Short-term and long-term outcomes after robotic radical surgery for rectal gastrointestinal stromal tumor.

BACKGROUND: The optimal approach for ensuring both complete resection and preservation of anal function in rectal gastrointestinal stromal tumor (GIST) remains unknown. The aim of this study was to clarify short-term and long-term outcomes after robotic radical surgery for rectal GIST. METHODS: A total of 13 patients who underwent robotic radical surgery for rectal GIST between December 2011 and April 2022 were included. All robotic procedures were performed using a systematic approach. A supplemental video of robotic radical surgery for rectal GIST is attached. The short-term outcome was the incidence of postoperative complications during the first 30 days after surgery. Surgical outcomes were retrieved from a prospective database. Long-term outcomes, including overall survival and recurrence-free survival, were determined in all patients. RESULTS: Median distance from the tumor to the anal verge was 4.0 cm. Surgical margins were negative in all patients. Two patients underwent neoadjuvant imatinib therapy. All patients underwent sphincter-preserving surgery. None underwent conversion to open or laparoscopic surgery. The incidence of postoperative Clavien-Dindo grade II and grade ≥ III complications was 7.7% and 0%, respectively. The median postoperative hospital stay was 7 days. Twelve patients (92.3%) underwent stoma closure within 5 months of the initial surgery. Median follow-up time was 76 months. The 5-year overall survival and recurrence-free survival rates were both 100%. None of the patients had recurrence. CONCLUSION: Short-term and long-term outcomes after radical robotic surgery for rectal GIST were favorable. Robotic surgery might be a useful surgical approach for rectal GIST.

Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).

Building a model for predicting metabolic syndrome using artificial intelligence based on an investigation of whole-genome sequencing.

BACKGROUND: The circadian system is responsible for regulating various physiological activities and behaviors and has been gaining recognition. The circadian rhythm is adjusted in a 24-h cycle and has transcriptional-translational feedback loops. When the circadian rhythm is interrupted, affecting the expression of circadian genes, the phenotypes of diseases could amplify. For example, the importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed as mutations in genes coding for core components of the clock result in diseases. This study will investigate the association between circadian genes and metabolic syndromes in a Taiwanese population. METHODS: We performed analysis using whole-genome sequencing, read vcf files and set target circadian genes to determine if there were variants on target genes. In this study, we have investigated genetic contribution of circadian-related diseases using population-based next generation whole genome sequencing. We also used significant SNPs to create a metabolic syndrome prediction model. Logistic regression, random forest, adaboost, and neural network were used to predict metabolic syndrome. In addition, we used random forest model variables importance matrix to select 40 more significant SNPs, which were subsequently incorporated to create new prediction models and to compare with previous models. The data was then utilized for training set and testing set using five-fold cross validation. Each model was evaluated with the following criteria: area under the receiver operating characteristics curve (AUC), precision, F1 score, and average precision (the area under the precision recall curve). RESULTS: After searching significant variants, we used Chi-Square tests to find some variants. We found 186 significant SNPs, and four predicting models which used 186 SNPs (logistic regression, random forest, adaboost and neural network), AUC were 0.68, 0.8, 0.82, 0.81 respectively. The F1 scores were 0.412, 0.078, 0.295, 0.552, respectively. The other three models which used the 40 SNPs (logistic regression, adaboost and neural network), AUC were 0.82, 0.81, 0.81 respectively. The F1 scores were 0.584, 0.395, 0.574, respectively. CONCLUSIONS: Circadian gene defect may also contribute to metabolic syndrome. Our study found several related genes and building a simple model to predict metabolic syndrome.

Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD.

OBJECTIVE: During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. METHODS: Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. RESULTS: Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1-276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6-97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013-0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199-0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. INTERPRETATION: This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088-1098.

Modified distributed Bragg reflector for protecting organic light-emitting diode displays against ultraviolet light.

Sunlight/UV (ultraviolet)-induced degradation is still a critical issue for outdoor applications of organic light-emitting diode (OLED) displays. Therefore, effective UV-blocking structures that can prevent OLED displays from sunlight/UV degradation and still keep the OLED panels' display performance is necessary. In this report, modified distributed Bragg reflector (DBR) structures having UV-absorbing dielectric materials and adjusted layer/pair thicknesses were developed to realize effective UV blocking properties (nearly 0% transmittance below 400 nm), constantly high transmittance like glass in the visible range (∼92%) required for display applications, and sharp transition in transmission between the UV and the visible ranges. Furthermore, under the rigorous IEC 60068-2-5 solar test condition, it was verified that the developed modified, UV-blocking DBR can effectively enhance the OLED panel's resistance against UV/solar-induced degradation, effectively reducing voltage shifts of OLED devices after repeated solar test cycles.

A rapid molecular diagnostic method for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder which has been considered as the second common cause of infant death, with an estimated prevalence of 1 in 10,000 live births. The disorder is caused by survival motor neuron 1 gene (SMN1) deficiency leading to limb weakness, difficult swallowing and abnormal breathing. Here, a fast and accurate method for SMA detection has been developed. Genomic DNA sample collected from whole blood, amniotic fluid, or dried blood spots can be analysed by using the Clarity™ Digital PCR (dPCR) System for determining the copy numbers of SMN1 and SMN2 genes. Two hundred and fourteen clinical samples determined by qPCR-based method were enrolled and used to establish the cut-off ranges for unaffected individual, SMA carrier and SMA patient categories. After setting the cut-off range for each group, 12 samples were analyzed by both dPCR-based method and MLPA (multiplex ligation-dependent probe amplification), the current testing golden standard for SMA, and 100% concordant results between the two testing methods were performed. CSB SMA Detection Kit combined with dPCR platform provides a robust and precise approach to distinguish unaffected individuals, SMA carrier and SMA patients. This rapid molecular diagnostic method can be adapted to pre-pregnancy eugenics inspection, prenatal testing as well as newborns screening and help physicians or genetic counselors to improve population SMA incidence.

Nanoparticle Assembling Dynamics Induced by Pulsed Optical Force.

Femtosecond (fs) laser trapping dynamics is summarized for silica, hydrophobically modified silica, and polystyrene nanoparticles (NPs) in aqueous solution, highlighting their distinct optical trapping dynamics under CW laser. Mutually repulsive silica nanoparticles are tightly confined under fs laser compared to CW laser trapping and, upon increasing laser power, they are ejected from the focus as an assembly. Hydrophobically modified silica and polystyrene (PS) NPs are sequentially ejected just like a stream or ablated, giving bubbles. The ejection and bubbling take place with the direction perpendicular to laser polarization and its direction is randomly switched from one to the other. These characteristic features are interpreted from the viewpoint of single assembly formation of NPs at an asymmetric position in the optical potential. Temporal change in optical forces map is prepared for a single PS NP by calculating scattering, gradient, and temporal forces. The relative contribution of the forces changes with the volume increase of the assembly and, when the pushing force along the trapping pulse propagation overcome the gradient in the focal plane, the assembly undergoes the ejection. Further fs multiphoton absorption is induced for the larger assembly leading to bubble generation. The assembling, ejection, and bubbling dynamics of NPs are characteristic features of pulsed optical force and are considered as a new platform for developing new material fabrication method.

Synthesis of benzoxazole-based vorinostat analogs and their antiproliferative activity.

Hydroxamic acid derivatives constitute an interesting novel class of antitumor agents. Three of them, including vorinostat, are approved drugs for the treatment of malignancies, while several others are currently under clinical trials. In this work, we present new vorinostat analogs containing the benzoxazole ring as the cap group and various linkers. The benzoxazole-based analogs were synthesized starting either from 2-aminobenzoxazole, through conventional coupling, or from benzoxazole, through a metal-free oxidative amination. All the synthesized compounds were evaluated for their antiproliferative activity on three diverse human cancer cell lines (A549, Caco-2 and SF268), in comparison to vorinostat. Compound 12 (GK601), carrying a benzoxazole ring replacement for the phenyl ring of vorinostat, was the most potent inhibitor of the growth of three cell lines (IC50 1.2-2.1 µΜ), similar in potency to vorinostat. Compound 12 also inhibited human HDAC1, HDAC2 and HDAC6 like vorinostat. This new analog also showed antiproliferative activity against two colon cancer cell lines genetically resembling pseudomyxoma peritonei (PMP), namely HCT116 GNAS R201C/+ and LS174T (IC50 0.6 and 1.4 µΜ, respectively) with potency comparable to vorinostat (IC50 1.1 and 2.1 µΜ, respectively).

Establishment of a fluorescent PCR melting curve method for detecting asthma susceptibility using gene SNP typing.

Objective: To develop a detection method for single nucleotide polymorphisms (SNPs) of bronchial asthma (BA) susceptibility genes (IL-13, IL-33, and GSDMA) based on fluorescence PCR melting curves.Methods: Peripheral blood samples from 33 patients with BA were collected. DNA was extracted, and positive plasmids were constructed. Probes and primers for fluorescence polymerase chain reaction (PCR) were designed according to IL-13, IL-33, and GSDMA sequences, and the SNPs were separately detected by gene sequencing and fluorescence PCR melting curve.Results: The system was successfully divided into 3 SNPs, including IL-13, IL-33, and GSDMA, and a comparison of sequencing methods showed that the results were completely consistent. The lowest detection limit was 1 ng/reaction, the sensitivity and specificity were 100%, and this method had high repeatability (CV = 2.8%).Conclusion: The fluorescence PCR melting curve method is suitable for the rapid and accurate classification of SNPs. The method is economical, simple, and efficient, and is suitable for the screening of the susceptible gene SNPs in a large-scale population of patients with BA.

Effects of the COVID-19 Pandemic on Obsessive-Compulsive Symptoms Among University Students: Prospective Cohort Survey Study.

BACKGROUND: The COVID-19 pandemic is associated with common mental health problems. However, evidence for the association between fear of COVID-19 and obsessive-compulsive disorder (OCD) is limited. OBJECTIVE: This study aimed to examine if fear of negative events affects Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores in the context of a COVID-19-fear-invoking environment. METHODS: All participants were medical university students and voluntarily completed three surveys via smartphone or computer. Survey 1 was conducted on February 8, 2020, following a 2-week-long quarantine period without classes; survey 2 was conducted on March 25, 2020, when participants had been taking online courses for 2 weeks; and survey 3 was conducted on April 28, 2020, when no new cases had been reported for 2 weeks. The surveys comprised the Y-BOCS and the Zung Self-Rating Anxiety Scale (SAS); additional items included questions on demographics (age, gender, only child vs siblings, enrollment year, major), knowledge of COVID-19, and level of fear pertaining to COVID-19. RESULTS: In survey 1, 11.3% of participants (1519/13,478) scored ≥16 on the Y-BOCS (defined as possible OCD). In surveys 2 and 3, 3.6% (305/8162) and 3.5% (305/8511) of participants had scores indicative of possible OCD, respectively. The Y-BOCS score, anxiety level, quarantine level, and intensity of fear were significantly lower at surveys 2 and 3 than at survey 1 (P<.001 for all). Compared to those with a lower Y-BOCS score (<16), participants with possible OCD expressed greater intensity of fear and had higher SAS standard scores (P<.001). The regression linear analysis indicated that intensity of fear was positively correlated to the rate of possible OCD and the average total scores for the Y-BOCS in each survey (P<.001 for all). Multiple regressions showed that those with a higher intensity of fear, a higher anxiety level, of male gender, with sibling(s), and majoring in a nonmedicine discipline had a greater chance of having a higher Y-BOCS score in all surveys. These results were redemonstrated in the 5827 participants who completed both surveys 1 and 2 and in the 4006 participants who completed all three surveys. Furthermore, in matched participants, the Y-BOCS score was negatively correlated to changes in intensity of fear (r=0.74 for survey 2, P<.001; r=0.63 for survey 3, P=.006). CONCLUSIONS: Our findings indicate that fear of COVID-19 was associated with a greater Y-BOCS score, suggesting that an environment (COVID-19 pandemic) × psychology (fear and/or anxiety) interaction might be involved in OCD and that a fear of negative events might play a role in the etiology of OCD.

Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy.

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1-2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

[Effect of density and directional cultivation on yield, quality and benefit of Nuomi yam].

A split-plot experiment was conducted to study the optimum planting density of Nuomi yam in directional groove shallow cultivation. Nuomi yam was the main local cultivar of Dioscorea. The study of this paper may help to give valuable instructions of local production. Three different planting densities and shallow groove diameter were designed in the experiment. The results showed that the fresh weight of aerial part per plant, yield and planting benefit of Nuomi yam tuber were the highest when the planting density was 12 000 plants/hm~2 and the diameter of shallow growth groove was 11.0 cm, while they were the lowest when the planting density was 22 500 plants/hm~2 and the diameter of shallow growth groove was 7.5 cm. Along with the increase of planting density, the fresh weight of aerial part, tuber, fresh yield, benefit and commercial tuber rate of Nuomi yam also decreased. The commercial tuber rate of Nuomi yam of 11.0 cm diameter in shallow growing pot was the highest, while it was the lowest with no shallow growing pot. On the contrary, the content of amylopectin and mucin was the highest when there was no shallow groove, and was the lowest when the diameter of shallow groove was 7.5 cm, although there was no significant difference between the two treatments. Therefore, Nuomi yam with the directional cultivation combination of planting density of 12 000 plants/hm~2 and shallow groove diameter of 11.0 cm showed high yield, good appearance quality, high planting benefit and no obvious adverse effect on internal quality.

Health impact assessment of PM2.5 from a planned coal-fired power plant in Taiwan.

PURPOSE: To investigate the impact of a planned coal-fired power plant (CFPPT) in Shenao on air quality and health at subnational levels in Taiwan. METHODS: We applied the Gaussian trajectory transfer-coefficient (GTx) model to estimate annual average PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) increments in 19 Taiwanese cities and counties caused by CFPPT operation. A population health risk assessment was performed by incorporating evidence of the health effects of PM2.5 provided by prospective studies and estimating long-term PM2.5 exposure. Additionally, we considered ischemic heart disease, stroke, lung cancer, and chronic obstruct pulmonary disease as the primary outcomes. The population-attributable fraction was used to estimate the county-level mortality burden attributable to CFPPT-generated PM2.5 in 2025. RESULTS: The estimated annual PM2.5 increments ranged from 0.004 µg/m3 (Taitung County) to 0.28 µg/m3 (Hsinchu County) due to the Shenao CFPPT. The total and premature deaths attributable to PM2.5 from Shenao CFPPT operation in Taiwan during 2025-2040 would be 576 (95% confidence interval [CI]: 537-619) and 145 (95% CI: 136-155), respectively. Notably, we estimated 198 (95% CI: 169-234) deaths and 58 (95% CI: 51-66) premature deaths, respectively, in New Taipei City, which accounted for over a quarter of the total deaths. Overall, the mortality rate attributable to the Shenao CFPPT in Taiwan was 6 per 10,000. CONCLUSION: A scientific approach should be adopted for assessing the impacts of CFPPT operation on population health, which can serve as a valuable policymaking reference for the government.

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anticitrullinated peptide antibodies. The orchestra of the inflammatory process among various immune cells, cytokines, chemokines, proteases, matrix metalloproteinases (MMPs), and reactive oxidative stress play critical immunopathologic roles in the inflammatory cascade of the joint environment, leading to clinical impairment and RA. With the growing understanding of the immunopathogenic mechanisms, increasingly novel marked and potential biologic agents have merged for the treatment of RA in recent years. In this review, we focus on the current understanding of pathogenic mechanisms, highlight novel biologic disease-modifying antirheumatic drugs (DMRADs), targeted synthetic DMRADs, and immune-modulating agents, and identify the applicable immune-mediated therapeutic strategies of the near future. In conclusion, new therapeutic approaches are emerging through a better understanding of the immunopathophysiology of RA, which is improving disease outcomes better than ever.

A Potent Antagonist of Protease-Activated Receptor 2 That Inhibits Multiple Signaling Functions in Human Cancer Cells.

Protease-activated receptor 2 (PAR2) is a cell surface protein linked to G-protein dependent and independent intracellular signaling pathways that produce a wide range of physiological responses, including those related to metabolism, inflammation, pain, and cancer. Certain proteases, peptides, and nonpeptides are known to potently activate PAR2. However, no effective potent PAR2 antagonists have been reported yet despite their anticipated therapeutic potential. This study investigates antagonism of key PAR2-dependent signaling properties and functions by the imidazopyridazine compound I-191 (4-(8-(tert-butyl)-6-(4-fluorophenyl)imidazo[1,2-b]pyridazine-2-carbonyl)-3,3-dimethylpiperazin-2-one) in cancer cells. At nanomolar concentrations, I-191 inhibited PAR2 binding of and activation by structurally distinct PAR2 agonists (trypsin, peptide, nonpeptide) in a concentration-dependent manner in cells of the human colon adenocarcinoma grade II cell line (HT29). I-191 potently attenuated multiple PAR2-mediated intracellular signaling pathways leading to Ca2+ release, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, Ras homologue gene family, member A (RhoA) activation, and inhibition of forskolin-induced cAMP accumulation. The mechanism of action of I-191 was investigated using binding and calcium mobilization studies in HT29 cells where I-191 was shown to be noncompetitive and a negative allosteric modulator of the agonist 2f-LIGRL-NH2 The compound alone did not activate these PAR2-mediated pathways, even at high micromolar concentrations, indicating no bias in these signaling properties. I-191 also potently inhibited PAR2-mediated downstream functional responses, including expression and secretion of inflammatory cytokines and cell apoptosis and migration, in human colon adenocarcinoma grade II cell line (HT29) and human breast adenocarcinoma cells (MDA-MB-231). These findings indicate that I-191 is a potent PAR2 antagonist that inhibits multiple PAR2-induced signaling pathways and functional responses. I-191 may be a valuable tool for characterizing PAR2 functions in cancer and in other cellular, physiological, and disease settings.

Europium-Labeled Synthetic C3a Protein as a Novel Fluorescent Probe for Human Complement C3a Receptor.

Measuring ligand affinity for a G protein-coupled receptor is often a crucial step in drug discovery. It has been traditionally determined by binding putative new ligands in competition with native ligand labeled with a radioisotope of finite lifetime. Competing instead with a lanthanide-based fluorescent ligand is more attractive due to greater longevity, stability, and safety. Here, we have chemically synthesized the 77 residue human C3a protein and conjugated its N-terminus to europium diethylenetriaminepentaacetate to produce a novel fluorescent protein (Eu-DTPA-hC3a). Time-resolved fluorescence analysis has demonstrated that Eu-DTPA-hC3a binds selectively to its cognate G protein-coupled receptor C3aR with full agonist activity and similar potency and selectivity as native C3a in inducing calcium mobilization and phosphorylation of extracellular signal-regulated kinases in HEK293 cells that stably expressed C3aR. Time-resolved fluorescence analysis for saturation and competitive binding gave a dissociation constant (Kd) of 8.7 ± 1.4 nM for Eu-DTPA-hC3a and binding affinities for hC3a (pKi of 8.6 ± 0.2 and Ki of 2.5 nM) and C3aR ligands TR16 (pKi of 6.8 ± 0.1 and Ki of 138 nM), BR103 (pKi of 6.7 ± 0.1 and Ki of 185 nM), BR111 (pKi of 6.3 ± 0.2 and Ki of 544 nM) and SB290157 (pKi of 6.3 ± 0.1 and Ki of 517 nM) via displacement of Eu-DTPA-hC3a from hC3aR. The macromolecular conjugate Eu-DTPA-hC3a is a novel nonradioactive probe suitable for studying ligand-C3aR interactions with potential value in accelerating drug development for human C3aR in physiology and disease.

Adult atopic dermatitis and exposure to air pollutants-a nationwide population-based study.

BACKGROUND: There is a trend toward an increased worldwide prevalence of allergic diseases. It is speculated that industrialization with resultant air pollution plays a role. However, there are sparse epidemiologic data on the relation between air pollution and atopic dermatitis (AD) in adults. OBJECTIVE: To investigate the relation between exposure to air pollutants and adult AD in a cross-sectional study based on data from the National Health Insurance Research Database in Taiwan. METHODS: We identified 1,023 adult patients with AD and 4,092 age- and sex-matched controls without allergic diseases in 2011. Using data from 71 Environmental Protection Agency monitoring stations across Taiwan, levels of exposure to air pollutants were determined by the location of a subject's place of residence. Multivariate logistic regression analysis, adjusted for age, sex, levels of urbanization, and family income, was performed. RESULTS: We found an association between particulate matter <2.5 µm in diameter or the Pollutant Standards Index (the highest sub-index of the concentrations of 5 main air pollutants after transformation) and the development of adult AD. The adjusted odds ratios were 1.05 (95% confidence interval 1.02-1.08) and 1.02 (95% confidence interval 1.01-1.03), respectively. CONCLUSION: These results demonstrated that air pollution, represented by particulate matter <2.5 µm in diameter or the Pollutant Standards Index, was modestly associated with the development of AD in adults.

Intermittent Pringle maneuver versus continuous hemihepatic vascular inflow occlusion using extra-glissonian approach in laparoscopic liver resection.

BACKGROUND: Despite accumulated experience and advancing techniques for laparoscopic hepatectomy, bleeding remains the major concern during parenchymal transection. The vascular inflow control technique is still important to decrease intraoperative blood loss. The objective of this study was to compare intermittent Pringle with continuous hemihepatic vascular inflow occlusion using extra-glissonian approach in laparoscopic liver resection. METHODS: Between January 2011 and January 2015, a total of 79 consecutive patients with tumors locating either in the right or in the left hemiliver were included into this retrospective study (45 in the Pringle group vs. 34 in the half-Pringle group). Preoperative clinical characteristics, intraoperative details, postoperative complications and outcomes of patients were compared. RESULTS: The two groups were well matched according to clinical characteristics, tumor features, types of liver resection and histopathology (P > 0.05). The mean operative time (247.5 ± 61.3 vs. 221.4 ± 48.7 min, P = 0.0446), ischemic duration (62.8 ± 28.3 vs. 44.1 ± 20.5 min, P = 0.0017) and overall declamping time (21.2 ± 8.2 vs. 0.9 ± 1.9 min, P < 0.05) were significantly longer in the Pringle group than in the half-Pringle group. The mean amount of intraoperative blood loss (568.2 ± 325.1 vs. 420.7 ± 307.2 mL, P = 0.0444) and transfusion (266.1 ± 123.4 vs. 203.2 ± 144.6 mL, P = 0.0406) were significantly greater in the Pringle group. The overall operative morbidity rate was significantly higher in the Pringle group (40 vs. 17.6%, P = 0.0324). The Pringle group was associated with significantly higher alanine aminotransferase and aspartate transaminase levels on postoperative day (POD) 7 and lower albumin levels on PODs 1 and 3 (P < 0.05). The C-reactive protein levels were significantly higher in the Pringle group than in the half-Pringle group on POD 1 (37.5 ± 21.4 vs. 28.2 ± 19.0 mg/L, P = 0.0484), POD 3 (114.0 ± 53.4 vs. 90.6 ± 47.9 mg/L, P = 0.0474) and POD 7 (54.9 ± 29.8 vs. 40.1 ± 26.4 mg/L, P = 0.0245). CONCLUSION: Continuous hemihepatic vascular inflow occlusion using extra-glissonian approach offers the advantages of less operative time and blood loss, less injury and better recovery in laparoscopic liver resection.

Evaluation and characterization of a high-resolution melting analysis kit for rapid carrier-screening test of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by the homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA. Several assays have been described for molecular diagnosis or carrier screening of SMA. A newly developed tool based on a high-resolution melting analysis (HRMA) that enables high-throughput screening without sophisticated protocols but low costs reveals itself to be powerful. We evaluate the performance of an HRMA-based kit for a carrier-screening test of SMA that was designed to detect the substitution of a single nucleotide in SMN1 exon 7. Carriers were identified in 453 participants by quantifying the SMN1 gene and compared with denaturing high-performance liquid chromatography (DHPLC) assay. An HRMA-based kit had a higher sensitivity (100%) for carrier testing than the DHPLC assay (93%), with the added advantage that some homozygous sequence alterations could be identified. The HRMA kit is a new, fast, and highly reliable quantitative test for the SMA molecular carrier test.