Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Cavity ring-down spectroscopy based on a comb-locked optical parametric oscillator source.

Spectroscopy of molecules in the mid-infrared (MIR) region has important applications in various fields, such as astronomical observation, environmental detection, and fundamental physics. However, compared to that in the near-infrared, precision spectroscopy in the MIR is often limited by the light source and has not shown full potential in sensitivity. Here we report a cavity ring-down spectroscopy system using a tunable narrow-linewidth optical parametric oscillator, which fulfills the requirement of high sensitivity and high precision in the MIR region. The Lamb-dip spectrum of the N2O molecule at 2.7 µm was measured as a demonstration of spectroscopy in the MIR with kilohertz accuracy.

Seeded optical parametric oscillator light source for precision spectroscopy.

Precision spectroscopy of fundamental bands of molecules in the mid-infrared (MIR) region is of great interest in applications of trace detection and testing fundamental physics, where high-power and narrow-linewidth MIR lasers are needed. By using a frequency-stabilized near-infrared laser as a seed of the signal light of a continuous-wave optical parametric oscillator, we established a broadly tunable MIR light source that has an output power of several hundred milliwatts and a linewidth of a few tens of kilohertz. The MIR laser frequency drift was reduced to below 1 kHz by using an optical frequency comb to stabilize the frequency of the 1064 nm pumping laser. The performance of the light source was investigated and tested by measuring the saturated absorption spectroscopy of a few molecular transitions at 3.3 µm.

Comb-locked cavity ring-down spectroscopy with variable temperature.

Temperature dependence of molecular absorption line shape is important information for spectroscopic studies and applications. In this work, we report a comb-locked cavity ring-down spectrometer employing a cryogenic cooler to perform absorption spectroscopy measurements at temperatures between 40 K and 300 K. As a demonstration, we recorded the spectrum of the R(0) line in the (2-0) band of HD at 46 K. The temperature was also confirmed by the Doppler width of the HD line. Spectra of CH4 near 1.394 µm were also recorded in a wide temperature range of 70-300 K. Lower-state energies of methane lines were analyzed by fitting these spectra, which can be directly compared with the HITRAN and TheoReTS databases. Considerable deviations were observed, indicating the need to investigate the assignments of the methane lines in this region.

Determination of the Interval between the Ground States of Para- and Ortho-H_{2}.

Nuclear-spin-symmetry conservation makes the observation of transitions between quantum states of ortho- and para-H_{2} extremely challenging. Consequently, the energy-level structure of H_{2} derived from experiment consists of two disjoint sets of level energies, one for para-H_{2} and the other for ortho-H_{2}. We use a new measurement of the ionization energy of para-H_{2} [E_{I}(H_{2})/(hc)=124 417.491 098(31) cm^{-1}] to determine the energy separation [118.486 770(50) cm^{-1}] between the ground states of para- and ortho-H_{2} and thus link the energy-level structure of the two nuclear-spin isomers of this fundamental molecule. Comparison with recent theoretical results [M. Puchalski et al., Phys. Rev. Lett. 122, 103003 (2019)PRLTAO0031-900710.1103/PhysRevLett.122.103003] enables the derivation of an upper bound of 1.5 MHz for a hypothetical global shift of the energy-level structure of ortho-H_{2} with respect to that of para-H_{2}.

Prednisolone dose during treatment of tuberculosis might be a risk factor for mortality in patients with systemic lupus erythematosus: a hospital-based cohort study.

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006-2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

Dissociation Energy of the Hydrogen Molecule at 10

The ionization energy of ortho-H_{2} has been determined to be E_{I}^{o}(H_{2})/(hc)=124 357.238 062(25) cm^{-1} from measurements of the GK(1,1)-X(0,1) interval by Doppler-free, two-photon spectroscopy using a narrow band 179-nm laser source and the ionization energy of the GK(1,1) state by continuous-wave, near-infrared laser spectroscopy. E_{I}^{o}(H_{2}) was used to derive the dissociation energy of H_{2}, D_{0}^{N=1}(H_{2}), at 35 999.582 894(25) cm^{-1} with a precision that is more than one order of magnitude better than all previous results. The new result challenges calculations of this quantity and represents a benchmark value for future relativistic and QED calculations of molecular energies.

Multichannel continuous-wave fiber cavity ringdown gas sensing utilizing frequency-shifted interferometry.

We present a multichannel continuous-wave (CW) fiber cavity ringdown (FCRD) gas sensing method based on frequency-shifted interferometry (FSI). This scheme detects gas concentration by measuring the intensity decay rates of continuous light from different ringdown cavities in the spatial domain, unlike conventional FCRD techniques, which measure the decay rates of pulse light in the time domain. This method shares one CW light source, one slow detector, and one slow data collector. In order to illustrate the theory, acetylene gas concentration measurement in a two-channel FSI-FCRD system was experimentally conducted in the range of 0%-1%. A linear relation was established between concentration and absorption loss, which is proportional to the intensity decay rate, and the measurement resolutions of 3.871%/dB and 3.658%/dB were achieved, respectively. The results reveal that the proposed system has the advantages of low cost, high sensitivity, high precision, and good stability in multichannel gas detection.

Identification and characterization of a late gene encoded by grouper iridovirus 2L (GIV-2L).

Grouper iridovirus (GIV) belongs to the Ranavirus genus and is one of the most important viral pathogens in grouper, particularly at the fry and fingerling stages. In this study, we identified and characterized the GIV-2L gene, which encodes a protein of unknown function. GIV-2L is 1242 bp in length, with a predicted protein mass of 46.2 kDa. It displayed significant identity only with members of the Ranavirus and Iridovirus genera. We produced mouse monoclonal antibodies against the GIV-2L protein by immunizing mice with GIV-2L-His-tag recombinant protein. By inhibiting de novo protein and DNA synthesis in GIV-infected cells, we showed that GIV-2L was a late gene during the viral replication. Finally, immunofluorescence microscopy revealed that GIV-2L protein accumulated in both the nucleus and cytoplasm of infected cells. These results offer important insights into the pathogenesis of GIV.

Normalization of the single atom counting rate in an atom trap.

The single atom counting rate of a rare isotope and the loading rate of another stable isotope with an abundance over 10 orders of magnitude larger are measured in one atom trap. The linear correlation between the measured counting/loading rates is examined to determine the (84)Kr/(82)Kr and (85)Kr/(83)Kr ratios of a Kr gas sample. Experiments show that the relative uncertainty is reduced to 1.3% when the single atom counting rate of (85)Kr is normalized by the measured (83)Kr loading rate. The measurement of the normalized single atom counting rate can be used to determine extremely low (10(-16)-10(-11)) isotope abundance. This normalization method is robust and can also be applied in other atomic systems.

The 4ν(CH) overtone of 12C2H2: sub-MHz precision spectrum reveals perturbations.

The third CH stretching vibration overtone (4ν(CH)) of the acetylene molecule has been a prototype for intra-molecular dynamics studies. Using a sensitive cavity ring-down spectrometer calibrated with precise atomic transitions, the absolute line frequencies of 50 lines of this band have been determined with sub-MHz accuracy, or relatively 2 × 10(-9). The accuracy is also confirmed by the combination differences between the transitions sharing the same upper level. The improved accuracy, two orders of magnitude better than previous studies, allows us to reveal finer ro-vibrational couplings. Fitting of the rotational energies indicates that the J-dependent interactions take place after J > 7. The precise line positions present useful confinements to the models of the intra-molecular interactions of the acetylene molecule.

Cavity ring-down spectroscopy of Doppler-broadened absorption line with sub-MHz absolute frequency accuracy.

A continuous-wave cavity ring-down spectrometer has been built for precise determination of absolute frequencies of Doppler-broadened absorption lines. Using a thermo-stabilized Fabry-Pérot interferometer and Rb frequency references at the 780 nm and 795 nm, 0.1 - 0.6 MHz absolute frequency accuracy has been achieved in the 775-800 nm region. A water absorption line at 12579 cm(-1) is studied to test the performance of the spectrometer. The line position at zero-pressure limit is determined with an uncertainty of 0.3 MHz (relative accuracy of 0.8 × 10(-9)).

A comprehensive 4-year survey of adverse drug reactions using a network-based hospital system.

WHAT IS KNOWN AND OBJECTIVE: Spontaneous Adverse Drug Reaction Reporting Systems (ADRRS) provide early warnings or 'signals' for adverse drug reactions (ADRs). Our aim was to survey reports of ADRs made through our teaching-hospital-based pharmacovigilance system to identify the drugs most commonly associated with allergies and the types of immunological reactions reported. METHODS: Adverse drug reactions records were retrieved from our network-based electronic notification system. RESULTS AND DISCUSSION: Four hundred and seventy four reports of adverse drug effects were studied. 37.3% of the reactions were immune-mediated drug hypersensitivity reactions. True drug hypersensitivity reactions involving IgE-mediated drug allergies accounted for 15% of all reactions. Of the drug hypersensitivity reactions, more than half (67%) were morbilliform skin eruptions, whereas cases of urticaria accounted for 20%. Antibiotics (33% of cases) were the most commonly reported drug allergies, followed by non-steroidal anti-inflammatory drugs (13%) and anti-epileptic agents (10%). WHAT IS NEW AND CONCLUSIONS: A hospital-based ADR reporting system can generate useful data. In our study, antibiotics accounted for the majority of drug allergies, particularly anaphylactic reactions. More cases of drug allergies were owing to cephalosporin allergies than penicillins. Anti-epileptic agents caused most of the severe drug hypersensitivity syndromes.

Application of cavity ring-down spectroscopy to the Boltzmann constant determination.

The Boltzmann constant can be optically determined by measuring the Doppler width of an absorption line of molecules at gas phase. We propose to apply a near infrared cavity ring-down (CRD) spectrometer for this purpose. The superior sensitivity of CRD spectroscopy and the good performance of the near-ir lasers can provide ppm (part-per-million) accuracy which will be competitive to present most accurate result obtained from the speed of sound in argon measurement. The possible influence to the uncertainty of the determined Doppler width from different causes are investigated, which includes the signal-to-noise level, laser frequency stability, detecting nonlinearity, and pressure broadening effect. The analysis shows that the CRD spectroscopy has some remarkable advantages over the direct absorption method proposed before. The design of the experimental setup is presented and the measurement of C2H2 line near 0.8 µm at room temperature has been carried out as a test of the instrument.

Effects of the different frequencies of whole-body vibration during the recovery phase after exhaustive exercise.

AIM: This study was to investigate the effects of vibration exercise on the oxygen consumption (VO2) and heart rate variability (HRV) during the recovery phase after exhaustive exercise. METHODS: Twenty male college students volunteered as subjects to participate in the study. The subjects were randomly crossover assigned to perform three 10 min vibration exercises, namely non-vibration (CON, 0 Hz, 0 mm), low-frequency (LFT, 20 Hz, 0.4 mm) and high-frequency (HFT, 36 Hz, 0.4 mm) treatments immediately after an incremental exhaustive cycling exercise in separated days. The beat-to-beat HRV, blood lactate concentration and VO2 were measured during the 1-hour recovery phase. The time- and frequency-domain indices of HRV were analyzed to confirm the effects of vibration exercises on the cardiac autonomic modulation. RESULTS: There were no significant differences on the VO2, HRV and blood lactate concentrations at 30th minute (post-30 min) or 60th minute (post-60 min) during the recovery phase among the three treatments. There were also no significant differences on the excess post-exercise oxygen consumption (EPOC) during the recovery phase among the treatments. However, the VO2 at post-30 min in CON and LFT were significantly higher than the baseline values, whereas the VO2 in HFT returned to resting condition at the post-30 min. CONCLUSIONS: The results indicate that both low and high frequency vibration exercises could not improve the physiological recovery after exhaustive cycling exercise. However, the high frequency vibration exercise probably has a potential to facilitate the VO2 to return to the resting level during the recovery phase.

Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy.

Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with alpha-actinin or other Z-line components. These results suggest that Cypher functions as a linker-strut to maintain cytoskeletal structure during contraction.

Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.

The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM-1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer-dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites.

Purification and characterization of rat heart and brain catechol methyltransferase.

In an effort to detect the similarities and differences in the properties of rat heart, brain and liver catechol methyltransferase (S-adenosyl-L-methionine:catechol O-methyltransferase, EC 2.1.1.6), we have determined the cellular distribution of this enzyme activity and extensively purified the soluble and microsomal enzymes present in these tissues. Purification of soluble heart (688-fold) and brain enzymes (240-fold) were achieved using an affinity chromatographic system. The properties of these enzymes were compared with respect to their molecular weights, substrate specificities, inhibitor specificities and immunological properties. The characteristics of the enzyme active sites were investigated using various methyl acceptor substrates and various analogs of S-adenosylmethionine as methyl donors. A series of analogs of S-adenosylhomocysteine was also evaluated as inhibitors of these enzymes. The immunological properties of the purified soluble and microsomal enzymes from heart and brain were investigated using an antibody isolated from rabbits which had been immunized with the soluble rat liver enzyme. In general the properties of catechol methyltransferases isolated from heart and brain were similar to the properties of the enzyme isolated from liver. Some minor differences in substrate and inhibitor specificities were observed which might suggest slight differences in the active sites of these enzymes.

Evolution of coronary artery pattern according to short-axis aortopulmonary rotation: a new categorization for complete transposition of the great arteries.

OBJECTIVES: We studied the correlation between coronary artery pattern and aortopulmonary rotation in complete transposition of the great arteries. BACKGROUND: Classifications of the coronary arteries in complete transposition are puzzling and incomplete. METHODS: Coronary artery anatomy and relation of the great arteries were identified at angiography, echocardiography, surgical intervention or autopsy in 76 patients with complete transposition from 1988 to 1993. Five main types (type 0 and Shaher types 1,2,4 and 9) and their similar variants of epicardial configuration were categorized into five patterns (O, I, II, IV and IX). In addition, data from 568 cases from published reports were collected for analysis. RESULTS: As the aorta rotated from a left anterior to a directly anterior location relative to the pulmonary trunk, the left anterior descending coronary artery arose from the left-hand sinus together with the right coronary artery (type 0, one case decreased to no cases); then it gradually shifted to the left to have the same origin as the left circumflex coronary artery from the right-hand sinus (type 1, 10 cases increased to 146, p < 0.0003). When the aorta rotated farther clockwise from directly anterior to right anterior (type 1, 146 cases increased to 235; type 2, 9 cases increased to 50, p < 0.0006) or from right anterior to right lateral (type 1, 235 cases decreased to 6 cases; type 2, 50 cases decreased to 20, p < 0.00000), the left circumflex coronary artery tended to move retropulmonically and originated from the left-hand sinus with the right coronary artery (type 2). When the aorta moved from right anterior to right lateral (type 2, 50 cases decreased to 20; type 4, 13 cases increased to 14, p < 0.031) or from right lateral to right posterior (type 2, 20 cases decreased to 1; type 4, 14 cases increased to 16, p < 0.0003), the right coronary artery shifted to the right-hand sinus anteaortically to join the left anterior descending coronary artery (type 4). Finally, the left anterior descending coronary artery combined with the left circumflex coronary artery (type 9, 12 cases increased to 21, p = 0.407) to become the usual pattern for normally related great arteries. Eta-square analysis showed that the evolution from pattern O to IX was dependent on clockwise aortopulmonary rotation. CONCLUSIONS: The coronary arteries in complete transposition of the great arteries can be classified into five patterns and their evolution deduced on the basis of aortopulmonary rotation. Dependence of coronary artery type on aortopulmonary rotation made it possible to anticipate the coronary pattern from the relation of the great arteries in transposition.