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This article presents a programmable multiple frequencies clock generator with a process and temperature compensation circuit design. The proposed clock generator can achieve a stable and wide frequency range output for a single input frequency by using digital control codes as well as process and temperature compensation mechanisms. In our approach, the first step is to adjust the duty-cycle of the input clock by using a digitally controlled pulsewidth modulator (DCPWM) to generate an output clock signal with a duty-cycle of 20% to 80%. Second, the various duty-cycle clock outputs of the DCPWM are integrated by the duty-cycle-to-voltage converter to generate analog voltage signals to control the succeeding voltage-controlled ring oscillator (VCO). Through the use of various control voltages, different VCO output frequencies are generated. Finally, by using the process and temperature compensation circuit, the proposed clock generator can provide a stable and wide frequency range. The proposed chip is fabricated in a 180-nm CMOS process and has an output frequency range of 35–138 MHz at a supply voltage of 0.9 V. At 120 MHz, the power dissipation and rms jitter are 224.3 μW and 7.84 ps, respectively. The active area of the chip is 0.62 mm × 0.76 mm.

Air pollution has become a major concern worldwide. Many epidemiological studies have proved relationships between fine particulate matter (PM2.5) and various diseases, but most studies only use short-term and models for specific groups to derive relationships with acute diseases. This makes it difficult to understand long-term exposure, nonlinear relationships, and spatial-temporal health risks regarding chronic diseases. Therefore, this study proposed to analyze and map PM2.5 exceedance probability from long-term spatial-temporal monitoring data using radial basis function estimation. We then constructed and compared multiple linear regression and generalized additive models to investigate linear and nonlinear relationships between long-term average PM2.5 concentration, PM2.5 potential probability for exceeding the standard, and standardized mortality for the top ten causes of death in all towns and villages in Taiwan nationally from 2010 to 2017. Linear models indicate that increasing PM2.5 concentration increased malignant neoplasm, pneumonia, and chronic lower respiratory disease mortalities; chronic liver diseases; and cirrhosis; whereas heart diseases and esophagus cancer mortality decreased. For the nonlinear model results, it can be found that there were also significant nonlinear relationships between PM2.5 concentration and malignant mortalities for neoplasm, heart disease, diabetes; and trachea, bronchus, lung, liver, intrahepatic bile duct, and esophagus cancer. Thus, long-term exposure to PM2.5 may be a significant risk factor for multiple acute and chronic diseases. Results from this study can be directly applied worldwide to provide air quality and health management references for governments, and important information on long-term health risks for local residents in the study area.

Background Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials. Objective To determine the best first-line steroid-sparing adjuvants for pemphigus treatment. Methods Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose. Results Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, −11,830.5 mg (95% CI, −14,089.48 to −9571.52), −3032.48 mg (−4700.74 to −1364.22), and −2469.54 mg (−4128.42 to −810.66), respectively. Limitations The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons. Conclusion Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.

Background: Increasing the vertical dimension of occlusion (VDO) is a common procedure in complicated prosthodontic treatment. The swallowing technique had been verified as a functional method to determine the VDO. The purpose of this study was to investigate the association between increasing VDO and mandibular movement during swallowing. Methods: 26 females and 14 males were enrolled (age range: 21 to 30 year-old). Under different increased VDO (3, 5, and 8 mm), the mandibular trajectory during swallowing was measured by K7 Evaluation System (Myotronics®). When the subjects were instructed to salivary swallowing, the range of mandibular movement in vertical, anteroposterior and lateral directions were recorded. Results: Increasing VDO significantly impacted the range of mandibular movement in lateral direction during swallowing (p

Objectives Eugenosedin-A (Eu-A), an adrenergic and serotonergic antagonist, is known to have anti-metabolic syndrome effects. In this study, we evaluated its protective effects against diabetes mellitus (DM) in spontaneous hypertensive rats (SHR) and compared it with two anti-diabetes medications, glibenclamide (Gli) and pioglitazone (Pio). Methods We divided 10-week-old SHRs into five groups: a control group fed a normal diet; an untreated DM group induced by injecting the SHRs with STZ/NA and feeding them a high-fat diet (HFD); and three treated groups (after giving STZ/NA and HFD) gavage given with Eu-A, Gli or Pio (5 mg/kg per day) for 4 weeks. Key findings The untreated DM group weighed less and had hyperglycaemia, hypoinsulinemia and hyperlipidemia. They were also found to have aberrant glucose-dependent insulin pathways, glucose metabolism and lipid synthesis proteins, while the controls did not. Eu-A, Gli and Pio ameliorated the above biochemical parameters in the treatment groups. Eu-A and Pio, but not Gli, improved hypertension and tachycardia. Conclusions Taken together, Eu-A ameliorated DM, hypertension and tachycardia by improving glucose, lipid homeostasis and anti-adrenergic, serotonergic activities. We concluded that Eu-A could be used in the development of an effective agent for controlling DM and its complications.

Mei-Chun Yeh,1 Ben J Wu,1 Yue Li,1 Mina Elahy,1 Leonel Prado-Lourenco,1 Jim Sockler,2 Herman Lau,3 Ric O Day,4 Levon M Khachigian1 1Vascular Biology and Translational Research, School of Medical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, 2052, Australia; 2Statistical Operations & Programming, Datapharm Australia Pty Ltd, Drummoyne, NSW, 2047, Australia; 3BJC Health, Chatswood, NSW, 2067, Australia; 4Department of Clinical Pharmacology & Toxicology, Therapeutics Centre, St Vincent’s Hospital, UNSW Medicine and Health, Darlinghurst, NSW, 2010, AustraliaCorrespondence: Levon M KhachigianVascular Biology and Translational Research, School of Medical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, 2052, AustraliaTel +61 2 9385 2537Email L.Khachigian@unsw.edu.auIntroduction: Inflammation and bone erosion are processes key to the pathogenesis of rheumatoid arthritis, a systemic autoimmune disease causing progressive disability and pain, impacting around 1.3 million people in the United States alone. However, many patients do not respond sufficiently to existing therapies or benefit is not sustained and alternate therapeutic approaches are lacking. We recently identified the dibenzoxazepinone BT2, which inhibits ERK phosphorylation, from a high-throughput chemical screen and identified its ability to inhibit angiogenesis and vascular leakiness.Methods: Here we evaluated BT2 for potential anti-inflammatory activity in in vitro models of human monocytic-endothelial cell adhesion, monocytic cell extravasation and collagen antibody-induced arthritis in mice.Results: BT2 inhibits human monocytic cell adhesion to IL-1ß-treated human endothelial cells and inhibits monocytic transendothelial migration toward MCP-1. In mice rendered arthritic, single systemic administration of BT2 prevented footpad swelling, bone destruction and TRAP+ cells in the joints. BT2 suppressed inducible circulating levels of IL-1ß, IL-2 and IL-6 to normal levels without affecting levels of IL-4 or IL-10 among other cytokines. BT2 also inhibited the expression of pro-inflammatory adhesion molecules ICAM-1 and VCAM-1 in arthritic joints. There was no evidence of toxicity following intraperitoneal, gavage or intraarticular administration of BT2.Conclusion: BT2 is a novel small molecule inhibitor of joint inflammation, bone erosion, pro-inflammatory cytokine and adhesion molecule expression. This suggests the potential clinical utility of BT2 as a new anti-inflammatory agent.Keywords: inflammation, pathology, bone erosion, rheumatoid arthritis, dibenzoxazepinone

This study increases the strength of a honeycomb structure under a static load using an innovative and integrated multi-objective optimization procedure. Using a uniform design of experiment, a gro...

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

Siglecs, sialic acid (SA)-binding immunoglobulin (Ig)-like lectins, belong to a family of Ig-like lectins. All Siglecs have at least two domains including an extracellular domain with variable (V) and constant (C)-set immunoglobulin (Ig) regions, and a transmembrane domain. Some of the Siglecs (Siglec-2-12, -17, -E, -F and -G) with three domains including immunoreceptor tyrosine-based inhibitory motif associated with Src homology 2 (SH2) tyrosine phosphatases (SHP1/2) usually deliver an inhibitory signal. Certain Siglecs (Siglec-14, -15, -16 and -H) containing no intracellular domain carry certain basic amino acid in transmembrane domain coupled with immunoreceptor tyrosine-based activating motif for cell activation. The number of Siglec-encoding genes has been correlated to lifespan of mammals, indicating its evolutional advantage on acquisition of Siglecs in humans. Certain polymorphisms of Siglecs have been associated with premature delivery, infection, schizophrenia, allergy, dementia or chronic obstructive pulmonary disease. Siglecs mainly expressing on leukocytes could interact with cis- or trans-SA ligands for cell-cell and host-organism interactions on infections, inflammations and cancers. Amplifying or eliminating the SA-Siglec interactions is a promising strategy to treat cancers, infections and inflammations, based on SA modifications in different linkages or nanoparticle decoration, and on the antibodies in conjugation of chimeric receptor design or toxins.

AIM The aim of this study was to investigate the associations between candidate gene variants and domains of neuropsychiatric symptoms (NPS) and the changes in these associations over a 1-year period. METHODS Seven hundred and ninety-three Taiwanese participants (47.8% female) with Alzheimer's disease (AD) were enrolled. Genes associated with a risk of developing AD were selected as candidate genes. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), and the NPI-Q total score and sub-scores for the Psychosis, Mood, and Frontal Syndrome domains were calculated. RESULTS Patients with AD and the APOE e4 allele exhibited more obvious symptoms of psychosis. Mood symptoms were associated with CD33 rs3865444 and EPHA1 rs11767557, and frontal symptoms were associated with SORL1 rs3824968. A 1-year Time × Alleles interaction effect of CD33 rs3865444 on mood symptoms was discerned. CONCLUSION Risk genes of AD, which are also associated with NPS, are APOE e4 for psychosis, CD33 and EPHA1 for mood symptoms, and SORL1 for frontal symptoms. The association between CD33 and mood symptoms is dynamic and could change over 1 year; however, the results should be interpreted with caution because corrections for multiple comparisons were not performed.

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

PurposeChimeric antibody Miltuximab®, a human IgG1 engineered from the parent antibody MIL-38, is in clinical development for solid tumour therapy. Miltuximab® targets glypican-1 (GPC-1), a cell surface protein involved in tumour growth, which is overexpressed in solid tumours, including prostate cancer (PCa). This study investigated the potential of89Zr-labelled Miltuximab® as an imaging agent, and177Lu-labelled Miltuximab® as a targeted beta therapy, in a mouse xenograft model of human prostate cancer.MethodsMale BALB/c nude mice were inoculated subcutaneously with GPC-1-positive DU-145 PCa cells. In imaging and biodistribution studies, mice bearing palpable tumours received (a) 2.62 MBq [89Zr]Zr-DFO-Miltuximab® followed by PET-CT imaging, or (b) 6 MBq [177Lu]Lu-DOTA-Miltuximab® by Cerenkov imaging, and ex vivo assessment of biodistribution. In an initial tumour efficacy study, mice bearing DU-145 tumours were administered intravenously with 6 MBq [177Lu]Lu-DOTA-Miltuximab® or control DOTA-Miltuximab® then euthanised after 27 days. In a subsequent survival efficacy study, tumour-bearing mice were given 3 or 10 MBq of [177Lu]Lu-DOTA-Miltuximab®, or control, and followed up to 120 days.ResultsAntibody accumulation in DU-145 xenografts was detected by PET-CT imaging using [89Zr]Zr-DFO-Miltuximab® and confirmed by Cerenkov luminescence imaging post injection of [177Lu]Lu-DOTA-Miltuximab®. Antibody accumulation was higher (% IA/g) in tumours than other organs across multiple time points. A single injection with 6 MBq of [177Lu]Lu-DOTA-Miltuximab® significantly inhibited tumour growth as compared with DOTA-Miltuximab® (control). In the survival study, mice treated with 10 MBq [177Lu]Lu-DOTA-Miltuximab® had significantly prolonged survival (mean 85 days) versus control (45 days), an effect associated with increased cancer cell apoptosis. Tissue histopathology assessment showed no abnormalities associated with [177Lu]Lu-DOTA-Miltuximab®, in line with other observations of tolerability, including body weight stability.ConclusionThese findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([89Zr]Zr-DFO-Miltuximab®) and a beta therapy ([177Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours.

Heavy rainfall and strong wind are the two main sources of disasters that are caused by tropical cyclones (TCs), and typhoons with different characteristics may induce different agricultural losses. Traditionally, the classification of typhoon intensity has not considered the amount of rainfall. Here, we propose a novel approach to calculate the typhoon type index (TTI). A positive TTI represents a “wind type” typhoon, where the overall damage in a certain area from TCs is dominated by strong wind. On the other hand, a negative TTI represents a “rain type” typhoon, where the overall damage in a certain area from TCs is dominated by heavy rainfall. From the TTI, the vulnerability of crop losses from different types of typhoons can be compared and explored. For example, Typhoon Kalmaegi (2008) was classified as a rain-type typhoon (TTI = −1.22). The most affected crops were oriental melons and leafy vegetables. On the contrary, Typhoon Soudelor (2015) was classified as a significant wind-type typhoon in most of Taiwan (TTI = 1.83), and the damaged crops were mainly bananas, bamboo shoots, pomelos, and other crops that are easily blown off by strong winds. Through the method that is proposed in this study, we can understand the characteristics of each typhoon that deviate from the general situation and explore the damages that are mainly caused by strong winds or heavy rainfall at different locations. This approach can provide very useful information that is important for the disaster analysis of different agricultural products.

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

Context Evidence has shown that essential nutrients are highly correlated with the occurrence of esophageal cancer (EC). However, findings from observational studies on the associations between dietary carbohydrate, salt consumption, and the risk of EC remain controversial. Objective The aim of this study was to conduct a systematic review and meta-analysis to confirm the associations of dietary carbohydrate and salt consumption with EC risk. Data Source Various electronic databases (PubMed, MEDLINE, Embase, Google Scholar, Cochrane Library, Chinese Electronic Periodical Services, and China Knowledge Resource Integrated) were searched up until January 31, 2019. Data Extraction Data related to patient characteristics and study characteristics were extracted by 2 independent reviewers. The risk ratio reported as relative risk (RR) or odds ratio (OR) was extracted, and random-effects models were performed to estimate the summary risk ratio. Results In total, 26 studies were included in this analysis, of which 12 studies, including 11 case-control studies and 1 cohort study, examined dietary carbohydrates, and 18 studies, including 16 case-control studies and 2 cohort studies, examined dietary salt. The pooled OR showed that dietary carbohydrate intake was inversely related to EC risk (OR = 0.62; 95% confidence interval [CI], 0.50–0.77), but positive correlations between dietary salt intake and the risk of EC were supported by the recruited case-control studies (OR = 1.97; 95% CI, 1.50–2.61) and cohort studies (RR = 1.04; 95% CI, 1.00–1.08). Conclusions Salt is an essential nutrient for body functions and biochemical processes. Providing health education and management regarding proper use of salt in daily foods and labeling the amount of sodium in manufactured products to reduce the risk of developing EC should be more appropriately performed in the general population.

Background Alpha-asymmetry neurofeedback (ALAY) was applied to patients with major depressive disorder (MDD) based on the theory of frontal alpha asymmetry. Neurophysiological studies have found a higher high-beta activity of electroencephalography (EEG) at the posterior cortex among patients with comorbid MDD and anxiety symptoms. The present study examined the effects of ALAY and high-beta down-training (Beta) neurofeedback in symptoms of depression and anxiety and EEG parameters. Method Eighty-seven patients with comorbid MDD and anxiety symptoms were allocated to the ALAY, Beta, or control groups. Both neurofeedback groups received ten-session neurofeedback. All participants completed the Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), and five minutes resting EEG recording at pre-test and post-test. EEG raw signals were transformed into an A1 score [log (F4 alpha) - log (F3 alpha)], P3 and P4 high-beta power. Results BDI-II and BAI scores decreased at post-test in both ALAY and Beta groups, but no significant difference between the two groups. No significant interaction effect in A1 score at pre-test and post-test between the ALAY, Beta, and control groups. The P3 high-beta was significantly decreased in the Beta group, an increase in the control group, and no change in the ALAY group at post-test compared to the pre-test. Conclusions Both neurofeedback groups decreased symptoms of depression and anxiety. The Beta group was more effective in decreasing high-beta power at the parietal cortex compared to other groups. This non-invasive psychological intervention can be used in the future for patients with comorbid MDD and anxiety symptoms.

Background: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis–related complications such as portal hypertension (pHTN). This study compared the outcomes of metastatic breast cancer in patients with imaging-diagnosed pseudocirrhosis with or without pHTN. Methods: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Clinical pHTN was defined based on endoscopic evidence of esophageal or gastric varices. Results: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)–positive and human epidermal growth factor receptor 2 (HER2)–negative breast cancer. In total, 81 (76%) had initial metastases in both hepatic lobes, 91 (86%) had 4 or more liver metastases, and 32 (30%) had pHTN. The median overall survival (OS) was 5 and 13 months in patients with and without pHTN, respectively (p = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative breast cancer was 16, 9, and 2 months, respectively (p = .001). Patients with pHTN generally had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with pHTN had OS exceeding 1 year. In multivariate analysis, pHTN (p = .007) and triple-negative breast cancer (p = .013) were associated with poor OS. Conclusions: For patients with pseudocirrhosis, clinical pHTN was associated with liver cirrhosis–related complications and shorter median OS. A few patients with pHTN had prolonged OS with effective systemic treatment and aggressive supportive care.

BACKGROUND Gastric bypass (GB) and sleeve gastrectomy (SG) were found to achieve different remission rates in the treatment of type 2 diabetes (T2DM). The alteration in several gut hormones after bariatric surgery has been demonstrated to play a key role for T2DM remission. Nevertheless, amylin, one of the diabetes-associated peptides, so far has an undetermined position on T2DM remission after bariatric surgery. METHODS Sixty eligible patients with T2DM (GB, 30; SG, 30) were initially enrolled in the hospital-based randomized trial. Twenty patients (GB, 10; SG, 10) who met the inclusion criteria and agreed to undergo 75-g oral glucose tolerance test (OGTT) were recruited. The recruited subjects underwent anthropometric measurements, routine laboratory tests, and 75-g OGTT before and 1 year after bariatric surgery. Enzyme immunoassays for plasma amylin were analyzed. RESULTS All subjects that underwent GB and half of those who underwent SG achieved T2DM remission. Plasma amylin levels significantly decreased 60-90 min after OGTT in the GB group (p < 0.05) and 30-60 minutes after OGTT in the SG group (p < 0.05). Significantly decreased plasma amylin levels were observed at 30-90 minutes after OGTT in the noncomplete remitters of the GB group (p < 0.05). Plasma amylin levels initially increased (p < 0.05) within 30 minutes after OGTT and then decreased (p < 0.05) in the next 30-minute interval in the nonremitters of the SG group. CONCLUSION Postoral glucose challenge amylin levels could be as one of the parameters to evaluate T2DM remission after bariatric surgery, especially in those after SG.

Background: The A-Line Autoregressive Index (AAI), which is derived from auditory evoked potentials, has been used for determining anesthetic depth. This study verified the correlation between AAI values and the corresponding end-tidal concentrations of sevoflurane during general anesthesia induction. Methods: Thirty young male adults undergoing elective minor orthopedic surgery were sequentially allocated to receive inspiratory 3%, 5%, or 6% sevoflurane for mask induction, followed by mechanical ventilation after tracheal intubation. The inspiratory, end-tidal and estimated jugular bulb concentrations of sevoflurane were recorded at three target AAI values: below 20, below 10, and at the start of burst suppression. Results: The mean time to loss of consciousness in the 6% sevoflurane group was shorter than that in the 5% and 3% groups, however, the groups had comparable AAI values (range: 16–45). The 6% group had a higher end-tidal concentration (4.5% ± 0.2% vs. 3.8% ± 0.2%, p &lt, 0.05) than did the 5% group, despite having the same target anesthetic levels by AAI score ≤10, whereas the estimated jugular bulb concentrations were comparable (1.9% vs. 1.9%) in both groups. Conclusions: Following mechanical ventilation with inspiratory 3%, 5%, or 6% sevoflurane, the end-tidal concentrations were discrepant at the same end points of AAI levels, despite similar estimated jugular bulb concentrations of sevoflurane. Thus, conventional alveolar concentration may overestimate anesthesia depth during rapid wash-in of sevoflurane.

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

Knee osteoarthritis (OA) is a common degenerative articular disorder and considered one of the primary causes of pain and functional disability. Knee OA is prevalent in 10% of men and 13% of women aged 60 years above. The study aims to use cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as "scaffold," plasma rich platelet (PRP) as "signal" and chondrocytes from rat as "cell" to attenuate ACLT-induced OA progression and regenerate the knee cartilage in rats. Decellularization of the porcine cartilage was characterized by hematoxylin and eosin, 4,6-Diamidino-2-phenylindole staining, scanning electron microscopy and residual DNA quantification. The protective effect of decellularized porcine cartilage graft (dPCG) was evaluated by intra-articular administration in surgically induced anterior cruciate ligament transection (ACLT) rat osteoarthritis (OA) model. Supercritical carbon dioxide technology completely decellularized the porcine cartilage. Intra-articular administration of dPCG with or without PRP significantly reduced the ACLT-induced OA symptoms and attenuated the OA progression. Pain-relief by dPCG with or without PRP was assessed by capacitance meter and improved articular cartilage damage in the rat knee was characterized by X-ray and micro-CT. Besides, the histological analysis depicted cartilage protection by dPCG with or without PRP. The repairation and attenuation effect by dPCG with or without PRP in the articular knee cartilage damage were also explored by safranin-O, type II collagen, aggrecan and SOX-9 immuno-staining. To conclude, intra-articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model.

Objectives This study aimed to evaluate the efficacy of various local anesthesia (LA) in vital asymptomatic teeth. Materials and Methods Randomized controlled trials comparing pulpal anesthesia of various LA on vital asymptomatic teeth were included in this review. Searches were conducted in the Cochrane CENTRAL, MEDLINE (via PubMed), EMBASE, ClinicalTrials.gov, Google Scholar and 3 field-specific journals from inception to May 3, 2019. Study selection, data extraction, and risk of bias assessment using Cochrane Risk of Bias Tool were done by 2 independent reviewers in duplicate. Network meta-analysis (NMA) was performed within the frequentist setting using STATA 15.0. The LA was ranked, and the surface under the cumulative ranking (SUCRA) line was plotted. The confidence of the NMA estimates was assessed using the CINeMA web application. Results The literature search yielded 1,678 potentially eligible reports, but only 42 were included in this review. For maxillary buccal infiltration, articaine 4% with epinephrine 1:100,000 was more efficacious than lidocaine 2% with epinephrine 1:100,000 (odds ratio, 2.11; 95% confidence interval, 1.14-3.89). For mandibular buccal infiltration, articaine 4% with epinephrine 1:100,000 was more efficacious than various lidocaine solutions. The SUCRA ranking was highest for articaine 4% with epinephrine when used as maxillary and mandibular buccal infiltrations, and lidocaine 2% with epinephrine 1:80,000 when used as inferior alveolar nerve block. Inconsistency and imprecision were detected in some of the NMA estimates. Conclusions Articaine 4% with epinephrine is superior when maxillary or mandibular infiltration is required in vital asymptomatic teeth.

BACKGROUND: Doppler-guided hemorrhoid artery ligation and stapled hemorrhoidopexy have been used in surgical practices to avoid post-hemorrhoidectomy pain. Our study compared Doppler-guided hemorrhoid artery ligation with suture mucopexy (DGHAL-SM) and ligature-assisted pile excision (LAP) for greater than three grades of internal hemorrhoids. METHODS: Eighty patients with greater than 3 grades of internal hemorrhoids were selected (age range: 20-28 years; average age: 23 years) between January and June 2015. The patients were randomly divided into group A (DGHAL-SM) and group B (LAP); each group had 40 patients. RESULTS: With respect to the postoperative cure rate and anal skin tags, group A was inferior to group B, but the postoperative pain assessment and satisfaction were better than group B (P

Background This study was conducted to provide an overview of anesthesia services in Taiwan from 2001 to 2010. Methods A retrospective population-based analysis was performed using data from Taiwan's National Health Insurance Research Database for the period 2001 to 2010. The results were stratified by patient sex, patient age, anesthesia type, and hospital setting. Categorical data are presented as totals and percentages. Linear regression was performed to analyze the anesthesia trends. Results The annual use of anesthesia increased continually from 964,440 instances in 2001 to 1,073,160 in 2010, totaling 10,076,600 cases with a total cost of 25.4 billion USD. The overwhelming majority (83.9%) of anesthesia cases was for anesthesia in an inpatient setting; general anesthesia accounted for 73.8% of anesthesia cases, and female patients outnumbered male patients (52.4% vs. 47.6%). The average number of anesthesia cases was 44.2 per thousand of the population annually, but this percentage was much higher in elderly people (100.9 cases per thousand people annually). The annual number of anesthesia cases per thousand of the population increased from 104.4 in 2001 to 113.0 in 2010 in the oldest group (>80 years). By contrast, a considerable decline in use of anesthesia was discovered over the study period among those aged younger than 18 years. Conclusion The use of anesthesia services in Taiwan has increased over the years. The relationships of age with anesthesia volume and cost were found to follow an inverse-U-shaped pattern. Elderly people used anesthesia services more frequently. The planning of geriatric anesthesia services deserves attention, especially in continually aging societies such as Taiwan.

Light Detection and Ranging (LiDAR) is a high-price system for wide-usage automotive driving requirements. The design, implementation, and validation of a performance-complexity efficient LiDAR system are introduced in this paper. A Time-to-Digit (TDC) chip with a low-cost Data-Processing (DP) chip is utilized in this system. The proposed chips have been well validated and can be utilized as processing cores for a generic LiDAR system. The measurement accuracy is a comparison with a high-price commercial product of Time-Correlated Single-Photon-Counting (TCSPC). The values show the proposed system accuracy is respectable for the comparison by many distances from 4.8m to 44.6m, the maximum difference is 0.3%.

In this work, we successfully fabricated AlGaN/GaN HEMT on 8-inch GaN-on-Si wafer utilizing CMOS BEOL compatible process, and demonstrate an AlGaN/GaN HEMT with L g = 250nm reaching f t /f max = 50/44 GHz. By semi-automatic RF measurements mapping in complete 8-inch wafer area, results exhibit average f t = 48GHz with NU = 7.6% and average f max = 42GHz with NU = 5%, revealing the outstanding uniformity of 8-inch standard CMOS manufacturing tools.

The median overall survival (OS) of some head and neck malignancies, such as head and neck squamous cell carcinoma (HNSCC), with metastatic lesions was only 12 months. Whether aggressive pulmonary metastasectomy (PM) improves survival is controversial. Patients with primary head and neck malignancy undergoing PM were enrolled. Clinical outcomes were compared among different histological types. Whole-exome sequencing was used for matched pulmonary metastatic samples. The genes where genetic variants have been identified were sent for analysis by DAVID, IPA, and STRING. Forty-nine patients with primary head and neck malignancies were enrolled. Two-year postmetastasectomy survival (PMS) rates of adenoid cystic carcinoma, thyroid carcinoma, nasopharyngeal carcinoma, and HNSCC were 100%, 88.2%, 71.4%, and 59.2%, respectively (P = 0.024). In HNSCC, the time to distant metastasis was an independent predictive factor of the efficacy of PM. Several pathways, such as branched-chain amino acid (BCAA) consumption, were significantly associated with the progression of HNSCC [P

Objectives Cognitive impairment is common in patients with chronic kidney disease (CKD), possibly leading to poor outcomes. However, the correlation between brain structural abnormalities and cognitive impairment remains unclear. The aim of this study was to investigate the impairment of specific cognitive domains and their association with brain structural abnormalities. Methods Patients with CKD of at least stage 3 who were not on hemodialysis were enrolled. All participants underwent comprehensive neuropsychological testing in five cognitive domains. Ventricular atrophy, sulcal atrophy, medial temporal atrophy, and white matter changes were assessed using brain magnetic resonance imaging according to standard protocols. Results Eighty-seven patients and 50 controls were enrolled. Patients with CKD exhibited decreased cognitive function relative to controls. Compared with patients with stage 3 CKD, those with advanced stage (stages 4 or 5) had poorer cognitive performance, more pronounced white matter hyperintensity (WMH) and more severe ventricular atrophy. Among CKD patients, executive function (β = -.23, P = .043) and attention (β = -.29, P = .004) were associated with WMH in controlled analyses. However, no cognitive impairment was associated with ventricular atrophy. Conclusion Patients with CKD exhibited cognitive impairment and brain structural abnormalities including WMH and general brain atrophy. Impairment of attention and executive dysfunction were associated with WMH.

It is important that exopolysaccharides (EPS) of lactic acid bacteria (LAB) with antioxidant activities are produced economically, as it can confer beneficial effects on human health. A model of production possibility curve (PPC) was conducted to the optimal productivity of EPS for the purpose of economic production. The results revealed that the optimal productivity of EPS was approached to the set by NB (90%) and MRS (55%) broth from PPC with equation of PPC(Y) = 100–0.0335*EXP(0.08*X). The EPS productivity and yield of strain LaP with optimal production set (OPS) were, respectively, 291.0 ± 2.6 mg and 13.5 ± 0.7%, and the cost of OPS can be saved by about 31.6%, while that for strain BaP were 280.7 ± 2.5 mg and 13.0 ± 0.7%, respectively, and with 31.6% saved as well. Besides, the EPS produced from PPC mode has appropriate antioxidant ability with 34.6 ± 0.7% (LaP) and 37.6 ± 0.9 (%) (BaP) of DPPH radical scavenging activity under the economic cost. The strategy of controlling the medium composition not only could improve the productivity of EPS, but also enhance the antioxidant effects of EPS. Both LaP and BaP with antioxidant potential may be useful as supplements in the health‐promoting food industry.

Objective Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia. Methods In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up. Results In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values. Conclusion This study confirmed that HRV-BF is a useful psychosocial intervention for improving autonomic balance, baroreflex, and symptoms of depression and insomnia in MDD patients.

Aim To investigate the association between specific dental therapy for periodontal disease and the risk of ischaemic stroke. Materials and methods We conducted a population-based cohort study that used data from the Taiwan National Health Insurance Research Database 2005 for the period of 2000-2013. Our observations focused on patients with the diagnoses of gingivitis or periodontitis with and without specific treatment and subsequent incidence of ischaemic stroke. Dental care services include dental scaling, intensive treatment (subgingival curettage and root planing) and tooth extraction. Multivariate Cox regression analysis was used to estimate the hazard ratios and corresponding 95% confidence intervals (95% CI). Results Compared with those in the gingivitis cohort, patients with periodontitis have a higher risk of ischaemic stroke and a lower survival rate of stroke over the 10-year follow-up period. After integrative dental care, both dental scaling and intensive treatment, the risk was reduced, especially in patients with periodontitis, while patients with periodontal disease may have an increased risk of stroke after tooth extraction therapy. Conclusions Our study showed that periodontitis is a risk factor for ischaemic stroke. Both dental scaling and intensive treatment for periodontal disease are associated with a lower risk of further ischaemic stroke events.

Background and objective Fatty liver disease (FLD) is a common clinical complication; it is associated with high morbidity and mortality. However, an early prediction of FLD patients provides an opportunity to make an appropriate strategy for prevention, early diagnosis and treatment. We aimed to develop a machine learning model to predict FLD that could assist physicians in classifying high-risk patients and make a novel diagnosis, prevent and manage FLD. Methods We included all patients who had an initial fatty liver screening at the New Taipei City Hospital between 1st and 31st December 2009. Classification models such as random forest (RF), Naive Bayes (NB), artificial neural networks (ANN), and logistic regression (LR) were developed to predict FLD. The area under the receiver operating characteristic curve (ROC) was used to evaluate performances among the four models. Results A total of 577 patients were included in this study; of those 377 patients had fatty liver. The area under the receiver operating characteristic (AUROC) of RF, NB, ANN, and LR with 10 fold-cross validation was 0.925, 0.888, 0.895, and 0.854 respectively. Additionally, The accuracy of RF, NB, ANN, and LR 87.48, 82.65, 81.85, and 76.96%. Conclusion In this study, we developed and compared the four classification models to predict fatty liver disease accurately. However, the random forest model showed higher performance than other classification models. Implementation of a random forest model in the clinical setting could help physicians to stratify fatty liver patients for primary prevention, surveillance, early treatment, and management.

The carotid intimal–medial thickness (CIMT) is a strong predictor of future cardiovascular events. We assessed the mean CIMT and evaluated associated factors in head and neck cancer (HNC) patients. Between January 2016 and March 2018, 70 volunteers underwent automatic ultrasound measurement of the common carotid artery CIMT. A mean CIMT ≥ 1.0 mm was regarded as an elevated risk for cardiovascular disease (CVD). We aimed to investigate the risk factors for an increased mean CIMT. We recruited 20 HNC survivors and 50 noncancer control individuals. Multiple linear regression analysis showed that old age (β = 0.006, 95% confidence interval, CI 0.004–0.008), increased weight (β = 0.003, 95% CI 0.001–0.005), hypertension (β = 0.10, 95% CI 0.03–0.17), and prior irradiation (β = 0.13, 95% CI 0.08–0.19) were positively correlated with the mean CIMT. From logistic regression analysis, it was shown that patients who underwent radiotherapy (OR 13.5, 95% CI 1.48–122.8) and who had higher bodyweight (OR 1.09, 95% CI 1.01–1.18) had a significantly higher risk of developing CVD. Measurement of the mean CIMT using ultrasound could be useful for assessing CVD risk in HNC survivors after neck irradiation.

AIM The aim of this study was to assess the stability over time of periodontal intrabony defects treated with minimally invasive non-surgical therapy (MINST) and supportive periodontal therapy (SPT). METHODS Clinical and radiographic analysis was carried out in 21 intrabony defects treated with MINST in 14 consecutive patients included in a prospective study and reassessed after 5 years of SPT. Baseline, 1- and 5-year radiographs were analysed, and bone levels were compared by multilevel linear regression adjusted by latent variable method. RESULTS None of the 21 teeth with intrabony defects was lost at 5 years. Average probing pocket depth, clinical attachment level and radiographic intrabony vertical defect depth reductions were 3.6, 3.5 and 2.6 mm, respectively, 5 years after treatment (p

Taiwan’s brain drain has been the main concern due to China’s strong economic gravity, and the situation might have worsened over the past decade. Based on Yeh (2019), we explore the determinants for Taiwan’s youth overseas employment using the questionnaire administered in 2015 for residents between 20 and 45 years old. An empirical model is derived to investigate the push and pull factors directing Taiwan’s youth to go abroad. The empirics do not show clear evidence to support Taiwan’s brain drain by 2016. In contrast, personal considerations, such as broadening international vision and encountering career bottlenecks are more important influences for Taiwan’s youth to be employed in China.

Simple Summary The serine protease kallikrein-related peptidase 4 (KLK4) has been reported to potentially play a role in the progression of prostate cancer and other cancer types. However, most of these reports have been limited to in vitro studies. In vivo cancer models offer greater complexity to mimic the characteristics of cancer growth and metastasis in humans. In this study, we used in vivo models of prostate cancer and demonstrated that KLK4 can strongly inhibit the growth of primary prostate tumors as well as bone metastases. To our knowledge, this is the first report of an anti-tumor effect of KLK4 in prostate cancer in vivo. Abstract Recent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have been primarily in vitro studies, with limited in vivo studies performed to date. Herein, we employed an orthotopic inoculation xenograft model to mimic the growth of primary tumors, and an intracardiac injection to induce metastatic dissemination to determine the in vivo tumorigenic effects of KLK4 overexpressed in PC3 prostate cancer cells. Notably, we found that these KLK4-expressing cells gave rise to smaller localized tumors and decreased metastases than the parent PC-3 cells. To our knowledge, this is the first report of an anti-tumorigenic effect of KLK4, particularly in prostate cancer. These findings also provide a cautionary tale of the need for in vivo analyses to substantiate in vitro experimental data.

This work presents a method for obtaining a color-converted red light source through a combination of a blue GaN light-emitting diode and a red fluorescent color conversion film of a perovskite CsPbI3/TOPO composite. High-quality CsPbI3 quantum dots (QDs) were prepared using the hot-injection method. The colloidal QD solutions were mixed with different ratios of trioctylphosphine oxide (TOPO) to form nanowires. The color conversion films prepared by the mixed ultraviolet resin and colloidal solutions were coated on blue LEDs. The optical and electrical properties of the devices were measured and analyzed at an injection current of 50 mA; it was observed that the strongest red light intensity was 93.1 cd/m2 and the external quantum efficiency was 5.7% at a wavelength of approximately 708 nm when CsPbI3/TOPO was 1:0.35.

Laser-induced periodic surface structures (LIPSS) is the sub-wavelength periodic nanostructure, which is generally generated by the femtosecond laser. There are two kinds of LIPSS, low spatial frequency LIPSS (LSFL) and high spatial LIPSS (HSFL), and the period size is close and less than half of the laser wavelength, respectively. Fabrication of two-dimensional (2D) LSFL and HSFL on a titanium surface with a linear-polarized femtosecond green laser beam (wavelength 515 nm) and cross-scanning strategies is demonstrated in this study. Four types of LIPSS structures are obtained by controlling the laser fluence, irradiated pulses, and cross-scanning strategies: 1D-LSFL perpendicular to laser polarization with a period of 300&ndash, 360 nm, 1D-HSFL parallel to laser polarization with a period of 55&ndash, 75 nm, 2D-LSFL dot-like structures with a period ~200 nm, and 2D-HSFL net-like structures with a period of 50&ndash, 100 nm.

Aim The policy enforcing visiting restriction during the COVID-19 pandemic may cause feelings of social isolation among residents in long-term care facilities. This study aimed to explore family members' concerns for their relatives during the lockdown period, assess their level of acceptance of the visiting restriction policy and determine the associated factors. Methods From the 156 family members interviewed, demographic data, satisfaction with overall care quality, worry and concerns for their relatives, acceptance of the visiting restriction and arrangement for the residents if cluster infections occur in the facility were recorded. Results Among the members interviewed, 83 (53.2%) were men; mean age of members was 56.3 ± 9.8; most were offspring of residents in the facility (n = 121, 77.6%), most visited the residents at least once a week (n = 113, 72.4%) before the lockdown. The most common concerns of the family members for their relatives were psychological stress (38.5%), followed by nursing care (26.9%) and daily activity (21.1%). Nearly 84.6% of those interviewed accepted the visiting restriction policy, and a higher satisfaction rating independently associated with acceptance of the visiting restriction policy (odds ratio 2.15). Conclusions During the lockdown period, staff members should provide more psychological information about residents to their family members. Higher satisfaction rating was found to be independent of the acceptance of the visiting restriction policy. Therefore, good quality of care of the facility wins the trust of family members, and this might mitigate the tension between the family members and staff during a major crisis. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; 20: 938-942.

Quaternary AlInGaN/GaN high-electron-mobility transistors (HEMTs) grown on high-resistivity silicon wafer were fabricated, with T-gate of 0.14 μm footprint. The HEMTs devices exhibit I ds,sat = 908 mA/mm and g m = 451 mS/mm. In small-signal operation, cut-off frequency F T /F MAX = 100/97 GHz are achieved, which gives a high value of (F T *L g ) = 13.9 GHz*μm among the reported GaN-on-Si devices. In large signal operation, power density of 1.7 W/mm and PAE = 33% were achieved at 10GHz, and 1.1 W/mm and PAE = 20% at 28 GHz.

Objective: To determine the perceptions of US community-based hematologists/oncologists regarding approved CAR-T therapies in relapsed/refractory large B-cell lymphoma and barriers to their adoption in practice. Materials & methods: In February and November 2019, US physicians with diverse geographic representation submitted responses via a web-based survey prior to or via an audience response system at the live meetings. Results: In February and November, 46 and 29% of physicians indicated that they had not referred any patients for CAR-T therapy, respectively. Cumbersome logistics, high cost and toxicity were defined as major barriers to prescribing CAR-T therapy. Conclusions: These findings highlight a need to improve processes, and address costs, to ensure timely access to this potentially curative therapy for relapsed/refractory large B-cell lymphoma patients.

Importance: Before introducing strategy training into a cross-cultural (Chinese) context, it is necessary to evaluate its feasibility. Objective: To examine the feasibility of applying strategy training to improve participation outcomes of rehabilitation patients in Taiwan and evaluate the potential intervention effects. Design: A single-group, repeated-measures study. Setting: Rehabilitation outpatient settings. Participants: A convenience sample of adults (N = 20) with a primary diagnosis of acquired brain injury (ABI) and with cognitive impairment received the intervention and were assessed before and after it. Intervention: The participation-focused strategy training intervention, a modified version of the strategy training intervention, was provided to participants in 1–2 sessions weekly for a total of 10–20 intervention sessions. Outcomes and Measures: Feasibility indicators, Participation Measure–3 Domains, 4 Dimensions (PM–3D4D), and Canadian Occupational Performance Measure (COPM). Results: Eighteen participants completed 100% of the scheduled intervention sessions. Participants had very good engagement in the intervention sessions with sufficient comprehension. Participants reported moderate to high satisfaction. Positive score changes were observed for the PM–3D4D (d = 0.46–1.25) and COPM scales (d = 1.82 and 2.12). Conclusions and Relevance: This study demonstrated the feasibility of delivering participation-focused strategy training in Taiwan to people with cognitive impairment after ABI. The preliminary evidence also showed that participants who received the strategy training intervention had positive changes in participation outcomes and in performance of their self-identified goals. On the basis of this study’s findings, a larger clinical trial is warranted to evaluate the efficacy of the strategy training intervention. What This Article Adds: Participation-focused strategy training is feasible and acceptable for Taiwanese community-dwelling adults with cognitive impairment after ABI. However, because strategy training is quite different from traditional rehabilitation delivered in Taiwan, additional instructions and discussion among the therapist, client, and caregiver may be needed before the intervention is provided.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) pump flow is crucial for maintaining tissue and organ perfusion in patients with cardiogenic shock. Determining the optimal VA-ECMO pump flow rate to maintain adequate tissue perfusion remains a clinical challenge. Poor microcirculation is associated with higher mortality in patients using VA-ECMO. Change in VA-ECMO pump flow is expected to result in a coherent change in microcirculatory blood flow, but this has not been investigated. This study investigated the effect of altering VA-ECMO pump flow rate on sublingual microcirculation. Methods: Sublingual microcirculation images were recorded using an incident dark-field hand held vital microscope at two time points, within 24 h (T1) and at 24-48 h (T2) after VA-ECMO placement. Microcirculation was measured before and 5 minutes after the changes in VA-ECMO pump flow rate at each time point. Events of changing VA-ECMO pump flow rate at T1 and T2 were divided into four groups according to changes in perfused vessel density (PVD): Group A, increased pump flow rate and increased or sustained PVD; Group B, increased pump flow rate and decreased PVD; Group C, decreased pump flow rate and increased or sustained PVD; and Group D, decreased pump flow rate and decreased PVD. The microcirculatory parameters, clinical parameters, and prognosis of each subgroup were recorded. Clinical parameters on 14-day and 28-day survivors and non-survivors were also compared. Results: A total of 25 patients were enrolled, and 38 events with good-quality images at T1 and T2 were categorized. Opposing response of microcirculation was observed in 43.5% of events when VA-ECMO pump flow rate was increased. Microcirculation was decreased in 33.4% of events when VA-ECMO pump flow rate was reduced. No predictive values in microcirculatory or macrocirculatory parameters before changing VA-ECMO pump flow rate were identified. Conclusions: Changes in VA-ECMO pump flow rate may have opposing effects on sublingual microcirculatory functional capillary density. We suggest that tandem measurements of microcirculation before and after altering the VA-ECMO pump flow may help to ensure optimal tissue perfusion.

Botulinum toxin A (BTX-A) is a powerful neurotoxin with long-lasting activity that blocks muscle contractions. In addition to effects on neuromuscular junctions, BTX-A also plays a role in sensory feedback loops, suggesting the potentiality for pain relief. Although the only approved indications for BTX-A in the bladder are neurogenic detrusor overactivity and refractory overactive bladder, BTX-A injections to treat bladder pain refractory to conventional therapies are also recommended. The mechanism of BTX-A activity in bladder pain is complex, with several hypotheses proposed in recent studies. Here we comprehensively reviewed properties of BTX-A in peripheral afferent and efferent nerves, the inhibition of nociceptive neurotransmitter release, the reduction of stretch-related visceral pain, and its anti-inflammatory effects on the bladder urothelium. Studies have also revealed possible effects of BTX-A in the human brain. However, further basic and clinical studies are warranted to provide solid evidence-based support in using BTX-A to treat bladder pain.

The major challenge of FRAM scaling is to maintain high polarization density on the vertical sidewall of 3D ferroelectric capacitors. We reported a CMOS-compatible HfZrO x FRAM technology that shows a wake-up free character, 1010/109 endurance cycles, extrapolated 10-year retention at 105°C/85°C, and initial P r = 25/18 μC/cm2 for 2D/3D FRAM, respectively. The strain effect at atomic interfaces is considered by the density functional theory (DFT) simulation. Two simple yet effective methods, stress engineering and optimized interface orientation, are proposed to facilitate preferential transition from tetragonal to orthorhombic phase. The test chip of 2T2C 3D FRAM demonstrates a fast sensing speed of 17 MHz at V DD of 4V.

Background: In recent decades, issues related to end-of-life care and advance care planning (ACP) have attracted popular attention. Advance care planning has been broadly discussed as one of the potential solutions to protect a patient’s rights, autonomy, and dignity at the end of life. To better understand publishing on this topic, we conducted this study to demonstrate the worldwide research productivity, trends, and citations of ACP in the past 3 decades by bibliometric analysis. Methods: Articles published on ACP were retrieved from the Web of Science Core Collection database, and the subject terms included “advance directive,” or “advance care planning.” Results: Overall, 2126 publications on ACP were retrieved until January 22, 2019. North America, Western Europe, and Australia were the most productive regions. The top 15 countries published 95.9% of the total number of articles. The United States accounted for approximately three-fifths (61.0%) of all publications. When adjusted for population size, Australia had the highest number of articles per million persons (6.64), followed by the Netherlands (6.14) and Belgium (4.61). The most productive authors were Sudore (n = 37), Deliens (n = 29), and Green (n = 24). Conclusions: The current study revealed that research in terms of publications on ACP has rapidly increased over the past 3 decades. Developed countries, especially the United States, were more concerned with the ACP research field than developing countries were.

Objective To assess the efficacy and safety of different endoscopic surgical treatments for benign prostatic hyperplasia. Design Systematic review and network meta-analysis of randomised controlled trials. Data sources A comprehensive search of PubMed, Embase, and Cochrane databases from inception to 31 March 2019. Study selection Randomised controlled trials comparing vapourisation, resection, and enucleation of the prostate using monopolar, bipolar, or various laser systems (holmium, thulium, potassium titanyl phosphate, or diode) as surgical treatments for benign prostatic hyperplasia. The primary outcomes were the maximal flow rate (Qmax) and international prostate symptoms score (IPSS) at 12 months after surgical treatment. Secondary outcomes were Qmax and IPSS values at 6, 24, and 36 months after surgical treatment; perioperative parameters; and surgical complications. Data extraction and synthesis Two independent reviewers extracted the study data and performed quality assessments using the Cochrane Risk of Bias Tool. The effect sizes were summarised using weighted mean differences for continuous outcomes and odds ratios for binary outcomes. Frequentist approach to the network meta-analysis was used to estimate comparative effects and safety. Ranking probabilities of each treatment were also calculated. Results 109 trials with a total of 13 676 participants were identified. Nine surgical treatments were evaluated. Enucleation achieved better Qmax and IPSS values than resection and vapourisation methods at six and 12 months after surgical treatment, and the difference maintained up to 24 and 36 months after surgical treatment. For Qmax at 12 months after surgical treatment, the best three methods compared with monopolar transurethral resection of the prostate (TURP) were bipolar enucleation (mean difference 2.42 mL/s (95% confidence interval 1.11 to 3.73)), diode laser enucleation (1.86 (−0.17 to 3.88)), and holmium laser enucleation (1.07 (0.07 to 2.08)). The worst performing method was diode laser vapourisation (−1.90 (−5.07 to 1.27)). The results of IPSS at 12 months after treatment were similar to Qmax at 12 months after treatment. The best three methods, versus monopolar TURP, were diode laser enucleation (mean difference −1.00 (−2.41 to 0.40)), bipolar enucleation (0.87 (−1.80 to 0.07)), and holmium laser enucleation (−0.84 (−1.51 to 0.58)). The worst performing method was diode laser vapourisation (1.30 (−1.16 to 3.76)). Eight new methods were better at controlling bleeding than monopolar TURP, resulting in a shorter catheterisation duration, reduced postoperative haemoglobin declination, fewer clot retention events, and lower blood transfusion rate. However, short term transient urinary incontinence might still be a concern for enucleation methods, compared with resection methods (odds ratio 1.92, 1.39 to 2.65). No substantial inconsistency between direct and indirect evidence was detected in primary or secondary outcomes. Conclusion Eight new endoscopic surgical methods for benign prostatic hyperplasia appeared to be superior in safety compared with monopolar TURP. Among these new treatments, enucleation methods showed better Qmax and IPSS values than vapourisation and resection methods. Study registration CRD42018099583.