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Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Objective To assess the safety and efficacy of a simplified initialization for the Tandem tslim X2 Control-IQ hybrid closed-loop system, using parameters based on total daily insulin ("MyTDI") in adolescents with type 1 diabetes under usual activity and during periods of increased exercise. Research Design and Methods Adolescents with type 1 diabetes 12-18 years of age used Control-IQ for 5 days at home using their usual parameters. Upon arrival at a 60-h ski camp, participants were randomized to either continue Control-IQ using their home settings or to reinitialize Control-IQ with MyTDI parameters. Control-IQ use continued for 5 days following camp. The effect of MyTDI on continuous glucose monitoring outcomes were analyzed using repeated measures analysis of variance (ANOVA) baseline, camp, and at home. Results Twenty participants were enrolled and completed the study; two participants were excluded from the analysis due to absence from ski camp (1) and illness (1). Time in range was similar between both groups at home and camp. A tendency to higher time 40% tended to show greater time in the euglycemic range improvements between baseline and home than users with ratios less then 40% (+16.3% vs. -9.0%, P = 0.012). All participants maintained an average of 95% time in closed loop (84.1%-100%). Conclusions MyTDI is a safe, effective, and easy way to determine insulin parameters for use in the Control-IQ artificial pancreas. Future modifications to account for the influence of carbohydrate intake on MyTDI calculations might further improve time in range.I was honored to be asked by the Editorial Committee of the Annual Review of Genomics and Genetics to write an autobiographical account of my life in science and in genetics in particular. The field has moved from mapping Mendelian disorders 40 years ago to the delivery of effective therapies for some monogenic disorders today. My 40-year journey from diagnosis to therapy for Duchenne muscular dystrophy has depended on collaborations among basic scientists, clinicians, medical charities, genetic counselors, biotech companies, and affected families. find more The future of human genetics looks even more exciting, with techniques such as single-cell sequencing and somatic cell CRISPR editing opening up opportunities for precision medicine and accelerating progress. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 21 is August 31, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Background and aim Role of 5-aminosalicylic acid (5-ASA), statin and aspirin in reducing cancer risks in inflammatory bowel disease (IBD) remains controversial. We aimed to examine chemo-preventive effects of these drugs in all cancers in IBD in population-based setting.Methods IBD patients diagnosed between 2000 and 2016 were identified from the Hong Kong IBD Registry and followed from IBD diagnosis until first cancer occurrence. Primary outcome was cancer development ≥6 months after IBD diagnosis. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated with Cox proportional hazards model. Additional effects of statin and aspirin on chemoprevention were also assessed.Results Amongst 2103 IBD patients (857 Crohn's disease, 1246 ulcerative colitis; mean age 40.0 ± 15.6; 60.3% male) with 16,856 person-years follow-up, 48 patients (2.3%) developed cancer. The 5-r, 10-r and 15-year (95% CI) cumulative incidence of cancer were 1% (0.6 - 1.5%), 2.8 (2.0 - 3.9%) and 4.8 (3.4 - 6.5%), respectivelyand showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD.The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6-1.5%), 2.8 (2.0-3.9%) and 4.8 (3.4-6.5%), respectively.Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.Purpose The methylene tetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and the methionine synthase reductase (MTRR) A66G polymorphisms are the three most common folate metabolism-related loci in the Chinese population. They are associated with numerous birth defects or congenital diseases. To facilitate screening and genetic counseling, we established a method for the simultaneous detection of these three polymorphisms using the Luminex liquid suspension chip and multiple asymmetric polymerase chain reactions (PCRs). Materials and Methods The three polymorphisms were amplified by multiplex PCR with biotinylated primers, followed by hybridization with six probe-linked magnetic microspheres. The mean fluorescent intensity value in each microsphere was detected by Luminex Magpix for polymorphism detection in 150 samples and confirmed by sequencing. Results The consistency between the Luminex liquid suspension chip method and sequencing was 100%. Among the 150 randomized samples, the minor allele frequency (MAF) of MTHFR C677T was 0.41, which was the most common variant allele, followed by MTRR A66G (MAF = 0.24), and finally MTHFR A1298C (MAF = 0.19). Conclusion The Luminex liquid suspension chip method can replace sequencing to analyze the MTHFR C677T, MTRR A1298C, and MTRR A66G loci simultaneously as a rapid, convenient, accurate, and stable method for large-scale testing.Background Cervical cancer (CC) is one of the most common cancers among women worldwide. Circular RNAs (circRNAs) are recently identified as important gene regulators with critical roles in cancer biology. In this study, we explored the effects of circ_0000388 on the malignant phenotypes of CC cells and its mechanism. Materials and Methods Circ_0000388 expression and miR-337-3p expression in CC tissue samples were measured using quantitative real time polymerase chain reaction. CCK-8 was adopted to assess the effect of circ_0000388 on CC cell line proliferation. link2 TUNEL assay was employed to probe the effect of circ_0000388 on apoptosis. Wound healing assay and transwell assay were conducted to detect the effect of circ_0000388 on migration and invasion. Further, interaction among circ_0000388, miR-337-3p, and TCF12 (transcription factor 12) was determined by bioinformatics analysis, RT-PCR, western blot, RNA immunoprecipitation assay, and luciferase reporter assay. Results Circ_0000388 expression in CC clinical samples was upregulated and this was correlated with unfavorable pathological indexes. Circ_0000388 remarkably enhanced the proliferation and metastasis of CC cells. Circ_0000388 overexpression dramatically impeded miR-337-3p expression and it was identified as a sponge of miR-337-3p. Furthermore, circ_00003888 also enhanced the TCF12 expression, while the effect could be reversed by co-transfection with miR-377-3p. Conclusions Circ_0000388 was a novel oncogenic circRNA in CC, and promoted cancer progression via regulating miR-337-3p and TCF12, and could be potentially used as a diagnostic biomarker and therapy target.BACKGROUND The Segond fracture is an avulsion of the anterolateral tibia that can be found in patients with an anterior cruciate ligament (ACL) tear. It is currently unclear if the Segond fracture needs treatment or if it heals spontaneously and if it is associated with an increased risk of failure after ACL reconstruction. PURPOSE To identify the incidence and spontaneous healing rate of Segond fractures in a consecutive cohort of patients undergoing ACL reconstruction and to examine the predictive value of the Segond fracture on the risk of undergoing revision surgery. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS A retrospective review of a cohort undergoing isolated ACL reconstruction between 2002 and 2016 was performed. Radiographs from the time of injury and preoperative radiographs were evaluated for Segond fractures and healed Segond fractures. Descriptive data were extracted from an internal quality database. Statistical analyses were performed to investigate risk of revision surgery and t spontaneous healing rate from initial radiographs to preoperative imaging was only 36%, the presence of Segond fractures did not represent a higher risk of undergoing revision surgery.Swine disease models are essential for mimicry of human metabolic and vascular pathophysiology, thereby enabling high-fidelity translation to human medicine. The worldwide epidemic of obesity, metabolic disease, and diabetes has prompted the focus on these diseases in this review. We highlight the remarkable similarity between Ossabaw miniature swine and humans with metabolic syndrome and atherosclerosis. Although the evidence is strongest for swine models of coronary artery disease, findings are generally applicable to any vascular bed. We discuss the major strengths and weaknesses of swine models. The development of vascular imaging is an example of optimal vascular engineering in swine. Although challenges regarding infrastructure and training of engineers in the use of swine models exist, opportunities are ripe for gene editing, studies of molecular mechanisms, and use of swine in coronary artery imaging and testing of devices that can move quickly to human clinical studies. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 22 is June 4, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Perfluoroalkyl chemicals induce male reproductive toxicity. Current evidence showed the effects of the chemical exposure on the deterioration of testicular functions, and reduction in epididymal sperm counts. Previous studies showed that PFOA and PFOS displayed a high correlation with each other in seminal plasma levels, but induced different effects on semen variables. In this study, we focused on the comparative toxicity analysis of PFOA and PFOS, using a rat primary Sertoli cell model. Our transcriptomic data showed that PFOA and PFOS treatments (40 μM) perturbed global gene expression. While PFOS induced higher toxicity in affecting cytoskeleton signaling, Sertoli cell-cell junction, and inflammation, underlined by Ingenuity pathway analysis. Immunocytochemical staining revealed that PFOS treatment (40 and 80 μM) induced truncated actin filament and disorganized bundled configuration in the cell cytoplasm. link3 Moreover, disorganized distribution of N-cadherin (N-cad) and β-catenin (β-cat), and defragmentation of ZO-1 at the Sertoli cell-cell interface was evident. At 80 μM of PFOS, cytoplasmic distribution of N-cad, β-cat, and ZO-1 were observed. We then examined whether resveratrol, a polyphenol antioxidant, was able to protect the cells from PFOS toxicity. The pretreatment of Sertoli cells with 10 μM resveratrol prevented the formation of truncated actin filament and dis-localization of β-cat. Western blot analysis showed that Res pretreatment increased the levels of basal ES proteins (N-cad and β-cat), tight junction proteins (ZO-1 and occludin), and gap junction protein, versus control.Exploring formation of diatomic radicals in femtosecond plasmas is important to establish the most dominant kinetic pathways following ionization and dissociation of small molecules. In this work, cyano radical formation has been studied from bromoform, acetonitrile and methanol in nitrogen and argon plasmas created with a focused femtosecond laser beam operating at 100 kHz repetition rate and 1030 nm wavelength with 43 fs pulse length and 250 J pulse energy. Time-resolved Fourier transform fluorescence spectroscopy was applied in the ultraviolet-visible (UV-Vis) spectral range for the characterization of the rotational and vibrational temperatures of the CN(B) radicals via fitting the experimental data. The high repetition rate of the laser allows efficient coupling with the step scan Fourier transform spectroscopy method. Coulomb explosion at the very high intensity (~1016 W/cm2) resulted in the formation of nascent atoms, ions and electrons. The condensation reactions of carbon and reactive nitrogen species resulted in the formation of CN(B2Σ+) radicals and C2(d3g) dicarbon molecules/radicals.

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