Machine learning prediction of hypertension and diabetes in twin pregnancies using characteristics at prenatal care entry: a nationwide study.

OBJECTIVES: To develop a prediction model for hypertensive disorders in pregnancy (HDP) and gestational diabetes (GDM) in twin pregnancies utilizing characteristics at the prenatal care entry level. METHODS: Cross-sectional study using the US national live birth data between 2016 and 2021. The association of all prenatal candidate variables with HDP and GDM was tested with uni- and multi-variable logistic regression analyses. Prediction models were built with generalized linear models using the logit link function and classification and regression tree approach (XGboost) machine learning (ML) algorithm. Performance was assessed with repeated 2-fold cross-validation and performance metrics we considered were area under the curve (AUC). P value <0.001 was considered statistically significant. RESULTS: A total of 707,198 twin pregnancies were included in the HDP analysis and 723,882 twin pregnancies for the GDM analysis. The incidence of HDP and GDM significantly increased from 12.2% in 2016 to 15.4% in 2021 and from 8.1% in 2016 to 10.7% in 2021, respectively. Factors that increase the risk of HDP in twin gestations are maternal age <20, age≥35, infertility, prepregnancy DM, non-Hispanic Black population, obesity, and those with Medicaid insurance (p<0.001). Factors that more than doubled the risk are obesity class II and III (p<0.001). Factors that increase the risk of GDM in twin gestations are age <25, age≥30, history of infertility, prepregnancy hypertension, non-Hispanic Asian population, non-US nativity, and obesity (p<0.001). Factors that more than doubled the risk are maternal age ≥ 30 years, non-Hispanic Asian, and class I, II, and III maternal obesity ( p<0.001). For both HDP and GDM, the performance of the ML and logistic regression model was mostly similar with negligible difference in terms of all tested performance domains. The AUC of the final ML model for HDP and GDM were 0.62±0.004, and 0.67±0.004, respectively. CONCLUSIONS: The incidence of HDP and GDM in twin gestations is increasing. The predictive accuracy of the machine learning model for both HDP and GDM in twin gestations is similar to that of the logistic regression model. Both models had modest performance, well-calibrated, and neither had a poor fit. This article is protected by copyright. All rights reserved.

Diagnostic yield of exome sequencing in prenatal agenesis of corpus callosum: systematic review and meta-analysis.

OBJECTIVES: To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants. METHODS: A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided for two of them. The increase in diagnostic yield with ES for pathogenic/likely pathogenic (P/LP) variants was assessed in all cases of ACC, isolated ACC, ACC with other cranial anomalies and ACC with extracranial anomalies. To identify all reported genetic variants, the systematic review included all ACC cases; however, for the meta-analysis, only studies with ≥ three ACC cases were included. Meta-analysis of proportions was employed using a random-effects model. Quality assessment of the included studies was performed using modified Standards for Reporting of Diagnostic Accuracy criteria. RESULTS: A total of 28 studies, encompassing 288 prenatally diagnosed ACC cases that underwent ES following negative CMA, met the inclusion criteria of the systematic review. We classified 116 genetic variants in 83 genes associated with prenatal ACC with a full phenotypic description. There were 15 studies, encompassing 268 cases, that reported on ≥ three ACC cases and were included in the meta-analysis. Of all the included cases, 43% had a P/LP variant on ES. The highest yield was for ACC with extracranial anomalies (55% (95% CI, 35-73%)), followed by ACC with other cranial anomalies (43% (95% CI, 30-57%)) and isolated ACC (32% (95% CI, 18-51%)). CONCLUSIONS: ES demonstrated an incremental diagnostic yield in cases of prenatally diagnosed ACC following negative CMA. While the greatest diagnostic yield was observed in ACC with extracranial anomalies and ACC with other central nervous system anomalies, ES should also be considered in cases of isolated ACC. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal lower urinary tract obstruction: international Delphi consensus on management and core outcomes set.

OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO). METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS. RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon. CONCLUSION: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.

Evaluation of temporomandibular joint morphology and morphometry in male osteoporotic patients using advanced imaging and biochemical markers: A cross-sectional study.

Osteoporosis is a condition with reduced bone mass and disrupted architecture. Osteoporosis affects the Temporomandibular disorders (TMD) by changing bone density and quality. This study aims to determine the nature and extent of temporomandibular joint (TMJ) involvement in osteoporotic patients by correlating TMJ morphological changes detected by CBCT with systemic bone health indicated by BMD T-scores from DEXA and analyzing BTMs in serum and saliva. This study was a cross-sectional study conducted from May 2021 to December 2022. It involved 50 participants divided into two groups (N=25). One group was healthy male, while the other group had osteoporosis male. Saliva and blood samples were collected, and diagnostic imaging was conducted. The prevalence of various bone changes in the condyle was examined using CBCT. Erosion was found to be the most common, followed by Flattening, Osteophyte, and Subchondral cysts. The study group had significantly higher rates of smooth condyle, erosive lesions, and osteophytes compared to the control group. Pseudocyst decreased on the right side but increased on the left side. Pain on the right side increased more in the study group, and the T score for osteoporosis was higher in the study group. Joint spaces, condyle diameter, and glenoid cavity measurements differed significantly between sick and healthy people, as shown by CBCT (P≤0.001). Only the ALP parameter in the serum showed a significant increase in the study group compared to the control group. Saliva analysis revealed higher levels of calcium, osteocalcin, and ALP in the case group compared to the control group. The results of this study showed that CBCT as a specialized technique in imaging by providing detailed images can be used to evaluate osteoporosis and be used as an accurate diagnostic tool.

Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.

Prediction of dual survival following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To develop a model based on factors available at the time of diagnosis of twin-twin transfusion syndrome (TTTS) for predicting the probability of dual twin survival following fetoscopic laser photocoagulation (FLP) using a machine-learning algorithm. METHODS: This was a retrospective study of data collected at two university-affiliated tertiary fetal centers between 2012 and 2021. The cohort included monochorionic diamniotic twin pregnancies complicated by TTTS that underwent FLP. Data were stratified based on survival 30 days after delivery, and cases with dual survival were compared to those without dual survival. A random forest machine-learning algorithm was used to construct a prediction model, and the relative importance value was calculated for each parameter that presented a statistically significant difference between the two study groups and was included in the model. The holdout method was applied to check overfitting of the random forest algorithm. A prediction model for dual twin survival 30 days after delivery was presented based on the test set. RESULTS: The study included 537 women with monochorionic diamniotic twin pregnancy, of whom 346 (64.4%) had dual twin survival at 30 days after delivery and were compared with 191 (35.6%) cases that had one or no survivors. Univariate analysis demonstrated no differences in demographic parameters between the groups. At the time of diagnosis, the dual-survival group had lower rates of estimated fetal weight (EFW) < 10th centile for gestational age in the donor twin (56.4% vs 69.4%; P = 0.004), intertwin EFW discordance > 25% (40.8% vs 56.5%; P = 0.001) and anterior placenta (40.5% vs 50.0%; P = 0.034). Comparison of Doppler findings between the two groups demonstrated significant differences in the donor twin, with a lower rate of pulsatility index (PI) > 95th centile in the umbilical artery and ductus venosus and a lower rate of PI < 5th centile in the fetal middle cerebral artery in the dual-survival group. Relative importance values for each of these six parameters were calculated, allowing the construction of a prediction model with an area under the receiver-operating-characteristics curve of 0.916 (95% CI, 0.887-0.946). CONCLUSIONS: We developed a predictive model for dual survival in monochorionic twin pregnancies following FLP for TTTS, which incorporates six variables obtained at the time of diagnosis of TTTS, including donor EFW < 10th centile, intertwin EFW discordance > 25%, anterior placenta and abnormal PI in the umbilical artery, ductus venosus and middle cerebral artery of the donor twin. This clinically applicable tool may improve treatment planning and patient counseling. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Management of menopause: a survey of physicians from the Middle East and Africa.

OBJECTIVE: This study evaluated physicians' perceptions, practices, confidence, comfort level and prior training in managing menopause. METHODS: A survey was conducted of a convenience sample of physicians from the Middle East and Africa (MEA) in 2019. We covered knowledge of symptoms, menopausal hormone therapy (MHT), other menopause management strategies and prior training in menopause medicine. RESULTS: Of the 254 participants, 64.2% were seniors in family medicine (36.4%), endocrinology (36.0%), gynecology (15.8%) and internal medicine (13.8%). Fewer than one-third (28.8%) correctly identified the diagnostic criteria of menopause. Almost all recognized vasomotor symptoms (99.5%), vaginal dryness (96.2%) and mood disturbance (94.3%), but to a lesser extent other symptoms. Inconsistency and critical gaps were identified in responses to competence questions on six case studies. They recalled having occasional (43.2%) or no training (19.4%) in menopause medicine and rated their preparedness to treat menopause widely. A total of 66.2% agreed that training is very important. Variation between specialties was identified. CONCLUSION: Many physicians recognize the importance of education in menopause management, but their responses revealed critical knowledge gaps that underscored the need for comprehensive, evidence-based menopause management.

Effects of "defective" plasmonic metal nanoparticle arrays on the opto-electronic performance of thin-film solar cells: computational study.

This computational study investigates the effects of common defects that occur while fabricating arrays of plasmonic metal nanoparticles (NPs) on the absorbing layer of the solar cells for enhancing their opto-electronic performance. Several "defects" in an array of plasmonic NP arrays on solar cells were studied. The results demonstrated no major changes in the performance of solar cells in the presence of "defective" arrays when compared to a "perfect" array with defect-free NPs. The results indicate that relatively inexpensive techniques may be used to fabricate "defective" plasmonic NP arrays on solar cells and still obtain a significant enhancement in opto-electronic performance.

Efficacy of long-term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin-to-twin transfusion syndrome: a collaborative cohort study.

OBJECTIVE: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Collaborative multicentre study. POPULATION: Five hundred and fifty-seven consecutive TTTS cases that underwent FLS. METHODS: Long-term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. MAIN OUTCOME MEASURES: Gestational age (GA) at delivery. RESULTS: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non-LIT group (31.1 weeks; P < 0.001). FLS-to-delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non-LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. CONCLUSION: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. TWEETABLE ABSTRACT: Long-term indomethacin used after fetoscopic laser surgery for twin-to-twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth.

Perinatal outcomes of fetoscopic laser surgery for twin-twin transfusion syndrome in triplet pregnancy: cohort study, systematic review and meta-analysis.

OBJECTIVES: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population. METHODS: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth. RESULTS: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets. CONCLUSIONS: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Iatrogenic chorioamniotic separation and septostomy following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To compare the perinatal outcomes of pregnancies complicated by chorioamniotic separation (CAS) vs septostomy following fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort analysis of monochorionic diamniotic twin pregnancies with TTTS that underwent FLP at one of two university-affiliated tertiary medical centers between January 2012 and December 2020. CAS and septostomy were diagnosed either during the procedure or by ultrasonography within 24-48 h after FLP. Data on procedure and postprocedure parameters, pregnancy outcomes and survival were collected from the patients' electronic medical records. Pregnancies were stratified according to the presence of CAS, septostomy or neither. Patients diagnosed with both CAS and septostomy were analyzed separately. RESULTS: Of the 522 women included in the cohort, 38 (7.3%) were diagnosed with CAS, 68 (13.0%) with septostomy and 23 (4.4%) with both CAS and septostomy. The remaining 393 (75.3%) women comprised the control group. Groups did not differ in demographic characteristics. The septostomy group had a lower rate of selective fetal growth restriction than did the CAS and control groups (24.2% vs 36.8% vs 42.7%, respectively; P = 0.017). Moreover, intertwin size discordance was lower in the septostomy group (15.1% vs 23.4% in the CAS group and 25.5% in the control group; P = 0.001). Median gestational age at FLP was significantly lower in the CAS group (19.3 weeks vs 20.4 weeks in controls and 20.9 weeks in the septostomy group; P = 0.049). The rate of delivery prior to 34 weeks was significantly higher in the CAS group (89.2%), followed by the septostomy group (80.9%), compared with the control group (69.0%) (P = 0.006). A secondary analysis demonstrated that patients with both CAS and septostomy presented the highest rates of delivery prior to 34 weeks (100%) and 32 weeks (68.2%). CONCLUSIONS: CAS and septostomy following laser surgery for TTTS are independently associated with higher rates of preterm delivery. The presence of these two findings in the same patient enhances the risk of prematurity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial.

PURPOSE: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual's limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. METHODS: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. RESULTS: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. CONCLUSIONS: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations.

The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.

Arg206Cys substitution in DNASE1L3 causes a defect in DNASE1L3 protein secretion that confers risk of systemic lupus erythematosus.

OBJECTIVES: To determine if the polymorphism encoding the Arg206Cys substitution in DNASE1L3 explains the association of the DNASE1L3/PXK gene locus with systemic lupus erythematosus (SLE) and to examine the effect of the Arg206Cys sequence change on DNASE1L3 protein function. METHODS: Conditional analysis for rs35677470 was performed on cases and controls with European ancestry from the SLE Immunochip study, and genotype and haplotype frequencies were compared. DNASE1L3 protein levels were measured in cells and supernatants of HEK293 cells and monocyte-derived dendritic cells expressing recombinant and endogenous 206Arg and 206Cys protein variants. RESULTS: Conditional analysis on rs35677470 eliminated the SLE risk association signal for lead single-nucleotide polymorphisms (SNPs) rs180977001 and rs73081554, which are found to tag the same risk haplotype as rs35677470. The modest effect sizes of the SLE risk genotypes (heterozygous risk OR=1.14 and homozygous risk allele OR=1.68) suggest some DNASE1L3 endonuclease enzyme function is retained. An SLE protective signal in PXK (lead SNP rs11130643) remained following conditioning on rs35677470. The DNASE1L3 206Cys risk variant maintained enzymatic activity, but secretion of the artificial and endogenous DNASE1L3 206Cys protein was substantially reduced. CONCLUSIONS: SLE risk association in the DNASE1L3 locus is dependent on the missense SNP rs35677470, which confers a reduction in DNASE1L3 protein secretion but does not eliminate its DNase enzyme function.

Modeling of a Symmetric Five-Bar Displacement Amplification Compliant Mechanism for Energy Harvesting.

This paper presents an analytical model to determine a closed form mathematical representation for the output displacement of a displacement amplification compliant mechanism used for energy harvesting. A symmetric five-bar compliant mechanism with right-circular and corner-filleted flexure hinges was mathematically modeled and its displacement was determined using the Castigliano energy theorem. The stresses within the flexure joints, the weakest points in the mechanism body, were calculated. The mathematical model expresses both the displacement amplification and the stresses as functions of the design parameters and the load caused by the harvester. The developed model can be used to optimize the mechanism dimensions for maximum harvested power, while minimizing its structural stresses. The mechanism was also modeled numerically using finite element methods; both the analytical and numerical models were verified experimentally. The mathematical model of the mechanism was integrated with a model representing a piezoelectric energy harvester to calculate the open-circuit voltage. As a proof of concept, experiments were performed using an unimorph piezoelectric cantilever at low-frequency (less than 1 Hz) harmonic excitation inputs. The measured open-circuit voltage was found to be in agreement with that calculated using the proposed model, when integrated with the model representing the piezoelectric beam. The power generated by the piezoelectric harvester, equipped with the proposed displacement amplification mechanism, was more than a hundred times that without amplification.

Algorithm of FBG Spectrum Distortion Correction for Optical Spectra Analyzers with CCD Elements.

Nonlinear spectrum distortions are caused by the peculiarities of the operation of charge-coupled device elements (CCD), in which the signal exposition time (Time of INTegration-TINT) is one of the significant parameters. A change of TINT on a CCD leads to a nonlinear distortion of the resulting spectrum. A nonlinear distortion of the spectrum, in turn, leads to errors in determining the central wavelength of fiber Bragg gratings (FBGs) and spectrally sensitive sensors, which, in general, negatively affects the accuracy of the measuring systems. This paper proposes an algorithm for correcting the nonlinear distortions of the spectrum obtained on a spectrum analyzer using CCD as a receiver. It is shown that preliminary calibration of the optical spectrum analyzer with subsequent mathematical processing of the signal makes it possible to make corrections in the resulting spectrum, thereby leveling the errors caused by measurements at different TINT.

Occupational Inhalation Exposures to Nanoparticles at Six Singapore Printing Centers.

Laser printers emit high levels of nanoparticles (PM0.1) during operation. Although it is well established that toners contain multiple engineered nanomaterials (ENMs), little is known about inhalation exposures to these nanoparticles and work practices in printing centers. In this report, we present a comprehensive inhalation exposure assessment of indoor microenvironments at six commercial printing centers in Singapore, the first such assessment outside of the United States, using real-time personal and stationary monitors, time-integrated instrumentation, and multiple analytical methods. Extensive presence of ENMs, including titanium dioxide, iron oxide, and silica, was detected in toners and in airborne particles collected from all six centers studied. We document high transient exposures to emitted nanoparticles (peaks of ∼500 000 particles/cm3, lung-deposited surface area of up to 220 µm2/cm3, and PM0.1 up to 16 µg/m3) with complex PM0.1 chemistry that included 40-60 wt % organic carbon, 10-15 wt % elemental carbon, and 14 wt % trace elements. We also record 271.6-474.9 pmol/mg of Environmental Protection Agency-priority polycyclic aromatic hydrocarbons. These findings highlight the potentially high occupational inhalation exposures to nanoparticles with complex compositions resulting from widespread usage of nano-enabled toners in the printing industry, as well as inadequate ENM-specific exposure control measures in these settings.

Response of Practicing Chiropractors during the Early Phase of the COVID-19 Pandemic: A Descriptive Report.

OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic has strained all levels of healthcare and it is not known how chiropractic practitioners have responded to this crisis. The purpose of this report is to describe responses by a sample of chiropractors during the early stages of the COVID-19 pandemic. METHODS: We used a qualitative-constructivist design to understand chiropractic practice during the COVID-19 pandemic, as described by the participants. A sample of chiropractic practitioners (doctors of chiropractic, chiropractors) from various international locations were invited to participate. Each described the public health response to COVID-19 in their location and the actions that they took in their chiropractic practices from April 20 through May 4, 2020. A summary report was created from their responses and common themes were identified. RESULTS: Eighteen chiropractic practitioners representing 17 locations and 11 countries participated. A variety of practice environments were represented in this sample, including, solo practice, mobile practice, private hospital, US Veterans Administration health care, worksite health center, and group practice. They reported that they recognized and abided by changing governmental regulations. They observed their patients experience increased stress and mental health concerns resulting from the pandemic. They adopted innovative strategies, such as telehealth, to do outreach, communicate with, and provide care for patients. They abided by national and World Health Organization recommendations and they adopted creative strategies to maintain connectivity with patients through a people-centered, integrated, and collaborative approach. CONCLUSION: Although the chiropractors in this sample practiced in different cities and countries, their compliance with local regulations, concern for staff and patient safety, and people-centered responses were consistent. This sample covers all 7 World Federation of Chiropractic regions (ie, African, Asian, Eastern Mediterranean, European, Latin American, North American, and Pacific) and provides insights into measures taken by chiropractors during the early stages of the COVID-19 pandemic. This information may assist the chiropractic profession as it prepares for different scenarios as new evidence about this disease evolves.

Clinical efficacy of intrauterine cephapirin benzathine administration on clearance of uterine bacteria and subclinical endometritis in postpartum buffaloes.

This study examined the effect of single IU administration of cephapirin on clinical recovery, clearance of uterine bacteria and reproductive performance of postpartum buffaloes with subclinical endometritis (SCE). Buffaloes (n = 86) at 35 days postpartum (DPP) with >10% polymorphonuclear (PMN) cells in endometrial cytosmears were designated as positive (SCEP, n = 29), and buffaloes with ≤10% PMN cell were designated as negative (SCEN, n = 57) for SCE. Out of 29 positive buffaloes, 15 were administered a single intrauterine dose of cephapirin benzathine on 40 DPP (SCEP-CB), while the remaining 14 animals were kept as untreated control (SCEP-C). All animals were observed regularly for oestrous signs and were again subjected to cytobrush sampling on the first postpartum (FPP) oestrus. Buffaloes positive for SCE at 35 DPP were later considered "recovered" if their PMN cells dropped to ≤5% on the FPP oestrus. Presence of Escherichia coli, Arcanobacterium pyogenes and Fusobacterium necrophorum in uterus was detected based upon PCR amplification of genes related to bacteria-specific virulence factors. A total of 66.7% of SCEP-CB group buffaloes recovered as compared to 28.6% in SCEP-C (χ2  = 4.21; p < 0.05). Rate of bacterial clearance did not differ between treated (38.5%) and untreated buffaloes (8.3%) (χ2  = 1.67; p > 0.05). The median days to first service did not differ significantly (p > 0.05) among the three groups, whereas cephapirin administration reduced (p < 0.05) the days open by 14 days in SCEP-CB compared to SCEP-C buffaloes. SCEP-CB buffaloes were as likely to conceive as SCEN, whereas SCEP-C had 0.28 hazard ratio for pregnancy. In conclusion, a single treatment with cephapirin benzathine at 40 DPP improved the reproductive performance of buffaloes with subclinical endometritis.

Effects of mouthrinses on discoloration of CAD-CAM manufactured restorative materials.

PURPOSE: To investigate the in vitro effect of four different mouthrinses on discoloration of popular CAD-CAM blocks. METHODS: 40 specimens were prepared and then were divided into five groups (n = 8) for each CAD-CAM block (Vitablocks Mark II, IPS e-max CAD, GC LRF, Enamic, Cerasmart). In total, four different mouthrinses for each group (Listerine Zero, Parodontax, Kloroben, Oral B Pro-Expert) and distilled water for the control group were used. The specimens were immersed in 20 ml solution for 2 minutes, twice a day for 21 days with a 12-hour interval. Color changes were measured with a digital spectrophotometer (Vita Easyshade) after 7, 14 and 21 days and specimens were prepared. For statistical analysis, color changes ( ΔE) were calculated and Kruskal Wallis and Wilcoxon tests were used. RESULTS: There was not a significant difference in ΔE1 and ΔE2 values (P> 0.005) while there was a significant one in ΔE3 (P= 0.001) after Bonferroni correction for CAD-CAM materials were carried out as it is independent of the mouthrinse. Listerine Zero brought about the most noticeable color change in all CAD-CAM materials except e.Max after 21 days. CLINICAL SIGNIFICANCE: Discoloration effect of the tested mouthrinses on various CAD-CAM materials was different depending on the usage period. However, these differences did not exceed the clinically perceptible values.