Association between maternal pre-delivery body mass index and offspring overweight/obesity at 1 and 2 years of age among residents of a suburb in Taiwan

Background Overweight and obesity among children can cause metabolic syndrome in adulthood and are a significant public health issue. Some studies suggest that maternal pre-pregnancy body mass index (BMI) and excessive gestational weight gain during pregnancy are associated with overweight and obesity in offspring. However, it is difficult to collect information on accurate pre-pregnancy BMI and pregnancy weight gain for women living in areas where medical resources are scarce. Maternal pre-delivery BMI might be predictive of the risk of overweight and obesity among offspring of pregnant mothers living in suburban areas. Methods We retrospectively collected data on term neonates with appropriate weights for their gestational age born between April 2013 and October 2015. We excluded neonates with major congenital anomalies or diseases and incomplete data. Mothers with systemic diseases or drug abuse were also excluded. Offspring body weights and heights at 1- and 2-years-old were recorded. Maternal pre-delivery BMI was divided into following groups: <25, 25–29.9, and ≧30 kg/m2. Results We included 261 mother-child pairs in this study. The BMIs of the offspring differed significantly among the three maternal pre-delivery BMI groups at the age of 2 years (15.18 ± 1.04, 15.83 ± 1.28, and 16.29 ± 1.61 kg/m2, p < 0.001, respectively). After adjusting for potential cofounders possibly affecting weight using multivariate linear regression, the children’s BMIs (adjusted 95% CI: 0.71 [0.31–1.11]; p = 0.001) and BMI percentiles (adjusted 95% CI 15.80 [7.32–24.28]; p < 0.001) at the age of 2 years were significantly higher in those born to mothers with pre-delivery BMIs of 25–29.9 kg/m2 compared to mothers with pre-delivery BMIs <25 kg/m2. Maternal pre-delivery BMI ≧30 kg/m2 was significantly associated with increased BMIs (adjusted 95% CI: 1.17 [0.72–1.63]; p < 0.001) and BMI percentiles (adjusted 95% CI: 23.48 [13.87–33.09]; p < 0.001) in their children. A maternal pre-delivery BMI of 27.16 kg/m2 was the optimal cut-off for predicting offspring overweight/obesity at the age of 2 years. Discussion Our results indicate that the maternal pre-delivery BMI was significantly associated with offspring BMI and weight gain at the age of 2 years. A maternal pre-delivery BMI of 27.16 kg/m2 might be a useful predictor for estimating the risk of overweight or obesity in offspring at the age of 2 years

Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa

Background Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. Case presentation Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain–optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. Conclusions We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP

Thermal Conductivity of Carbon Nanotubes and their Polymer Nanocomposites: A Review

Thermally conductive polymer composites offer new possibilities for replacing metal parts in several applications, including power electronics, electric motors and generators, heat exchangers, etc., thanks to the polymer advantages such as light weight, corrosion resistance and ease of processing. Current interest to improve the thermal conductivity of polymers is focused on the selective addition of nanofillers with high thermal conductivity. Unusually high thermal conductivity makes carbon nanotube (CNT) the best promising candidate material for thermally conductive composites. However, the thermal conductivities of polymer/CNT nanocomposites are relatively low compared with expectations from the intrinsic thermal conductivity of CNTs. The challenge primarily comes from the large interfacial thermal resistance between the CNT and the surrounding polymer matrix, which hinders the transfer of phonon dominating heat conduction in polymer and CNT. This article reviews the status of worldwide research in the thermal conductivity of CNTs and their polymer nanocomposites. The dependence of thermal conductivity of nanotubes on the atomic structure, the tube size, the morphology, the defect and the purification is reviewed. The roles of particle/polymer and particle/particle interfaces on the thermal conductivity of polymer/CNT nanocomposites are discussed in detail, as well as the relationship between the thermal conductivity and the micro- and nano-structure of the composite

Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online)

BACKGROUND: The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. RESULTS: Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO , to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. CONCLUSION: This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment

Genetic and phenotypic profiling of single living circulating tumour cells from patients with microfluidics

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non–small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Examination of the interactions between amyloid proteins and cell membrane

目前發現，人體內至少有20種不同的蛋白質，與致病性的澱粉沈澱(amyloid deposits)的纖維組成(fibrillar components)有關。而因蛋白質發生大小或形狀上的變化，產生聚集，進一步造成類澱粉症(amyloidosis)，也就是蛋白質構象病(protein conformational disease)；其中，類澱粉β蛋白質(β-amyloid, Aβ)為導致阿滋海默症(Alzheimer's Disease)之主因，亦為這些蛋白質中相當重要之一種。 文獻顯示，類澱粉β蛋白質-細胞膜間交互作用與類澱粉β蛋白質誘發之神經毒性高度相關。研究亦發現，此交互作用可能受靜電作用力或細胞膜流動性所影響。然而，確定主宰此類澱粉β蛋白質與細胞膜間交互作用之機制至今仍無定論。 本研究提出：類澱粉β蛋白質-細胞膜間交互作用受與細胞膜性質息息相關之偶極電位(dipole potential)所影響之假說。認為偶極電位之變化反映類澱粉β蛋白質與細胞膜間之結合(binding)情形，而更進一步影響到誘發之毒性機制。因此吾人利用電場敏感性染劑(potential-sensitive fluorescent dye)配合雙波長螢光比值檢測法(dual-wavelength ratiometric fluorescence method)，量測細胞膜偶極電位受不同實驗條件變化之影響；並進一步觀察細胞膜偶極電位之改變，以對其間之交互作用作深入之探討與了解。結果顯示，當聚集狀態下之類澱粉症蛋白質與微脂粒作用時，可使其偶極電位下降；除此之外，添加膽固醇對於類澱粉β蛋白質所引起偶極電位下降之現象更加明顯。而吾人相信，本研究之結果可提供對於阿滋海默症及其他類澱粉症之機制更多的了解Up to now, at least twenty different human proteins and peptides have been isolated as the fibrillar components of disease-associated amyloid deposits. These proteins undergo aberrant changes in structure and accumulate to form aggregated species which lead to the amyloidogenic diseases. β-amyloid peptide (Aβ), the principal protein of Alzheimer’s disease, is also one of them. Previous studies showed that the interaction between Aβ and cell membrane is highly correlated to Aβ-elicited neurotoxicity. Several lines of evidence showed that the interaction between phospholipid membrane and Aβ might be associated with electrostatic-mediated forces or membrane fluidity. However, the detailed mechanism of this interaction remains largely unknown. In this work, we proposed a hypothesis that there is a link between membrane dipole potential and Aβ-cell membrane interaction, which is considered to be the first step in the mechanism of Aβ-induced toxicity and wish to test this hypothesis. To pursue our goals, we employed a dual-wavelength ratiometric fluorescence method with aid of the potential-sensitive fluorescent dye. At the outset, we sought out the optimal experimental conditions of the aforementioned ratiometric method. Next, we investigated the effect of binding of amyloid proteins and phospholipid vesicle on membrane dipole potential. Our results indicated that a decrease in dipole potential was observed upon binding of aggregated amyloid proteins to phospholipid membrane. In addition, a more dramatic change in membrane dipole potential was detected in phospholipid vesicles with cholesterol. We believe that our outcome may contribute to a better understanding of the mechanism(s) associated with AD and other amyloid diseases.第一章 緒論 1 第二章 文獻回顧 3 2-1 阿滋海默症(Alzheimer’s disease, AD)介紹 3 2-1-1 類澱粉症(Amyloidosis) 3 2-1-2 失智(dementia)與阿滋海默症(Alzheimer’s disease, AD) 4 2-1-3 阿滋海默症的分類 7 2-1-4 阿滋海默症的主要成因假說 8 2-2 阿滋海默症與類澱粉β蛋白質(β-amyloid, Aβ) 10 2-2-1 類澱粉前驅蛋白(amyloid precursor protein) 10 2-2-2 類澱粉β蛋白質 14 2-3 類澱粉β蛋白質與細胞膜間之交互作用 26 2-3-1 自由基生成(free radical generation) 26 2-3-2 鈣離子濃度平衡(calcium homeostasis) 28 2-3-3 類澱粉β蛋白質對細胞膜流動性(membrane fluidity)的影響 30 2-3-4 離子通道生成(ion channels formation) 31 2-3-5 靜電作用力對類澱粉β蛋白質與細胞膜交互作用之影響 32 2-3-6 類澱粉β蛋白質與細胞膜交互作用總結 33 2-4 微脂粒(Liposome)介紹 33 2-4-1 微脂粒簡介 33 2-4-2 微脂粒的分類 35 2-4-3 微脂粒的製備方法 35 2-4-4 微脂粒的安定性 39 2-5 偶極電位(Dipole potential)介紹 42 2-5-1 細胞膜(cell membrane)簡介 42 2-5-2 膜電位(membrane potential)介紹 44 2-5-3 膜電位之測量方法 49 第三章 研究動機 52 第四章 實驗裝置、藥品與步驟 53 4-1 實驗裝置 53 4-2 藥品 54 4-3 實驗步驟 55 4-3-1 PBS (phosphate buffered saline)之製備 55 4-3-2 微脂粒之製備 56 4-3-3 類澱粉β蛋白質Aβ(25-35)之備製 56 4-3-4 類澱粉β蛋白質Aβ(1-40)之備製 57 4-3-5 確實形成聚集狀態之類澱粉β蛋白質Aβ(1-40)備製 57 4-3-6 溶菌酶(lysozyme)之備製 58 4-3-7 雙波長螢光比值檢測法(dual-wavelength ratiometric fluorescence method) 58 第五章 結果討論 65 5-1 雙波長螢光比值檢測法(dual-wavelength ratiometric fluorescence method) 66 5-2 靜置時間之影響 70 5-3 不同溶劑對R值的影響 80 5-4 不同微脂粒濃度對R值的影響 83 5-5 類澱粉β蛋白質片段Aβ(25-35) 對細胞膜偶極電位的影響 85 5-6 類澱粉β蛋白質片段Aβ(1-40)對細胞膜偶極電位的影響 89 5-7 溶菌酶(hen agg white lysozyme)對細胞膜偶極電位的影響 93 5-8 膽固醇(cholesterol)與各物種和細胞膜偶極電位的關係 96 5-9 聚集狀態(aggregation state)之測試 100 5-10 總結：各物種和細胞膜偶極電位的關係 112 第六章 結論與建議 119 第七章 參考文獻 12