Coordination of pancreatic islet rhythmic activity by delayed negative feedback.

Secretion of insulin from the pancreas is pulsatile, driven by intrinsic oscillations within individual islets of Langerhans. The secretions are coordinated among the many islets distributed throughout the pancreas producing a synchronized rhythm in vivo that is essential for maintaining normal glucose levels. One hypothesized mechanism for the coordination of islet activity is negative feedback, whereby sequestration of glucose in response to elevated insulin leads to a reduction in the blood glucose level that is sensed by the islet population. This global signal of glucose then coordinates the individual islets. In this study, we tested how this coordination mechanism is affected by time delays in the negative feedback, using a microfluidic system to monitor Ca2+ levels in a small population of islets and implementing glucose control through a negative feedback system. We found that islet synchronization occurs even with time delays in the feedback of up to 7 min. We also found that a second, slower closed-loop oscillation period is produced during delayed feedback in which islet oscillations are clustered into episodes. The period of this second oscillatory mode increases with the time delay and appears to be a second stable behavior that coexists with the faster synchronized oscillation. The general conclusion is that islet coordination through negative feedback is a viable means of islet coordination that is robust to delays in the timing of the feedback, and could complement other potential coordination mechanisms such as entrainment by pancreatic ganglia.NEW & NOTEWORTHY Insulin secretion from islets of Langerhans is rhythmic, and these rhythms are coordinated to produce oscillatory plasma insulin levels. Using a combination of microfluidics and computational modeling, we demonstrate that coordination can occur through negative feedback of the type provided by the liver, even if that feedback is delayed by several minutes. We also demonstrate that a second, slower, mode of oscillations can occur when feedback is delayed where faster oscillations are grouped into episodes.

Effect of benign prostatic hyperplasia on the development of spine, hip, and wrist fractures.

Benign prostatic hyperplasia is one of the most common diseases in the elderly male population. The urinary tract symptoms may increase the risk of falls and fractures. The results indicated that patients with benign prostatic hyperplasia could increase the risk of vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. INTRODUCTION: The relationship between benign prostatic hyperplasia and the development of fall-related fractures, especially vertebral compression fractures, has been seldom mentioned in the literature. This study aimed to evaluate the risk of developing vertebral compression fracture, hip fracture, and wrist fracture in patients with benign prostatic hyperplasia. METHODS: This study obtained claims data retrospectively from the National Health Insurance Research Database of Taiwan and identified 48,114 patients who were diagnosed as having benign prostatic hyperplasia. Subjects of the control cohort were individually matched at a ratio of 4:1 with those in the benign prostatic hyperplasia cohort according to age and the index day. Comorbidities were classified as those existing before the index day and included a previous fracture history, osteoporosis, myocardial infarction, congestive heart failure, diabetes mellitus, hypertension, cerebrovascular accident, etc. The end of the follow-up period of the analyses was the day when the patient developed new vertebral compression fractures, hip fractures, or wrist fractures, terminated enrollment from the National Health Insurance, or died or until the end of 2012. The study used the Cox proportion hazard model to determine the hazard ratio for developing new hip fractures. RESULTS: Patients with benign prostatic hyperplasia were significantly more likely than those in the control cohort to develop new vertebral compression fractures in the thoracic spine (0.43% vs. 0.40%, adjusted hazard ratio 3.03, confidence interval 2.12-4.31) and lumbar spine (1.26% vs. 1.23%, adjusted hazard ratio 4.12, confidence interval 3.39-5.01), and hip fracture (1.47% vs. 2.09%, adjusted hazard ratio 1.22, confidence interval 1.10-1.36), but does not increase the risk of wrist fracture (0.61% vs. 0.67%, adjusted hazard ratio 1.07, confidence interval 0.85-1.34). CONCLUSIONS: Patients with benign prostatic hyperplasia exhibited an increased risk of developing vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. However, more research is needed to confirm this trend in the clinical setting.

Bulk Fermi Surfaces of the Dirac Type-II Semimetallic Candidates MAl_{3} (Where M=V, Nb, and Ta).

We report a de Haas-van Alphen (dHvA) effect study on the Dirac type-II semimetallic candidates MAl_{3} (where, M=V, Nb and Ta). The angular dependence of their Fermi surface (FS) cross-sectional areas reveals a remarkably good agreement with our first-principles calculations. Therefore, dHvA supports the existence of tilted Dirac cones with Dirac type-II nodes located at 100, 230 and 250 meV above the Fermi level ϵ_{F} for VAl_{3}, NbAl_{3} and TaAl_{3} respectively, in agreement with the prediction of broken Lorentz invariance in these compounds. However, for all three compounds we find that the cyclotron orbits on their FSs, including an orbit nearly enclosing the Dirac type-II node, yield trivial Berry phases. We explain this via an analysis of the Berry phase where the position of this orbit, relative to the Dirac node, is adjusted within the error implied by the small disagreement between our calculations and the experiments. We suggest that a very small amount of doping could displace ϵ_{F} to produce topologically nontrivial orbits encircling their Dirac node(s).

The Impact of the Shallow-Trench Isolation Effect on Flicker Noise of Source Follower MOSFETs in a CMOS Image Sensor.

The flicker noise of source follower transistors is the dominant noise source in image sensors. This paper reports a systematic study of the shallow trench isolation effect in transistors with different sizes under high temperature conditions that correspond to the quantity of empty defect sites. The effects of shallow trench isolation sidewall defects on flicker noise characteristics are investigated. In addition, the low-frequency noise and subthreshold swing degrade simultaneously in accordance to the device gate width scaling. Both serious subthreshold leakage and considerable noise can be attributed to the high trap density near the STI edge. Consequently, we propose a coincidental relationship between the noise level and the subthreshold characteristic; its trend is identical to the experiments and simulation results.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.

Evaluation of nasal patency by visual analogue scale/nasal obstruction symptom evaluation questionnaires and anterior active rhinomanometry after septoplasty: a retrospective one-year follow-up cohort study.

OBJECTIVE: To assess the efficacy of septoplasty and the correlation between the subjective evaluations of a visual analogue scale (VAS) and the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire and active anterior rhinomanometry of the nasal airway after septoplasty. DESIGN: A retrospective, individual cohort study. SETTING: Ear, Nose and Throat Department, Taipei City Hospital, Taipei, Taiwan. PARTICIPANTS: Fifty patients with chronic nasal obstruction were enrolled in the study. All 50 patients underwent septoplasty because of nasal septal deviation. Another 28 patients without nasal symptoms served as controls. MAIN OUTCOME MEASURES: VAS, NOSE and active anterior rhinomanometry were used to measure the sensation of nasal obstruction. All measurements were performed in both groups preoperatively and then repeated on three postoperative visits (3, 6 and 12 months). RESULTS: The mean VAS score, NOSE score and the nasal resistance in the narrow side of the nose in the study group showed reduced symptoms at 3, 6 and 12 months postoperatively compared with the respective preoperative measurements (P < 0.001, all). The VAS and NOSE scores did not significantly correlate with total nasal resistance preoperatively or postoperatively. The VAS and nasal resistance in the obstructed nasal cavity correlated significantly preoperatively (P < 0.05), but not postoperatively. CONCLUSIONS: The subjective and objective symptoms of nasal obstruction had improved 1 year after septoplasty. A significant correlation between VAS scores and nasal resistance in the narrow side of the nose was found before surgery. The subjective and objective measurements of nasal obstruction lacked significant correlation postoperatively.

Predictive factors for inadequate colon preparation before colonoscopy.

BACKGROUND: It could be helpful to ascertain which patients are at risk of poor bowel preparation prior to performing sedated colonoscopy. The aim of the present study was to identify the predictive factors for poor colon preparation prior to colonoscopy. METHODS: A prospective study was performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient characteristics, food consumed within 2 days of colonoscopy, volume of polyethylene glycol (PEG) solution, interval between completing PEG and examination, number of bowel movements, and character of the last stool were evaluated. RESULTS: Seven hundred and three patients were enrolled (mean age 50.3 ± 11.6 years, 43 % female). In univariate analysis, character of the last stool (<0.001), body weight (p = 0.007), body mass index (p = 0.047), waist circumference (p = 0.008), buttock girth (p = 0.016), meal residue score (<0.001), and interval between end of PEG and colonoscopy (p = 0.01) were related to inadequate colon preparation. In multivariate analysis, waist circumference (p < 0.001), meal residue score (p < 0.001), and characteristics of last stool (p < 0.001) were variables that predicted poor colon preparation. CONCLUSIONS: Patients who have consumed a high residue diet and/or who report that their last stool is semisolid are likely to have poor bowel preparation, and consideration could be given to rescheduling the examination.

Occurrence and distribution of Naegleria species from thermal spring environments in Taiwan.

UNLABELLED: Naegleria spp. is a free-living amoeba that can be found in the natural environment. A number of Naegleria spp. can cause fatal infections in the central nervous system in humans and animals, and the most important source of infection is through direct water contact. In this study, water samples from various thermal springs were taken from four thermal spring areas. Naegleria spp. was detected via culture confirmation and molecular taxonomic identification. Among the 60 samples obtained, Naegleria spp. was identified in 26 (43·3%) samples. The identified species included Naegleria australiensis, Naegleria gruberi, Naegleria lovaniensis and Naegleria mexicana. The presence of living Naegleria spp. was significantly associated with elevated pH value in the water sample. SIGNIFICANCE AND IMPACT OF STUDY: In this study, we examined the presence of living Naegleria spp. in thermal spring waters in south-eastern Taiwan. Naegleria spp. was isolated and culture-confirmed from thermal spring water. Naegleria fowleri was not found in all water samples, and Naegleria australiensis was the most common Naegleria genotype.

Absence of Zika virus among pregnant women in Vietnam in 2008.

BACKGROUND: Despite being first identified in 1947, Zika virus-related outbreaks were first described starting from 2007 culminating with the 2015 Latin American outbreak. Hypotheses indicate that the virus has been circulating in Asia for decades, but reports are scarce. METHODS: We performed serological analysis and screened placental samples isolated in 2008 for the presence of Zika virus from pregnant women in Ho Chi Minh City (Vietnam). RESULTS: None of the placental samples was positive for Zika virus. Four serum samples out of 176 (2.3%) specifically inhibited Zika virus, with variable degrees of cross-reactivity with other flaviviruses. While one of the four samples inhibited only Zika virus, cross-reactivity with other flaviviruses not included in the study could not be ruled out. CONCLUSION: Our results support the conclusion that the virus was not present among pregnant women in the Vietnamese largest city during the initial phases of the epidemic wave.

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury.

AIMS/HYPOTHESIS: Sympathetic nerves influence islet hormone levels in the circulation. Insights into islet sympathetic innervation and its remodelling in diabetes may impact future therapeutics. However, standard immunohistochemistry and microtome-based microscopy cannot provide an integral view of the islet neurovascular complex. We prepared transparent islet specimens to investigate the spatial relationship between sympathetic nerves, blood vessels and islet cells in normal, streptozotocin-injected and non-obese diabetic mouse models. METHODS: Cardiac perfusion of fluorescent lectin was used to label pancreatic blood vessels. Tyrosine hydroxylase and nuclear staining were used to reveal islet sympathetic innervation and microstructure. Optical clearing (i.e. use of immersion solution to reduce scattering) was applied to enable 3-dimensional confocal microscopy of islets to visualise the sympathetic neurovascular complex in space. RESULTS: Unlike previously reported morphology, we observed perfusive intra-islet, perivascular sympathetic innervation, in addition to peri-islet contacts of sympathetic nerves with alpha cells and sympathetic fibres encircling the adjacent arterioles. The intra-islet axons became markedly prominent in streptozotocin-injected mice (2 weeks after injection). In non-obese diabetic mice, lymphocytic infiltration remodelled the peri-islet sympathetic axons in early insulitis. CONCLUSIONS/INTERPRETATION: We have established an imaging approach to reveal the spatial features of mouse islet sympathetic innervation. The neurovascular complex and sympathetic nerve-alpha cell contact suggest that sympathetic nerves modulate islet hormone secretion through blood vessels, in addition to acting directly on alpha cells. In islet injuries, sympathetic nerves undergo different remodelling in response to different pathophysiological cues.

Risk factors influencing the outcome of peptic ulcer bleeding in end stage renal diseases after initial endoscopic haemostasis.

Background and Aims: Patients suffering from peptic ulcer (PU) bleeding who have end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary objective is to investigate the risk factors that influence the outcomes of ESRD and chronic kidney disease (CKD) patients with PU bleeding after successful initial endoscopic haemostasis. Methods: A total of 540 patients with PU bleeding after initial endoscopic haemostasis in a tertiary hospital were investigated retrospectively. They were sorted into three groups after randomised age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group (n = 360). Main outcome measurements were rebleeding, requirement for blood transfusion and surgery, length of hospital stay and mortality. Results: The rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12% for the control group (overall p = < 0.001). Multivariate analysis showed the predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton-pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall score. All-cause mortality was related to presence of moderate degree of CKD and ESRD group, platelet count, time to endoscope, Rockall score and length of hospital stay. Conclusions: ESRD patients who suffered from PU bleeding were at risk of excessive rebleeding and mortality with frequent occurrence of delayed rebleeding. This study suggests that early endoscopy for initial haemostasis and high-dose intravenous PPI are associated with the reduction of rebleeding risk especially in patients with high Rockall scores.

Role of 2-month sputum smears in predicting culture conversion in pulmonary tuberculosis.

Sputum smears and culture conversion are frequently used to evaluate treatment response in pulmonary tuberculosis patients. Limited data are available on the evaluation of the correlation between under-treatment sputum smear results and culture conversion. This prospective study included sputum culture-proven pulmonary tuberculosis patients at six hospitals in Taiwan. At least two sets of sputum were collected at the completion of 8 weeks of TB treatment. The sensitivities and specificities of 2-month sputum smears were estimated based on culture conversion status. A total of 371 patients were enrolled for analysis. Factors associated with culture conversion included having a smear positive before treatment, presence of a cavity on radiography, rifampicin resistance and usage of the DOTS (directly observed therapy, short course) strategy. The sensitivities of 2-month sputum smears for culture conversion among all patients, initially smear-positive patients and initially smear-negative patients were 64.3, 71.4 and 38%, respectively, and the specificities were 81.6, 69.9 and 92.8%, respectively. In patients who were 2-month sputum smear-positive, the 2-month culture conversion rate was 80% if the patients were under DOTS and without cavitary lesions in radiograms. The predictive value of 2-month sputum smears in culture conversion was limited and highly influenced by clinical factors in pulmonary tuberculosis patients.

Characterizing protein activities on the lysozyme and nanodiamond complex prepared for bio applications.

Recently, nanodiamond particles have attracted increasing attention as a promising nanomaterial for its biocompatibility, easy functionalization and conjugation with biomolecules, and its superb physical/chemical properties. Nanodiamonds are mainly used as markers for cell imaging, using its fluorescence or Raman signals for detection, and as carriers for drug delivery. For the success of these applications, the biomolecule associated with the nanodiamond has to retain its functionality. In this work, the protein activities of egg white lysozyme adsorbed on nanodiamond particles of different sizes is investigated. The lysozyme nanodiamond complex is used here as a protein model for analyzing its structural conformation changes and, correspondingly, its enzymatic activity after the adsorption. Fourier-transform infrared spectroscopy (FTIR) is used for the analysis of the sensitive protein secondary structure. To access the activities of the adsorbed lysozyme, a fluorescence-based assay is used. The process of adsorption is also analyzed using UV-visible spectroscopic measurements in combination with analysis of nanodiamond properties with FTIR, Raman spectroscopy, and ζ-potential measurements. It is found that the activity of lysozyme upon adsorption depends on the nanodiamond's size and surface properties, and that the nanodiamond particles can be selected and treated, which do not alter the lysozyme functional properties. Such nanodiamonds can be considered convenient nanoparticles for various bioapplications.

Treating high-mercury-containing lamps using full-scale thermal desorption technology.

The mercury content in high-mercury-containing lamps are always between 400 mg/kg and 200,000 mg/kg. This concentration is much higher than the 260 mg/kg lower boundary recommended for the thermal desorption process suggested by the US Resource Conservation and Recovery Act. According to a Taiwan EPA survey, about 4,833,000 cold cathode fluorescent lamps (CCFLs), 486,000 ultraviolet lamps and 25,000 super high pressure mercury lamps (SHPs) have been disposed of in the industrial waste treatment system, producing 80, 92 and 9 kg-mercury/year through domestic treatment, offshore treatment and air emissions, respectively. To deal with this problem we set up a full-scale thermal desorption process to treat and recover the mercury from SHPs, fluorescent tube tailpipes, fluorescent tubes containing mercury-fluorescent powder, and CCFLs containing mercury-fluorescent powder and monitor the use of different pre-heating temperatures and desorption times. The experimental results reveal that the average thermal desorption efficiency of SHPs and fluorescent tube tailpipe were both 99.95%, while the average thermal desorption efficiencies of fluorescent tubes containing mercury-fluorescent powder were between 97% and 99%. In addition, a thermal desorption efficiency of only 69.37-93.39% was obtained after treating the CCFLs containing mercury-fluorescent powder. These differences in thermal desorption efficiency might be due to the complexity of the mercury compounds contained in the lamps. In general, the thermal desorption efficiency of lamps containing mercury-complex compounds increased with higher temperatures.

Chopart amputation with tibiotalocalcaneal arthrodesis and free flap reconstruction for severe foot crush injury.

AIMS: This study reports the outcomes of a technique of soft-tissue coverage and Chopart amputation for severe crush injuries of the forefoot. PATIENTS AND METHODS: Between January 2012 to December 2016, 12 patients (nine male; three female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent treatment in our institute. All patients were followed-up for at least one year. Their medical records, imaging, visual analogue scale score, walking ability, complications, and functional outcomes one year postoperatively based on the American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health Survey (SF-36) scores were reviewed. RESULTS: The mean length of follow-up was 18.6 months (13 to 28). Two patients had a local infection, flap necrosis was seen in one patient, and one patient experienced a skin graft wound healing delay. Of the 12 patients, one had persistent infection and eventually required below-knee amputation, but pain-free walking was achieved in all the other patients. The mean one-year postoperative AOFAS and SF-36 scores were 75.6 (68 to 80) and 82 (74 to 88), respectively. CONCLUSION: Although our sample size was small, we believe that this treatment method may be a valuable alternative for treating severe foot crush injuries. Cite this article: Bone Joint J 2018;100-B:1359-63.

Cost Analysis and Determinants of Living Donor Liver Transplantation in Taiwan.

BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.

Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia.

Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML.