required. Besides, the resulting measurement is still not accurate enough. Therefore, a solution that treat each pixel signature vector in bladder as the target signal to do classification is proposed in this paper.

This study presents a preliminary development of a robotic assistant system with its solutions for combining robotics and health-care devices. The mobile robotic system acts as the sensing equipment for monitoring the heart rate from the continuous electrocardiographic (ECG) waveforms in real-world testing. Routine ECG monitoring can aid clinic diagnoses in cardiac and non-cardiac diseases. In addition, with the aid by technical advancements in information and communication technology (ICT), the designed robot can provide the assistance in the remote symptom monitoring for end users susceptible to heart failure, and advance healthcare in terms of reducing physicians' visiting costs while maintaining the quality of care. To present the planned features of the designed robotic system with ECG monitoring and diagnosis assistance, consider an end user at home, where the experimental environment is deployed.

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.

Shear wave elastography (SWE) has been widely adopted for clinical in vivo imaging of tissue elasticity for disease diagnosis, and this modality can be a valuable tool for in vitro mechanobiology studies but its full potential has yet to be explored. Here we present a laser speckle contrast SWE system for noncontact monitoring the spatiotemporal changes of the extracellular matrix (ECM) stiffness in three-dimensional cancer cell culture system while providing submillimeter spatial resolution and temporal resolution of 10 s. The shear modulus measured was found to be strongly correlated with the ECM fiber density in two types of cell culture system (r = 0.832 with P r = 0.642 with P = 0.024 for cell culture systems containing 4 mg/ml Matrigel with 1 mg/ml and 2 mg/ml collagen type I hydrogel, respectively). Cell migration along the stiffness gradient in the cell culture system and an association between cell proliferation and the local ECM stiffness was observed. As the elasticity measurement is performed without the need of exogenous probes, the proposed method can be used to study how the microenvironmental stiffness interacts with cancer cell behaviors without possible adverse effects of the exogenous particles, and could potentially be an effective screening tool when developing new treatment strategies.

BACKGROUND Persistent massive ascites (PMAS) longer than 14 days after living donor liver transplantation is not uncommon and associated with worse outcome. A predictive risk scoring system was constructed after analysis of recipient, graft, and surgery-related factors. METHODS We retrospectively reviewed adult living donor liver transplantation recipients from 2005 to 2011 after excluding cases that experienced any intervention for perioperative vascular-related events. Two groups were identified, PMAS and non-PMAS. The score was constructed from significant factors using weighted odds ratios (OR). RESULTS The study population included 439 recipients. Persistent massive ascites was evident in 74 cases (17%). Five significant risk predictors were identified in multivariate analysis: pretransplant serum creatinine greater than 1.5 mg/dL (OR, 5.693; weighted OR, 2), recipient spleen to graft volume ratio greater than 1.3 (OR, 4.466; weighted OR, 2), left lobe graft (OR, 3.196; weighted OR, 1), more than 1000 mL ascites at laparotomy (OR, 2.541; weighted OR, 1), and graft recipient weight ratio less than 0.8 (OR, 2.419; weighted OR, 1). The clinical scoring system was constructed and ranged from 0 to 7. Receiver operating characteristic analysis showed an area under the curve (0.778, P < 0.001). Internal validation of the score showed an area under the curve of 0.783. The 5- and 10-year survival rates for the non-PMAS versus the PMAS groups were 89% and 84% versus 81% and 48%, respectively (P = 0.001). CONCLUSIONS The PMAS score is a predictive pretransplant clinical tool. A Clinical cutoff score of 4 might be decision-changing. Pretransplant correction of renal functions, deciding to harvest a large graft and/or consideration of splenic artery embolization could reduce the risk of PMAS.

Aim Mood disorders are a serious issue for patients with rheumatoid arthritis (RA) because poor mental health can exacerbate the disease course. This study aimed to identify the effect of proinflammatory cytokines on the mood of patients with RA. Methods This study was conducted at a rheumatology clinic in Northern Taiwan. In total, 113 patients with RA and 42 healthy controls were assessed for anxiety and depression symptoms using Hospital Anxiety and Depression Scale (HADS). RA was assessed using the Disease Activity Score of 28 joints (DAS28). Serum proinflammatory cytokine levels, including interleukin (IL)-1β, IL-6, IL-17 and tumor necrosis factor alpha (TNF-α) were measured and compared between different patient groups according to disease activity and pain level. Results Serum IL-1β, IL-6, IL-17 and TNF-α levels were significantly higher in patients with RA than in healthy controls, as were the mean anxiety and depression subscale scores. In patients with RA who had different disease activities, pain severity correlated with both anxiety and depression symptoms. When HADS scores were analyzed according to pain levels, age was correlated with depression in the severe pain group. In the mild pain group, patients with higher IL-6 or higher IL-17 had a higher risk of depression. There was no correlation between mood symptoms and cytokine levels in healthy controls. Conclusion Elevated serum IL-6 and IL-17 levels in patients with RA induce arthritis and cause mood symptoms, especially depression symptoms.

Background Few studies have investigated the difference in bacterial contamination between conventional reused ventilator systems and disposable closed ventilator-suction systems. The aim of this study was to investigate the bacterial contamination rates of the reused and disposable ventilator systems, and the association between system disconnection and bacterial contamination of ventilator systems. Methods The enrolled intubated and mechanically ventilated patients used a conventional reused ventilator system and a disposable closed ventilator-suction system, respectively, for a week; specimens were then collected from the ventilator circuit systems to evaluate human and environmental bacterial contamination. The sputum specimens from patients were also analyzed in this study. Results The detection rate of bacteria in the conventional reused ventilator system was substantially higher than that in the disposable ventilator system. The inspiratory and expiratory limbs of the disposable closed ventilator-suction system had higher bacterial concentrations than the conventional reused ventilator system. The bacterial concentration in the heated humidifier of the reused ventilator system was significantly higher than that in the disposable ventilator system. Positive associations existed among the bacterial concentrations at different locations in the reused and disposable ventilator systems, respectively. The predominant bacteria identified in the reused and disposable ventilator systems included Acinetobacter spp., Bacillus cereus, Elizabethkingia spp., Pseudomonas spp., and Stenotrophomonas (Xan) maltophilia. Conclusions Both the reused and disposable ventilator systems had high bacterial contamination rates after one week of use. Disconnection of the ventilator systems should be avoided during system operation to decrease the risks of environmental pollution and human exposure, especially for the disposable ventilator system. Trial registration ClinicalTrials.gov PRS / NCT03359148

Human adenoviruses (HAdV) 3 and 7 can cause acute respiratory disease epidemics and outbreaks. Identification of neutralizing epitopes is vital for surveillance and vaccine development. In this study, we generated the recombinant capsid-chimeric human adenoviruses rAd3E-Fk7, containing the Ad3E backbone and the HAdV-7 fiber knob, and rAd3E-H7Fk7, which contain an Ad3E backbone but HAdV-7 hexon and fiber knob. In vitro neutralization tests with these chimeric adenoviruses using both mouse and human antisera indicated that hexon and fiber knob are the major targets recognized by neutralizing antibodies against HAdV-3 or HAdV-7, and other capsid proteins including the penton base and fiber shaft may not contribute to neutralizing antibody responses. In conclusion, both hexon and fiber knob structures in HAdV-3 and HAdV-7 may be the proteins which induce neutralizing antibody responses and thus may be important for adenovirus vaccine and drug development.

Background/Aim: Pterygium is composed of proliferating fibrovascular tissue, and its formation and progression are closely related to the homeostasis of the extracellular microenvironment. However, few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnostic or prognostic potential in pterygium. In this study, we investigated the contribution of a polymorphism in the promoter region of MMP-8 (-799C/T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to pterygium. Materials and Methods: In this study, 134 patients with pterygium and 268 non-cancer controls patients were collected and the MMP-8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes of each subject were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The results showed that the three polymorphisms investigated were not significantly associated with risk of pterygium. In addition, the stratified analysis showed that there was no interaction between MMP-8 genotype with age or gender on pterygium risk determination. Conclusion: Polymorphisms at MMP-8 -799C/T, Val436Ala and Lys460Thr may not mainly contribute to determining personal susceptibility to pterygium in the Taiwanese examined.

Primary dysmenorrhea (PDM), cyclic menstrual pain in the absence of pelvic anomalies, is one of the most common gynecological disorders in reproductive females. Classified as chronic pelvic pain syndrome, PDM encompasses recurrent spontaneous painful ("on") and pain-free ("off") states and is thus a good clinical model to study state- and trait-related changes of pain in the brain. In this chapter, we summarize state-of-the-art neuroimaging studies of primary dysmenorrhea from phenotype and endophenotype to genotype facets. Structural and functional brain alterations associated with primary dysmenorrhea are discussed.

Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC) cytosolic Ca(2+) concentration ([Ca(2+)]i) and is of prime importance in vascular tone regulation as NO relaxes vascular smooth muscle. Agonists could stimulate EC [Ca(2+)]i elevation by triggering Ca(2+) influx via plasma membrane ion channels, one of which is the store-operated Ca(2+) channel; the latter opens as a result of agonist-triggered internal Ca(2+) release. Endotoxin (lipopolysaccharide, LPS) could cause sepsis, which is often the fatal cause in critically ill patients. One of the LPS-induced damages is EC dysfunction, eventually leading to perturbations in hemodynamics. We obtained data showing that LPS-challenged mouse cerebral cortex endothelial bEND.3 cells did not suffer from apoptotic death, and in fact had intact agonist-triggered intracellular Ca(2+) release; however, they had reduced store-operated Ca(2+) entry (SOCE) after LPS treatment for 3h or more. Using real-time PCR, we did not find a decrease in gene expression of stromal interaction molecule 1 (STIM1) and Orai1 (two SOCE protein components) in bEND.3 cells treated with LPS for 15h. LPS inhibitory effects could be largely prevented by sodium salicylate (an inhibitor of nuclear factor-κB; NF-κB) or SB203580 (an inhibitor of p38 mitogen-activated protein kinases; p38 MAPK), suggesting that the p38 MAPK-NF-κB pathway is involved in SOCE inhibition.

The underlying mechanisms for the action of caramiphen used in local anesthesia are not well understood. The purpose of this study was to evaluate the block of caramiphen on voltage-gated Na⁺ channels and in spinal anesthesia. We investigated the effect of caramiphen on voltage-gated sodium channels in differentiated neuronal NG108-15 cells as well as on rat motor function, proprioception, and pain behavior (when administered intrathecally). In in vitro experiments, lidocaine produced concentration- and state-dependent effects on tonic block of voltage-gated Na⁺ currents (IC₅₀ of 66.2 and 212.9 µM at holding potentials of -70 and -100 mV, respectively). Caramiphen exhibited a milder state-dependence of block (IC₅₀ of 52.1 and 99.5 µM at holding potentials of -70 and -100 mV, respectively). Lidocaine showed a much stronger frequency-dependence of block than caramiphen: with high frequency stimulation (3.33 Hz), 50 µM caramiphen elicited an additional 20% blockade, whereas the same concentration of lidocaine produced 50% more block. In in vivo experiments, caramiphen with a more sensory-selective action over motor blockade was more potent than lidocaine (P

Objective: This study evaluated the effectiveness of a 10-week exercise intervention in reducing depression and fatigue in women with postpartum depression. Design: A one-group pretest/ posttest quasi-experiment was conducted. Setting: A postpartum ward in a medical center in Taipei city was used. Participants: Nineteen women at 7 - 12 weeks postpartum with an Edinburgh Postnatal Depression Scale score ≥ 9 were recruited. Methods: The women participated in a postpartum exercise support program 1 hour per week for 10 weeks. The program was led by a professional coach; it integrated yoga, Pilates, elastic band exercise, low-intensity aerobics, and motherhood role experience sharing. Results: After the postpartum exercise support program intervention, depression scores decreased from 10.4 ± 3.29 to 7.80 ± 2.73 (t = 3.632, P = 0.003); fatigue scores decreased from 8.73 ± 5.02 to 5.40 ± 3.89 (t = 2.988, P = 0.010). Conclusion: PESP administered to women with postpartum depression appeared to benefit their psychological wellbeing.

Many studies indicate that circulating microRNAs (miRNAs) could play important roles in screening human cancers, including colorectal cancer (CRC). However, the conflicting results on the accuracy of miRNA detection lead us to conduct this meta-analysis to access the predictive value of miRNAs for predicting CRC. Eligible studies were identified from the Medline, Embase, CNKI, and Web of Science by the search strategies and screening criterion. We used random effects models to calculate the pooled results from studies. The summary receiver operator characteristic curve (SROC) and the area under the SROC curve (AUC) were used to estimate the predictive accuracy. Subgroup analyses and meta-regression were used to analyze potential sources of heterogeneity. We used Deeks’ funnel plot asymmetry test to test publication bias. This meta-analysis included a total of 24 studies from 19 articles, including 1558 CRC patients and 1085 controls. The overall pooled results from the meta-analysis were as follows: sensitivity was 0.81 (95 % confidence interval (CI) 0.77–0.85), specificity was 0.84 (95 % CI 0.78–0.88), PLR was 5.0 (95 % CI 3.5–6.9), NLR was 0.22 (95 % CI 0.18–0.28), DOR was 23 (95 % CI 14–37), and AUC was 0.89 (95 % CI 0.86–0.91). Subgroup and meta-regression analyses demonstrated that multiple miRNAs (AUC, sensitivity, and specificity of 0.92, 0.84, and 0.87, respectively) had a higher predictive accuracy than single miRNA (AUC, sensitivity, and specificity of 0.84, 0.78, and 0.78, respectively). In addition, we found that serum can be a better matrix for miRNA assays in screening CRC compared with plasma. In summary, our data suggests that circulating miRNAs, particularly multiple miRNAs, which have higher accuracy than single miRNAs, are excellent biomarker for screening CRC with good sensitivity and noninvasive nature.

To provide continuous, accessible, and quality care, a diabetes share-care program has been in place in Taiwan for several years. Lukang Christian Hospital, a member of the diabetes share-care network, endeavors to provide "patient-centered" care aimed at increasing care quality and reducing diabetic complications. Information technology has been employed by the hospital for monitoring care quality and analyzing cost-effectiveness. Structured health-care programs have also been developed to ensure the completeness of diabetes care and to encourage self-management of individuals at high risk for diabetes. The implementation of these strategies has led to progressive improvement in quality measures and spawned novel and creative ways to deliver care services.

Background Human bocavirus 1 (HBoV1) is an important cause of acute respiratory illness (ARI), yet the epidemiology and effect of meteorological conditions on infection is not fully understood. To investigate the distribution of HBoV1 and determine the effect of meteorological conditions, hospitalized pediatric patients were studied in a subtropical region of China. Methods Samples from 11,399 hospitalized pediatric patients (≤14 years old), with ARI were tested for HBoV1 and other common respiratory pathogens using real-time PCR, between July 2009 and June 2016. In addition, local meteorological data were collected. Results Of the 11,399 patients tested, 5606 (49.2%) were positive for at least one respiratory pathogen. Two hundred forty-eight of 11,399 (2.2%) were positive for HBoV1 infection. Co-infection was common in HBoV1-positive patients (45.2%, 112/248). A significant difference in the prevalence of HBoV1 was found in patients in different age groups (p

Mechanobiology is an emerging field of research that studies the influences on the cell behaviors by mechanical stimuli. In this research, the previously developed laser speckle contrast shear wave imaging system is implemented for monitoring the temporal and spatial changes in the stiffness of the self-designed in vitro cancer metastasis model. Results from the immunostaining with laminin and collagen type I are analyzed to provide information about the changes of the cell culture matrix, in correlation with the mechanical measurements. The variations of shear wave speed measurements are highly correlated with the changes in the content of the cell culture matrix. Thus, quantitative measurement of the stiffness of the extracellular matrix may provide information about the matrix remodeling process during cancer progression, which may lead to the improvements in the cancer treatment strategy.

This study retrospectively investigated the effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) on long-term outcome of lung adenocarcinoma patients with malignant pleural effusion (MPE). We identified 52 patients with lung adenocarcinoma harboring activating EGFR gene mutation who had symptomatic MPE at initial diagnosis and received EGFR-TKI as first-line treatment from Taipei Medical University Hospital (Taipei, Taiwan) database. Pleural progression-free survival (PPFS) was defined as the time from administration of EGFR-TKI to the first observation of pleural progression requiring therapeutic thoracentesis or death from any cause. The median duration of follow-up was 14.9 months (range 1.0-72.0 months). The overall pleural objective response rate was 94%, and the median tumor progression free survival and median PPFS was 10.2 (95% CI 7.1-12.8 months) and 13.1 months (95% CI 10.2-15.3 months), respectively. The difference in PPFS between EGFR exon 19 deletion (n = 23) and L858R mutation (n =29) groups was not statistically significant (p = 0.651). Thirty-six patients (69%) remain pleural progression-free during the whole disease course. EGFR-TKI was highly effective for malignant pleural effusion in patients with lung adenocarcinoma harboring activating EGFR mutation. It merits further prospective trial comparing EGFR-TKI alone with EGFR-TKI plus angiogenesis inhibitor in treatment of malignant pleural effusion with mutated EGFR.