A new score system for predicting response to cardiac resynchronization therapy

Background: The aim of this study was to establish a score system derived from clinical, echocardiographic and electrocardiographic indexes and evaluate its clinical value for cardiac resynchronization therapy (CRT) patient selection. Methods: Ninety-three patients receiving CRT were enrolled. A patient selection score system was generated by the clinical, echocardiographic and electrocardiographic parameters achieving a significant level by univariate and multivariate Cox regression model. The positive response to CRT was a left ventricular end systolic volume decrease of ≥ 15% and not reaching primary clinical endpoint (death or re-hospitalization for heart failure) at the end of follow-up. Results: Thirty-nine patients were CRT non-responders (41.94%) and 54 were responders (58.06%). A 4-point score system was generated based on tricuspid annular plane systolic ex­cursion (TAPSE), longitudinal strain (LS), and complete left bundle branch block (CLBBB) combined with a wide QRS duration (QRSd). The sensitivity and specificity for prediction of a positive response to CRT at a score > 2 were 0.823 and 0.850, respectively (AUC: 0.92295% CI 0.691–0.916, p< 0.001). Conclusions: A patient selection score system based on the integration of TAPSE, LS and CLBBB combined with a wide QRSd can help to predict positive response to CRT effectively and reliably

The Bantam microRNA Is Associated with Drosophila Fragile X Mental Retardation Protein and Regulates the Fate of Germline Stem Cells

Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). We have previously demonstrated that dFmr1, the Drosophila ortholog of the fragile X mental retardation 1 gene, plays a role in the proper maintenance of germline stem cells in Drosophila ovary; however, the molecular mechanism behind this remains elusive. In this study, we used an immunoprecipitation assay to reveal that specific microRNAs (miRNAs), particularly the bantam miRNA (bantam), are physically associated with dFmrp in ovary. We show that, like dFmr1, bantam is not only required for repressing primordial germ cell differentiation, it also functions as an extrinsic factor for germline stem cell maintenance. Furthermore, we find that bantam genetically interacts with dFmr1 to regulate the fate of germline stem cells. Collectively, our results support the notion that the FMRP-mediated translation pathway functions through specific miRNAs to control stem cell regulation

Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40

BACKGROUND: Alzheimer’s disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ(42) ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ(42)) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers. METHODS: We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer’s Disease Research Center. We tested correlations between YKL-40 and CSF Tau/Aβ(42) ratio, Aβ(42), tau, and phosphorylated tau (ptau(181)). We used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts from the most significant locus to adjust YKL-40 values and tested the differences in correlations with CSF Tau/Aβ(42) ratio, Aβ(42), tau, and ptau(181). RESULTS: We found that genetic variants on the CH13L1 locus were significantly associated with CSF YKL-40 levels, but not AD risk, age at onset, or disease progression. The most significant variant is a reported expression quantitative trait locus for CHI3L1, the gene which encodes YKL-40, and explained 12.74 % of the variance in CSF YKL-40 in our study. YKL-40 was positively correlated with ptau(181) (r = 0.521) and the strength of the correlation significantly increased with the addition of genetic information (r = 0.573, p = 0.006). CONCLUSIONS: CSF YKL-40 levels are likely a biomarker for AD, but we found no evidence that they are an AD endophenotype. YKL-40 levels are highly regulated by genetic variation, and by including genetic information the strength of the correlation between YKL-40 and ptau(181) levels is significantly improved. Our results suggest that studies of potential biomarkers may benefit from including genetic information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12883-016-0742-9) contains supplementary material, which is available to authorized users

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection

Background and objectivesDisease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms.MethodsCOVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers.ResultsThe oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway.ConclusionThe oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10-8) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10-8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10-2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10-2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10-3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies

Video-assisted thoracoscopic right upper lobectomy in a patient with a right-sided aortic arch and Kommerell diverticulum

Abstract Background It is a very rare condition for a patient to have right lung cancer and a right-sided aortic arch simultaneously. Right lobectomy under video-assisted thoracoscopic surgery (VATS) in such a patient is a challenging procedure that is seldom reported. We successfully performed a VATS right upper lobectomy in a 77-year-old female with a right-sided aortic arch and Kommerell diverticulum. Case presentation A 77-year-old woman was referred to our division for a mixed ground-glass opacity lesion in the right upper lung. A right-sided aortic arch with Kommerell diverticulum was identified by preoperative 3D CT reconstruction. A VATS right upper lobectomy with radical mediastinal lymph node dissection was performed, and the final histological staging was Ia3 (pT1cN0M0). The patient was discharged without any complications. Conclusions We conclude that the video-assisted thoracic surgery can be safely performed in such conditions. It is difficult to determine the extent of upper mediastinal lymph node dissection in such cases

Physicochemical Properties and Cookie-Making Performance as Fat Replacer of Wax-Based Rice Bran Oil Oleogels

Reducing the intake of trans and saturated fatty acids is a trend in healthy eating. In this study, the oleogels were prepared from rice bran oil (RBO), candle wax (CDW), beeswax (BW), rice bran wax (RBW), and carnauba wax (CRW), respectively, and the results based on their physicochemical properties and crystal structures at critical concentrations, 6 wt.%, 8 wt.%, and 10 wt.%, were determined to further investigate the oleogels as a shortening substitute in cookie recipes. Oleogel has a smooth, spreadable β′ crystal shape which creates excellent sensory properties and improves the texture, but also has some economic benefits. A comparison between the oleogels formed at critical concentrations and those with improved mass fractions was performed in several analyses such as PLM and texture, and the oleogels with higher mass fractions had a greater hardness and stickiness and denser crystal structures. This study was used to optimize the cookie recipe by partially replacing shortening with oleogel and preparing the cookies according to the 0:1, 3:7, 1:1, 7:3, 1:0 oleogel shortening mixture, respectively. Based on the results of the textural analysis, a colorimetric and sensory evaluation of the optimized formulation of oleogels in cookies, it was evident that BW and RBW oleogels have more potential to replace shortening in cookies than CDW and CRW oleogels. In particular, oleogels with a concentration of 6 wt.% RBW (RBW-6) and at a 7:3 (oleogel:shortening) shortening replacement exhibited a hardness and crispness of 15.75 N and 97.73 g, respectively, with an L* value of 66.66 and a sensory score of 22.32 ± 0.09. The value for the color perception difference (dE) between the cookies and the control group was −3.73, which allowed us to obtain a good product with a quality and characteristics similar to shortening. This supports the feasibility of new solid fats to replace traditional plastic fats in baked goods

Effect of Solidified Depth on the Vertical Compressive Bearing Characteristics of the Soil Continuously Solidified Pile Group Foundation

To meet the ultra-high bearing capacity design requirements of pile foundations under geological conditions without a good holding layer, we invented a new type of group pile foundation with the soil continuously solidified between piles (hereinafter referred to as the SCS group pile foundation). Considering the solidified depth as a key influencing factor, the vertical ultimate compressive bearing capacity, load transfer law, and damage pattern of the soil around the continuously solidified group pile foundation were investigated using an indoor half-model test. The results revealed that the setting of the continuously solidified part has a significant effect on its compressive bearing characteristics. The ultimate compressive bearing capacity of the SCS group pile foundation was increased by four to nine times compared with the traditional group pile foundation. When the pile spacing is 4–6D (D = pile diameter), designing a continuously solidified depth greater than 14D is recommended. Except for the solidified depths of 2D and 18D, the lateral resistances of the other model piles first increase and then decrease with increasing depth. The maximum values were located at the continuously solidified part and were obviously larger than those of the other pile sections. The maximum pile lateral frictional resistance was provided at the maximum depth of the continuously solidified part. After setting up the continuously solidified part, none of the bearing capacity of the pile ends exceeded 5%. The bearing capacity of the SCS group pile foundation was mainly shared by the continuously solidified part and the pile lateral frictional resistance. For the same pile spacing, the high strain damage zone of the soil at the bottom of the continuously solidified 2D–14D foundation was “abacus bead”; when the burial depth of the continuously solidified part reached 18D, the foundation soil exhibited “inverted bowl” damage