Short term e-bicycle riding results in favorable cardiometabolic shifts in moderately active adults.

PURPOSE: Electric bikes (EB) are a form of active transportation with demonstrated health benefits. The purpose of this study was to determine the influence of riding an EB for one week on indices of cardiometabolic health in middle-aged adults. METHODS: Adults (n = 22; age = 57.1 ± 11.3 year; BMI = 27.7 ± 4.9) participated in a 2 week study. During Week 1, participants were instructed to continue regular activities. Starting Week 2 participants were provided an EB to ride at least 3 days for a minimum of 30 min·day-1. Physical activity (PA) and glucose were measured continuously. Body composition, blood lipids, glucose, insulin, hemoglobin A1c (HbA1c), plasma endothelin-1 (ET-1), and carotid-femoral pulse wave velocity (cf-PWV) were measured on days 1 and 14.Data and Statistical analyses or Statistics. Each participant served as their own control. Paired t-tests compared dependent variables between week 1 (without EB) and week 2 (with EB). RESULTS: When provided an EB for one week, moderate to vigorous PA increased by 6-9 min·day-1 (P < 0.05) and sedentary time decreased by ~ 77 min·day-1 (P < 0.05). Data from 24 h continuous glucose monitoring showed the percentage of time in healthy range (70-120 mg·dl-1 glucose) increased (P < 0.05) from week 1 to week 2. Compared to day 1, cf-PWV was lower at day 14 (P < 0.05) following one week of riding an EB. CONCLUSION: Moderately-active, middleaged adults showed improved continuous glucose regulation and lower central arterial stiffness following one week of riding an EB.

KOMPUTE: imputing summary statistics of missing phenotypes in high-throughput model organism data.

Motivation: The International Mouse Phenotyping Consortium (IMPC) is striving to build a comprehensive functional catalog of mammalian protein-coding genes by systematically producing and phenotyping gene-knockout mice for almost every protein-coding gene in the mouse genome and by testing associations between gene loss-of-function and phenotype. To date, the IMPC has identified over 90 000 gene-phenotype associations, but many phenotypes have not yet been measured for each gene, resulting in largely incomplete data; ∼75.6% of association summary statistics are still missing in the latest IMPC summary statistics dataset (IMPC release version 16). Results: To overcome these challenges, we propose KOMPUTE, a novel method for imputing missing summary statistics in the IMPC dataset. Using conditional distribution properties of multivariate normal, KOMPUTE estimates the association Z-scores of unmeasured phenotypes for a particular gene as a conditional expectation given the Z-scores of measured phenotypes. Our evaluation of the method using simulated and real-world datasets demonstrates its superiority over the singular value decomposition matrix completion method in various scenarios. Availability and implementation: An R package for KOMPUTE is publicly available at https://github.com/statsleelab/kompute, along with usage examples and results for different phenotype domains at https://statsleelab.github.io/komputeExamples.

Biological and JAK inhibitor therapy outcomes for severe psoriasis in trisomy 21.

Little is known about biological outcomes for severe psoriasis in trisomy 21 (T21). Our aim was to review outcomes of patients with T21 and severe psoriasis treated with biologic or Janus kinase inhibitors (JAKi). Information on demographics, co-morbidities, and therapeutic responses was retrospectively collated. Twenty-one patients were identified (mean age 24.7 years). Ninety percent (18/20) of TNFα inhibitor trials failed. Almost two-thirds (7/11) of patients achieved an adequate response with ustekinumab. All three patients treated with tofacitinib achieved an adequate response following at least three biologic failures. The mean number of biologic/JAKi therapies received was 2.1 with overall survival of 36%. Eighty-one percent (17/21) of patients required conversion from their index biologic treatment due to failure. In patients with T21 and severe psoriasis, failure of TNFα inhibition is common and ustekinumab therapy should be considered as first-line therapy. The role of JAKi is emerging.

Outcomes of Uterine Rupture in the Setting of the Unscarred Compared With the Scarred Uterus.

Uterine rupture is a rare obstetric complication that is associated with maternal and neonatal morbidity and mortality. The aim of this study was to examine uterine rupture and its outcomes in the setting of the unscarred compared with the scarred uterus. A retrospective observational cohort study was performed examining all cases of uterine rupture in three tertiary care hospitals in Dublin, Ireland, over a 20-year period. The primary outcome was perinatal mortality rate with uterine rupture, which was 11.02% (95% CI 6.5-17.3). There was no significant difference in perinatal mortality between cases of scarred and unscarred uterine rupture. Unscarred uterine rupture was associated with higher maternal morbidity , defined as major obstetric hemorrhage or hysterectomy.

Lens Epithelial Explants Treated with Vitreous Humor Undergo Alterations in Chromatin Landscape with Concurrent Activation of Genes Associated with Fiber Cell Differentiation and Innate Immune Response.

Lens epithelial explants are comprised of lens epithelial cells cultured in vitro on their native basement membrane, the lens capsule. Biologists have used lens epithelial explants to study many different cellular processes including lens fiber cell differentiation. In these studies, fiber differentiation is typically measured by cellular elongation and the expression of a few proteins characteristically expressed by lens fiber cells in situ. Chromatin and RNA was collected from lens epithelial explants cultured in either un-supplemented media or media containing 50% bovine vitreous humor for one or five days. Chromatin for ATAC-sequencing and RNA for RNA-sequencing was prepared from explants to assess regions of accessible chromatin and to quantitatively measure gene expression, respectively. Vitreous humor increased chromatin accessibility in promoter regions of genes associated with fiber differentiation and, surprisingly, an immune response, and this was associated with increased transcript levels for these genes. In contrast, vitreous had little effect on the accessibility of the genes highly expressed in the lens epithelium despite dramatic reductions in their mRNA transcripts. An unbiased analysis of differentially accessible regions revealed an enrichment of cis-regulatory motifs for RUNX, SOX and TEAD transcription factors that may drive differential gene expression in response to vitreous.

Approach to Handling Atypical Field Blood Transfusion Scenarios.

Special Operations Forces (SOF) medical personnel have been at the forefront of administering blood products in the austere field medicine environment. These far-forward medical providers regularly treat patients and deliver blood transfusions in some of the world's most extreme environments with minimal resources. A multitude of questions have been raised on this topic based on the unique experiences of senior providers in this field. In this paper, we analyze the available literature and present the recommendations of several experts in transfusion medicine for managing atypical field transfusion scenarios.

Drug use in pregnancy in Ireland's capital city: A decade of trends and outcomes.

OBJECTIVE: The aim of this study was to present contemporary trends in opiate use disorder (OUD) and substance use in pregnancy in Ireland, with associated obstetric outcomes, over the last ten years. STUDY DESIGN: This retrospective observational cohort study was conducted at an Irish tertiary maternity unit. All women with OUD or substance use in pregnancy delivered under this service between 2010 and 2019 were included. Drug-exposure was self-reported. Data was collected by combining electronic and hand-held patient records. Trends and outcomes were analysed by year of delivery. Approval for the study was granted by the institution's clinical governance committee. RESULTS: Of the 82,669 women delivered, 525 had OUD or substance use in pregnancy (1 in every 160 women booking). 11.6% were homeless, 20.0% were in full-time employment and 91.0% smoked tobacco in pregnancy. 66.3% had a history of psychiatric disorders. Over the ten years, there was a significant reduction in women delivered with OUD or substance use in pregnancy (0.8 % to 0.4 %, RR 0.55, 95 % CI 0.36-0.85), significant reduction in the proportion of women on Opioid-Substitute-Treatment (OST, RR 0.66 95 % CI 0.51-0.87) and an increase in mean maternal age (30.7to32.0 years). Rates of cocaine and cannabis consumption increased (20.6 %, RR 3.8, 95 % CI 1.57-9.44: 24.0 %, RR 3.7, 95 % CI 1.58-8.86 respectively). The maternal mortality rate was 380.9:100,000 births. The perinatal mortality rate was 15.6:1000 births. The preterm birth rate was 17.9 %, with a mean birth weight of 2832 g. The rate of NICU admission was 52.0 % and the mean length of stay was 22.4 days. Amongst the smaller OUD population, the rate of NICU admission for Neonatal Abstinence Syndrome (NAS) and treatment for NAS increased over the study timeframe (36.0 %, RR 2.97, 95 % CI 1.86-4.75: 28.5 %, RR 2.92, 95 % CI 1.70-5.0 respectively). CONCLUSIONS: The obstetric population attending an Irish antenatal service with opiate use disorder or substance exposure is reducing in size with older patients, less opioid substitute therapy and increasing cocaine and cannabis use. These women have high rates of maternal and perinatal morbidity and mortality. Specialist antenatal addiction services, coordinated by the drug-liaison midwife, are critical in adapting care to respond to this dynamic and vulnerable patient cohort.

Assessing Patterns of Anti-Social and Risky Behaviour in the Millennium Cohort Study-What Are the Roles of SES (Socio-Economic Status), Cognitive Ability and Personality?

Data from the Millennium Cohort Study (UK) were examined to assess the correlates of anti-social and risky behaviour among adolescents. Over 10,000 seventeen-year-olds were asked about their participation in anti-social or risky behaviours. For SES (socio-economic status), the survey's details around household income, and the educational attainment and occupational status of respondents' parents were used. A latent measure was extracted from assessments of cognitive ability. Personality measures-the 'Big Five'-were included, as was a composite measure of hyperactivity. SES and cognitive ability were very weakly associated with anti-social and risky behaviour, while personality measures, and hyperactivity were more strongly linked. Hyperactivity, Agreeableness and Extraversion were the most important measures linked to a measure of anti-social and risky activities (ASRA) and its subscales.

Non-diabetic fetal macrosomia: outcomes of elective delivery versus expectant management.

BACKGROUND: Macrosomia in the absence of diabetes can be associated with increased neonatal and maternal morbidity. Management is usually undertaken on a case-by-case basis. AIMS: In order to inform local practice, this study aimed to evaluate the outcomes of the management of non-diabetic macrosomia in an Irish tertiary center. METHODS: A retrospective observational study was performed on all women with estimated fetal weight over 4000 g after 37 weeks' gestation. Maternal demographics and obstetric and neonatal outcomes were recorded using the hospital information system. Women with diabetes, previous caesarean section, non-cephalic presentation, or any other complicating condition were excluded. Women were divided into two groups: 1. Active management: Elective delivery for macrosomia-between 38 + 0 and 40 + 6 weeks' gestation 2. Expectant management: with induction of labour offered after 41 weeks' gestation RESULTS: There were 397 women included, 188 with active and 209 with expectant management. There was no difference in adverse neonatal outcomes, major maternal morbidity, or mode of delivery, after exclusion of pre-labor caesarean section. Women with expectant management were more likely to go into spontaneous labor (46.9 vs 1.6%, p < 0.001) and to have a favorable cervix at the onset of induction of labor if nulliparous (86.1 vs 70.0%, p = 0.021), but have higher rates of episiotomy (28.6 vs 18.2%, p = 0.021). With active management, nulliparas with an unfavorable cervix had increased risk of anal sphincter injury (6.5 vs 0.0%, p = 0.007) and postpartum hemorrhage (59.0 vs 35.5%, p = 0.003). CONCLUSIONS: Overall, there was no difference in major maternal or neonatal outcomes between management options for fetal macrosomia. However, inducing nulliparas with an unfavorable cervix for non-diabetic macrosomia was associated with obstetric anal sphincter injury and postpartum hemorrhage.

Midwives' personal and professional attitudes towards women's delivery choices, interventions and neonatal care.

OBJECTIVES: Caesarean section (CS) rates in middle- and high-income countries are rising partly due to maternal request. This study aimed to explore the personal and professional attitudes of midwives and nurses towards women's delivery choices, interventions and neonatal care. METHODS: Midwifery and nursing staff at the Coombe hospital were asked to complete a questionnaire concerning decisions for elective CS and neonatal care. The midwives' responses were divided into multiparous and nulliparous according to their own parity. RESULTS: Multiparae and nulliparae did not differ on their personal preferences for their own baby. Only 3% wanted an elective CS in a normal, healthy pregnancy but this increased to 80.2% when there was a breech presentation and 42% if the estimated fetal weight was >4.5 kg. These numbers and trends were very close to the midwives' professional recommendations under the same circumstances. The lower threshold for full resuscitation and ICU care was at 23 and 24 weeks gestation for both personal and professional recommendations. In the case of severely premature babies or babies with a poor prognosis, 54% stated that the approach to neonatal care was correct. CONCLUSIONS: Overall, midwives' professional views reflected what they would want for themselves and their babies. Only 3% recommended an elective CS in a normal, healthy pregnancy making it unlikely that midwives' attitudes are driving the rise in CS rates in Ireland.

Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms.

Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where basal serum tryptase (BST) levels >20 ng/mL are a minor criterion for diagnosis. Although clonal myeloid neoplasms are rare, the common cause for elevated BST levels is the genetic trait hereditary α-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from overexpression of replicated TPSAB1 loci encoding canonical α-tryptase protein owing to coinheritance of a linked overactive promoter element. Modeling BST levels based on TPSAB1 replication number, we generate new individualized clinical reference values for the upper limit of normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (eg, >100 ng/mL), which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within normal limits for certain individuals with HαT.

NSABP FC-6: Surgical conversion rate in colorectal cancer patients with unresectable, KRAS wild-type liver metastases receiving mFOLFOX7 plus cetuximab.

PURPOSE: This study sought to determine the R0 resection rate in KRAS wild-type (WT), liver-only metastatic colorectal cancer (CRC) patients initially identified as having unresectable disease who were treated with FOLFOX7 plus cetuximab. Exploratory molecular analyses were undertaken before and after treatment. METHODS: Twenty patients were enrolled. None had prior adjuvant chemotherapy. Cetuximab was added to a FOLFOX7 backbone and administered at 500 mg/m2 every 14 days with dose reductions to 400 and 300 mg/m2 in the event of toxicity. In the absence of toxicity, dose-escalations to 600, 700, and 800 mg/m2 were allowed. The mean dose of cetuximab (mg/m2 /week) throughout the study was 289 mg/m2 . Paired samples were collected for correlative studies, where feasible. RESULTS: We assessed the conversion rates from unresectable to resectable in hepatic-only, KRAS exon 2 WT mCRC. Seventeen of 20 patients undergoing chemotherapy were considered resectable by imaging criteria; R0 resection was achieved in 15/20 patients. Molecular profiling revealed heterogeneity between patients at the gene-expression, pathway signaling, and immune-profile levels. CONCLUSIONS: Although 15/20 (75%) converted to R0 resection, by 2 years, 10/15 R0 resections had recurred. Therefore, chemotherapy plus cetuximab is of limited long-term benefit in this setting. ctDNA analysis may guide additional therapy including immunotherapy.

Weighted Baseball Training Affects Arm Speed Without Increasing Elbow and Shoulder Joint Kinetics.

Long-term training effects of weighted ball throwing programs have been well documented. However, the mechanisms that facilitate these effects are poorly understood. The purpose of this study is to investigate within-session effects of throwing overload and underload baseballs to provide mechanistic evidence for weighted baseball training methods. Twenty-six collegiate- and professional-level baseball pitchers aged 20-30 years (mean age 23.5 [2.7] y) participated in a biomechanical evaluation while pitching a series of leather weighted baseballs. A 1-way repeated-measures analysis of variance was used to evaluate the intrasubject effect of ball weight on a total of 15 kinematic, kinetic, and performance parameters. Ball weight significantly affected pitch velocity, maximum elbow flexion, maximum pelvis rotation velocity, maximum shoulder internal rotation velocity, maximum elbow extension velocity, and anterior trunk tilt at ball release. None of the measured arm joint kinetics were significantly affected by ball weight. Training with 3- to 7-ounce (85- to 198-g) baseballs can be used to work on increasing pitching velocity without increasing throwing arm joint kinetics.

Hyperbaric effects on cold stored whole blood following a military dive mission profile.

BACKGROUND: Whole blood (WB) is carried by special operations forces as part of a remote damage control resuscitation strategy. The effects of an underwater mission on the quality and coagulation profile of WB were simulated by exposure to hyperbaric pressures in a chamber. METHODS: WB units collected in CPDA-1 were exposed to three different combinations of hyperbaric pressure and duration of exposure: Group A 153.52 kPa (15.24 msw; 1.52 atm) for 4 h; n = 9, Group B 506.63 kPa (50.29 msw; 5.00 atm) for 1 h; n = 9, Group C 153.52 kPa (15.24 msw; 1.52 atm) for 1 h; n = 7. The following parameters were measured on each unit: prothrombin time/international normalized ratio, activated partial thromboplastin time, thromboelastography and concentration determinations of platelets, lactate, fibrinogen, and lactate dehydrogenase. Each sample underwent baseline, prepressurization, immediate postpressurization, and 6 h postpressurization laboratory testing. RESULTS: Six hours following hyperbaric exposure, the lactate concentration in group C was higher than prepressurization measurement and the platelet concentration in Group A was lower than prepressurization measurement. There were no changes in any of the other analyzed biochemical, coagulation and thromboelastogram parameters following exposure to hyperbaric stress. DISCUSSION: These data suggest that pressurization of WB up to 5 atm did not impact parameters tested. Changes observed in lactate and platelet count need further study, as well as complementary testing of red blood cell integrity. Further investigation of the hyperbaric extremes is necessary to determine if there is a damage inducing pressure to which WB should not be exposed.

Neural-Fly enables rapid learning for agile flight in strong winds.

Executing safe and precise flight maneuvers in dynamic high-speed winds is important for the ongoing commoditization of uninhabited aerial vehicles (UAVs). However, because the relationship between various wind conditions and its effect on aircraft maneuverability is not well understood, it is challenging to design effective robot controllers using traditional control design methods. We present Neural-Fly, a learning-based approach that allows rapid online adaptation by incorporating pretrained representations through deep learning. Neural-Fly builds on two key observations that aerodynamics in different wind conditions share a common representation and that the wind-specific part lies in a low-dimensional space. To that end, Neural-Fly uses a proposed learning algorithm, domain adversarially invariant meta-learning (DAIML), to learn the shared representation, only using 12 minutes of flight data. With the learned representation as a basis, Neural-Fly then uses a composite adaptation law to update a set of linear coefficients for mixing the basis elements. When evaluated under challenging wind conditions generated with the Caltech Real Weather Wind Tunnel, with wind speeds up to 43.6 kilometers/hour (12.1 meters/second), Neural-Fly achieves precise flight control with substantially smaller tracking error than stateof-the-art nonlinear and adaptive controllers. In addition to strong empirical performance, the exponential stability of Neural-Fly results in robustness guarantees. Last, our control design extrapolates to unseen wind conditions, is shown to be effective for outdoor flights with only onboard sensors, and can transfer across drones with minimal performance degradation.

Resolving the genetics of human tryptases: implications for health, disease, and clinical use as a biomarker.

PURPOSE OF REVIEW: To discuss our evolving understanding of the genetic variation in human tryptases and recent advances in associated clinical phenotypes. RECENT FINDINGS: Serum tryptase levels have long been used as biomarkers in clinical practice to diagnose mast cell-associated disorders and mast cell-mediated reactions but the contribution of specific secreted isoforms of human tryptases and their role(s) in health and disease has only recently begun to be illuminated. It is now recognized that hereditary alpha-tryptasemia (HαT) is a common genetic trait and the commonest cause for elevated basal serum tryptase (BST), where it can both contribute to mast cell-associated phenotypes, and potentially confound their correct diagnosis. Expression of different tryptase isoforms is now recognized to be associated with specific clinical phenotypes including clonal and nonclonal mast cell-associated disorders as well as certain asthma endotypes. These disparate impacts on clinical disorders may result from differences in enzymatic activities of mature α-tryptases and ß-tryptases, and the unique substrate profile and stability of heterotetrameric mature α/ß-tryptases recently described to naturally occur. SUMMARY: Variable copy number and isoform expression of tryptases differentially impact diseases and reactions associated with mast cells in humans. Recent advances in understanding of genetics governing BST levels have refined our understanding and the clinical use of this biomarker. In the future, incorporation of tryptase genotyping will likely be integral to the work-up and trial design of patients with phenotypes impacted by mast cells ranging from asthma to mastocytosis.

Case report and literature review of management of preterm prelabour rupture of membranes before fetal viability.

Preterm prelabour rupture of membranes (PPROM) complicates up to 3% of pregnancy and is responsible for one third of preterm deliveries. PPROM at extremely preterm gestations (<24 weeks) affects 0.4% of pregnancies and is associated with low neonatal survival rates, high rate of neonatal complications in survivors, and carries major risk of maternal morbidity and mortality. We present a rare case of pregnancy complicated by PPROM at 14 weeks which resulted in a term delivery and a good neonatal outcome.

Visually guided chick ocular length and structural thickness variations assessed by swept-source optical coherence tomography.

Chicks are an excellent model for studying myopia. To study the change of the ocular structures in chicks, ultrasound is mostly used. However, it suffers from limited spatial resolution. In this study, we investigated the axial length (AL) and the thickness of different ocular structures in chicks' eye undergoing visually induced changes using a swept-source optical coherence tomography (SS-OCT) system in vivo. Two groups of chicks wore a translucent plastic goggle (n = 6) over the right eye to induce form-deprivation myopia. Following 12 days of form deprivation, goggles were removed in one group of chicks (n = 3), and they were allowed to experience 5 days of unrestricted vision (recovery). Goggles remained in place for a total of 17 days for the remaining 3 chicks. A separate group of 3 chicks were untreated and served as normal control. Ocular dimensions were measured in control, myopic, and recovered eyes using an SS-OCT system. We found myopic chick eyes had significantly thicker AL, lens thickness (LT), anterior chamber depth (ACD), and vitreous chamber depth (VCD), but significantly thinner retina thickness (RT) and choroid thickness (ChT) compared to the control eyes. Following 5 days of recovery, the cornea thickness (CT), retina pigment epithelium thickness (RPET), and ChT were significantly thicker, while the ACD and LT became significantly thinner compared to that of myopic eyes. SS-OCT can serve as a promising tool to provide measurements of the entire ocular structures, for evaluating the change of thickness and depth of different ocular structures in chicks in vivo. The change of AL in the myopic and recovered chick eyes can be attributed to the thickness alterations of different ocular structures. Altogether, this work demonstrated the feasibility of SS-OCT in chick myopic research and exhibited new insights into the changes of ocular structures in chicks experiencing myopia after unrestricted vision recovery.