Monodansylpentane as a Blue-Fluorescent Lipid-Droplet Marker for Multi-Color Live-Cell Imaging

Lipid droplets (LDs) are dynamic cellular organelles responsible for the storage of neutral lipids, and are associated with a multitude of metabolic syndromes. Here we report monodansylpentane (MDH) as a high contrast blue-fluorescent marker for LDs. The unique spectral properties make MDH easily combinable with other green and red fluorescent reporters for multicolor fluorescence imaging. MDH staining does not apparently affect LD trafficking, and the dye is extraordinarily photo-stable. Taken together MDH represents a reliable tool to use for the investigation of dynamic LD regulation within living cells using fluorescence microscopy

Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors:population based cohort study

OBJECTIVE: To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia. DESIGN: Population based cohort study. SETTING: UK Clinical Practice Research Datalink (CPRD; 2003-14) and Taiwanese National Health Insurance Research Database (NHIRD; 2002-12). PARTICIPANTS: Men in the CPRD who received dutasteride (n=8231), finasteride (n=30 774), or tamsulosin (n=16 270) were evaluated. Propensity score matching (2:1; dutasteride to finasteride or tamsulosin) produced cohorts of 2090, 3445, and 4018, respectively. In the NHIRD, initial numbers were 1251 (dutasteride), 4194 (finasteride), and 86 263 (tamsulosin), reducing to 1251, 2445, and 2502, respectively, after propensity score matching. MAIN OUTCOMES MEASURE: Incident type 2 diabetes using a Cox proportional hazard model. RESULTS: In the CPRD, 2081 new onset type 2 diabetes events (368 dutasteride, 1207 finasteride, and 506 tamsulosin) were recorded during a mean follow-up time of 5.2 years (SD 3.1 years). The event rate per 10 000 person years was 76.2 (95% confidence interval 68.4 to 84.0) for dutasteride, 76.6 (72.3 to 80.9) for finasteride, and 60.3 (55.1 to 65.5) for tamsulosin. There was a modest increased risk of type 2 diabetes for dutasteride (adjusted hazard ratio 1.32, 95% confidence interval 1.08 to 1.61) and finasteride (1.26, 1.10 to 1.45) compared with tamsulosin. Results for the NHIRD were consistent with the findings for the CPRD (adjusted hazard ratio 1.34, 95% confidence interval 1.17 to 1.54 for dutasteride, and 1.49, 1.38 to 1.61 for finasteride compared with tamsulosin). Propensity score matched analyses showed similar results. CONCLUSIONS: The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes

Identification of the genetic determinants of Salmonella enterica serotype Typhimurium that may regulate the expression of the type 1 fimbriae in response to solid agar and static broth culture conditions

<p>Abstract</p> <p>Background</p> <p>Type 1 fimbriae are the most commonly found fimbrial appendages on the outer membrane of <it>Salmonella enterica </it>serotype Typhimurium. Previous investigations indicate that static broth culture favours <it>S</it>. Typhimurium to produce type 1 fimbriae, while non-fimbriate bacteria are obtained by growth on solid agar media. The phenotypic expression of type 1 fimbriae in <it>S</it>. Typhimurium is the result of the interaction and cooperation of several genes in the <it>fim </it>gene cluster. Other gene products that may also participate in the regulation of type 1 fimbrial expression remain uncharacterized.</p> <p>Results</p> <p>In the present study, transposon insertion mutagenesis was performed on <it>S</it>. Typhimurium to generate a library to screen for those mutants that would exhibit different type 1 fimbrial phenotypes than the parental strain. Eight-two mutants were obtained from 7,239 clones screened using the yeast agglutination test. Forty-four mutants produced type 1 fimbriae on both solid agar and static broth media, while none of the other 38 mutants formed type 1 fimbriae in either culture condition. The flanking sequences of the transposons from 54 mutants were cloned and sequenced. These mutants can be classified according to the functions or putative functions of the open reading frames disrupted by the transposon. Our current results indicate that the genetic determinants such as those involved in the fimbrial biogenesis and regulation, global regulators, transporter proteins, prophage-derived proteins, and enzymes of different functions, to name a few, may play a role in the regulation of type 1 fimbrial expression in response to solid agar and static broth culture conditions. A complementation test revealed that transforming a recombinant plasmid possessing the coding sequence of a NAD(P)H-flavin reductase gene <it>ubiB </it>restored an <it>ubiB </it>mutant to exhibit the type 1 fimbrial phenotype as its parental strain.</p> <p>Conclusion</p> <p>Genetic determinants other than the <it>fim </it>genes may involve in the regulation of type 1 fimbrial expression in <it>S</it>. Typhimurium. How each gene product may influence type 1 fimbrial expression is an interesting research topic which warrants further investigation.</p

Prenatal Diagnosis of Pulmonary Sequestration by Ultrasound and Magnetic Resonance Imaging

A 36-year-old multigravida, G2P1, underwent routine ultrasound scan at 22+1 weeks of gestation, which revealed a single normally growing fetus with left intrathoracic mass and left displacement of the cardiac apex. The left intrathoracic wedge-shaped hyperechogenic mass, measuring 32 × 25 mm in size, was situated at the lower portion of the left lung. A combination of color and power Doppler ultrasound allowed visualization of a vessel arising from the descending aorta, which supplied the mass. The diagnosis of extralobar pulmonary sequestration was made. Magnetic resonance imaging (MRI) was also performed and revealed a well-defined mass with homogeneous high-signal intensity when compared with normal lung tissue in the left upper lung field, which was compatible with pulmonary sequestration. The pulmonary mass was followed up by color and power Doppler every 2 weeks. The peak velocity of 11.85 cm/sec and the diameter of the feeding artery of 1.19 mm gradually decreased and disappeared 8 weeks later. The intrathoracic mass disappeared 10 weeks later at 32+1 gestational weeks. Repeat MRI also revealed spontaneous regression of the mass in favor of resorption of sequestration. The fetus was delivered at 38+1 gestational weeks. A male newborn weighing 2,520 g was spontaneously delivered with an Apgar score of 8 at 1 minute and 9 at 5 minutes. In our patient, it is suggested that progressive decreases in the peak velocity of the feeding vessel heralded the spontaneous regression of pulmonary sequestration not associated with hydrops/hydrothorax

Mediating role of resilience in the relationships of physical activity and mindful self-awareness with peace of mind among college students

Abstract Peace of mind (PoM) is an index of mental health in Asian culture and emphasizes low arousal, happiness, harmony, and an internal state of peacefulness. While previous studies have found that mindful self-awareness can contribute to PoM, regular physical activity (PA) is also an important factor contributing to one’s PoM due to its function in promoting one's resilience. The study aims to investigate a hypothetical model that assumes PA is associated with resilience while controlling for mindful self-awareness, contributing to PoM. The PoM scale, Connor-Davidson Resilience Scale, Chinese translation of Mindful Attention Awareness Scale, and PA self-report questionnaire were used. A path analysis was applied to test the association between these variables and the mediating role of resilience. A total of 436 students from a university in Taiwan were recruited; the mean age was 20.87, with 46.3% female and 73.6% engaging in over 150 min/week of moderate PA. Gender and age negatively correlated with PA. After controlling for age and gender, there was no direct effect of physical activity on PoM; both mindful self-awareness and PA predict resilience, which in turn predicts PoM, suggesting that both cognitive (i.e., mindful self-awareness) and PA are important to cultivate resilience and thus PoM

AMiBA Wideband Analog Correlator

A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.Comment: 28 pages, 23 figures, ApJ in press

Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and Hb

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke

Background: Atrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting. Methods: This nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of “ischemic stroke recurrence, ICH, or death.” Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: A total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70–0.99), death (aHR, 0.65; 95% CI, 0.58–0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63–0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62–1.50) was not significantly different between the two cohorts. Conclusion: OAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis

Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag