Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome

Long QT syndrome (LQTS) is characterized by QT prolongation, syncope and sudden death. This study aims to explore the causes, clinical manifestations and therapeutic outcomes of Jervell and Lange-Nielsen syndrome (JLNS), a rare form of LQTS with congenital sensorineural deafness, in Chinese individuals.Three JLNS kindreds from the Chinese National LQTS Registry were investigated. Mutational screening of KCNQ1 and KCNE1 genes was performed by polymerase chain reaction and direct DNA sequence analysis. LQTS phenotype and therapeutic outcomes were evaluated for all probands and family members.We identified 7 KCNQ1 mutations. c.1032_1117dup (p.Ser373TrpfsX10) and c.1319delT (p.Val440AlafsX26) were novel, causing JLNS in a 16-year-old boy with a QTc (QT interval corrected for heart rate) of 620 ms and recurrent syncope. c.605-2A>G and c.815G>A (p.Gly272Asp) caused JLNS in a 12-year-old girl and her 5-year-old brother, showing QTc of 590 to 600 ms and recurrent syncope. The fourth JLNS case, a 46-year-old man carrying c.1032G>A (p.Ala344Alasp) and c.569G>A (p.Arg190Gln) and with QTc of 460 ms, has been syncope-free since age 30. His 16-year-old daughter carries novel missense mutation c.574C>T (p.Arg192Cys) and c.1032G>A(p.Ala344Alasp) and displayed a severe phenotype of Romano-Ward syndrome (RWS) characterized by a QTc of 530 ms and recurrent syncope with normal hearing. Both the father and daughter also carried c.253G>A (p.Asp85Asn; rs1805128), a rare single nucleotide polymorphism (SNP) on KCNE1. Bizarre T waves were seen in 3/4 JLNS patients. Symptoms were improved and T wave abnormalities became less abnormal after appropriate treatment.This study broadens the mutation and phenotype spectrums of JLNS. Compound heterozygous KCNQ1 mutations can result in both JLNS and severe forms of RWS in Chinese individuals.SCI(E)CPCI-S(ISTP)PubMed0MEETING ABSTRACT267-75

Quantification and recognition of parkinsonian gait from monocular video imaging using kernel-based principal component analysis

<p>Abstract</p> <p>Background</p> <p>The computer-aided identification of specific gait patterns is an important issue in the assessment of Parkinson's disease (PD). In this study, a computer vision-based gait analysis approach is developed to assist the clinical assessments of PD with kernel-based principal component analysis (KPCA).</p> <p>Method</p> <p>Twelve PD patients and twelve healthy adults with no neurological history or motor disorders within the past six months were recruited and separated according to their "Non-PD", "Drug-On", and "Drug-Off" states. The participants were asked to wear light-colored clothing and perform three walking trials through a corridor decorated with a navy curtain at their natural pace. The participants' gait performance during the steady-state walking period was captured by a digital camera for gait analysis. The collected walking image frames were then transformed into binary silhouettes for noise reduction and compression. Using the developed KPCA-based method, the features within the binary silhouettes can be extracted to quantitatively determine the gait cycle time, stride length, walking velocity, and cadence.</p> <p>Results and Discussion</p> <p>The KPCA-based method uses a feature-extraction approach, which was verified to be more effective than traditional image area and principal component analysis (PCA) approaches in classifying "Non-PD" controls and "Drug-Off/On" PD patients. Encouragingly, this method has a high accuracy rate, 80.51%, for recognizing different gaits. Quantitative gait parameters are obtained, and the power spectrums of the patients' gaits are analyzed. We show that that the slow and irregular actions of PD patients during walking tend to transfer some of the power from the main lobe frequency to a lower frequency band. Our results indicate the feasibility of using gait performance to evaluate the motor function of patients with PD.</p> <p>Conclusion</p> <p>This KPCA-based method requires only a digital camera and a decorated corridor setup. The ease of use and installation of the current method provides clinicians and researchers a low cost solution to monitor the progression of and the treatment to PD. In summary, the proposed method provides an alternative to perform gait analysis for patients with PD.</p

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

A molecular dynamics study on the CO2 permeability of microalgae lipid membrane

Reducing the amount of carbon emissions has been a formidable challenge especially to countries experiencing rapid economic growth. This prompted the development of various materials and methodologies to capture emissions to address climate change. The current study aimed to contribute in the development of carbon dioxide capture through the biological approach by using microorganisms such as microalgae. Biological fixation involving microalgae involves a complex process that has not been fully understood as current experimental methods can only deliver analysis on a macroscopic scale. The study demonstrated the dynamics of carbon dioxide molecules in the atomic scale using molecular dynamics. The permeation coefficient of carbon dioxide molecules was calculated at different range of temperature and salinity using the inhomogeneous solubility diffusion model. The GROMOS53a6 and SPC force field was used for the interaction of molecules. Moreover, the force autocorrelation function was used to calculate the diffusion coefficient. The resulting diffusion coefficients were in a good agreement with experimental data. The highest permeation coefficient of 2.3994 × 10−3 cm s−1 was calculated at 330 K 0.55 M conditions. Due to the nonpolar nature of carbon dioxide molecule, the mobility as it permeates inside the bilayer was not affected. Hence, the study suggests that the temperature and salinity does not prevent nor significantly affects the permeability of microalgae lipid membrane from carbon dioxide molecules. © 2019, Springer Nature B.V

Effect of Pore Confinement of NaNH2 and KNH2 on Hydrogen Generation from Ammonia

The development of efficient catalysts for hydrogen generation via ammonia decomposition is crucial for the use of ammonia as an energy carrier. Here, we report the effect of pore confinement of NaNH2 and KNH2 on ammonia decomposition catalysis. For the first time, Ni- or Ru-doped NaNH2 and KNH(2 )were confined in carbon nanopores using a combination method of solution impregnation and melt infiltration. Structure characterization indicates the nanoscale intimacy between transition metals and alkali metal amides inside the pores of the carbon support. As a result, 8 wt % Ni-doped NaNH2 and KNH2 nanocomposites give NH3 conversions of 79 and 60%, respectively at 425 degrees C, close to the performance of a 5 wt % Ru/C reference catalyst. 0.8 wt % Rudoped nanocomposites exhibit even better catalytic performance, with about 95% NH3 conversion at a moderate temperature of 375 degrees C. The hydrogen production rates of these Ni- and Ru-doped nanocomposites in a pure NH3 flow are about 3-4 times higher than for the recently reported novel catalysts such as Ni-Li2NH and Ru-Li2NH/MgO. Interestingly, the apparent activation energies of the Ru- or Ni-based catalysts decrease 20-30 kJ mol(-1) alkali metal amides. The strategy of nanoconfinement of alkali metal amides in porous hosts may effectively generating H-2 from NH3 at low temperatures

Effect of Pore Confinement of NaNH2 and KNH2 on Hydrogen Generation from Ammonia

The development of efficient catalysts for hydrogen generation via ammonia decomposition is crucial for the use of ammonia as an energy carrier. Here, we report the effect of pore confinement of NaNH2 and KNH2 on ammonia decomposition catalysis. For the first time, Ni- or Ru-doped NaNH2 and KNH2 were confined in carbon nanopores using a combination method of solution impregnation and melt infiltration. Structure characterization indicates the nanoscale intimacy between transition metals and alkali metal amides inside the pores of the carbon support. As a result, 8 wt % Ni-doped NaNH2 and KNH2 nanocomposites give NH3 conversions of 79 and 60%, respectively at 425 °C, close to the performance of a 5 wt % Ru/C reference catalyst. 0.8 wt % Ru-doped nanocomposites exhibit even better catalytic performance, with about 95% NH3 conversion at a moderate temperature of 375 °C. The hydrogen production rates of these Ni- and Ru-doped nanocomposites in a pure NH3 flow are about 3-4 times higher than for the recently reported novel catalysts such as Ni-Li2NH and Ru-Li2NH/MgO. Interestingly, the apparent activation energies of the Ru- or Ni-based catalysts decrease 20-30 kJ mol-1 by co-confinement with alkali metal amides. The strategy of nanoconfinement of alkali metal amides in porous hosts may open a new avenue for effectively generating H2 from NH3 at low temperatures

Relationship Between Blood and Tissue-Based Rejection-Related Transcripts in Heart Transplantation.

PURPOSE: The purpose of the study is to investigate the relationship between blood and tissue-derived rejection-related transcripts from blood gene expression profiling (GEP) and molecular microscope in the setting of allograft rejection in heart transplant. METHODS: All heart transplant patients from August 2021 to May 2022 with both circulating blood GEP (AlloMap; CareDx) and endomyocardial biopsy with molecular microscope diagnostic system (MMDx, One Lambda) within 4 weeks were included (N=173 samples). We obtained individual blood GEP-based mRNA transcript expression levels of the 11 target genes from CareDx. Student\u27s t-test was performed to compare blood GEP transcript expression levels between no rejection and rejection as assessed by MMDx. A Scatter plot with Spearman correlation analysis was performed to compare the relationship between transcript expression levels from AlloMap and MMDx, with and without allograft rejection. RESULTS: There were 52 samples (30.1%) with antibody-mediated rejection (ABMR) and 15 samples (8.7%) with T-cell-mediated rejection (TCMR), as assessed by MMDx. Expression of one of the blood ITGA4 (Integrin alpha 4) expression level was elevated in ABMR, compared to no ABMR (4607.5 vs 4217.5; p=0.019). Most tissue RAT expression levels were elevated in ABMR, and tissue ROBO4 expression correlated with the blood ITGA4 expression with moderate or greater effect size in all samples (Spearman\u27s R 0.31; p DISCUSSION: Circulating blood ITGA4 expression is elevated in AMR and correlate with myocardial expression of ROBO4. The knowledge of individual transcript expression levels in blood and in tissue may provide insights into various disease processes in heart transplant patients. Taken together, the results of our study reveal an overlap between two objective post-heart transplant rejection surveillance methods, identify potential novel markers for ABMR, and reveal the need for a deeper understanding of molecular mechanisms underlying allograft rejection

Thrombolytics for venous thromboembolic events: a systematic review with meta-analysis

Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics