PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation.

We characterized the regulatory mechanisms and role in human myeloid cell survival and differentiation of PRPF40A, a splicing factor lacking a canonical RNA Binding Domain. Upon PRPF40A knockdown, HL-60 cells displayed increased cell death, decreased proliferation and slight differentiation phenotype with upregulation of immune activation genes. Suggestive of both redundant and specific functions, cell death but not proliferation was rescued by overexpression of its paralog PRPF40B. Transcriptomic analysis revealed the predominant role of PRPF40A as an activator of cassette exon inclusion of functionally relevant splicing events. Mechanistically, the exons exclusively upregulated by PRPF40A are flanked by short and GC-rich introns which tend to localize to nuclear speckles in the nucleus center. These PRPF40A regulatory features are shared with other splicing regulators such as SRRM2, SON, PCBP1/2, and to a lesser extent TRA2B and SRSF2, as a part of a functional network that regulates splicing partly via co-localization in the nucleus.

Aerobic Exercise Training Response in Preterm-Born Young Adults with Elevated Blood Pressure and Stage 1 Hypertension: A Randomized Clinical Trial.

Rationale: Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of [Formula: see text]o2 at peak exercise intensity ([Formula: see text]o2PEAK) and at the ventilatory anaerobic threshold ([Formula: see text]o2VAT), but little is known about their response to exercise training. Objectives: The primary objective was to determine whether the [Formula: see text]o2PEAK response to exercise training differed between preterm-born and term-born individuals; the secondary objective was to quantify group differences in [Formula: see text]o2VAT response. Methods: Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16 weeks of aerobic exercise training (n = 102) or a control group (n = 101). Cardiopulmonary exercise tests were conducted before and after the intervention to measure [Formula: see text]o2PEAK and the [Formula: see text]o2VAT. A prespecified subgroup analysis was conducted by fitting an interaction term for preterm and term birth histories and exercise group allocation. Measurements and Main Results: For term-born participants, [Formula: see text]o2PEAK increased by 3.1 ml/kg/min (95% confidence interval [CI], 1.7 to 4.4), and the [Formula: see text]o2VAT increased by 2.3 ml/kg/min (95% CI, 0.7 to 3.8) in the intervention group versus controls. For preterm-born participants, [Formula: see text]o2PEAK increased by 1.8 ml/kg/min (95% CI, -0.4 to 3.9), and the [Formula: see text]o2VAT increased by 4.6 ml/kg/min (95% CI, 2.1 to 7.0) in the intervention group versus controls. No significant interaction was observed with birth history for [Formula: see text]o2PEAK (P = 0.32) or the [Formula: see text]o2VAT (P = 0.12). Conclusions: The training intervention led to significant improvements in [Formula: see text]o2PEAK and [Formula: see text]o2VAT, with no evidence of a statistically different response based on birth history. Clinical trial registered with www.clinicaltrials.gov (NCT02723552).

When is it safe to return to driving after distal radius fracture fixation? A prospective study.

INTRODUCTION: After surgical fixation of distal radius fractures, many patients are keen to return to driving. There are however limited guidelines assisting surgeons. The aims of this study were to determine when patients could return to driving safely after distal radius fracture fixation and determine the clinical parameters (range of motion and grip strength) that patients needed to achieve before return to safe driving could be advised. MATERIALS AND METHODS: A prospective grant-funded clinical study was conducted. Patients above the age of 21 years who underwent surgical fixation with a volar plate, possessed a class 3 standard motorcar license, and were regular drivers were recruited in a single institution from 2017 to 2019. A hand surgeon and an occupational therapist who sees routine hand therapy cases, assessed the patients at regular intervals from 2 to 12-weeks post-surgery. Clinical parameters of pain, wrist range of motion and grip strength were measured. Patients underwent off and on-road driving assessments. RESULTS: A total of 26 patients were recruited, with 21 successfully completing the driving assessment. Median time post-surgery to passing the driving test was 6 and 8-weeks for off and on-road assessments respectively. Pain score was observed to decrease over time, with a significant decrease from week 2 to week 4. Range of motion improved over time, with maximal improvement between 2 to 4-weeks post-surgery. When compared with the unaffected wrist, the difference in pronation, supination and radial deviation in the affected hand was consistently no longer statistically significant 4 to 6-weeks post-surgery. CONCLUSION: Patients with isolated surgically treated distal radius fractures can be recommended for a driving assessment as early as 4-6 weeks post-surgery if pain control is adequate, and clinical parameters for pronation and supination are met.

Return to work following knee arthroplasty: a retrospective review in urban Asian population.

BACKGROUND: An increasing number of working adults undergo knee arthroplasty in Singapore. There is limited data concerning Southeast Asian patients returning to work (RTW) following knee replacement surgery. Our aim was to identify and study factors influencing patients RTW following total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA). METHODS: Patients who underwent TKA or UKA between August 2017 and March 2020 in our center were included in this study. Outcomes include RTW and duration prior to RTW. RESULTS: 441 patients underwent TKA (295 women, 146 men, mean age 67.3 years) and 69 underwent UKA (48 women, 21 men, mean age 61.1 years). Patients who underwent TKA returned to work earlier (mean 83.7 ± 27.1 days) compared to UKA (mean 94.4 ± 42.3 days). 90.0% of TKA patients RTW compared to 95.5% who underwent UKA. Of patients who RTW, 94.3% of the TKA group returned to employment of the same nature compared to 92.9% of UKA patients. Patients who RTW were of a younger age (p = 0.03), white collared workers (p = 0.04), and had independent preoperative ambulatory status (p < 0.01). CONCLUSION: Younger and independently ambulating patients may have better capacity for rehabilitation and RTW post arthroplasty surgery.

Post-surgery interventions for hip fracture: a systematic review of randomized controlled trials.

BACKGROUND: Interventions provided after hip fracture surgery have been shown to reduce mortality and improve functional outcomes. While some systematic studies have evaluated the efficacy of post-surgery interventions, there lacks a systematically rigorous examination of all the post-surgery interventions which allows healthcare providers to easily identify post-operative interventions most pertinent to patient's recovery. OBJECTIVES: We aim to provide an overview of the available evidence on post-surgery interventions provided in the acute, subacute and community settings to improve outcomes for patients with hip fractures. METHODS: We performed a systematic literature review guided by the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA). We included articles that were (1) randomized controlled trials (RCTs), (2) involved post-surgery interventions that were conducted in the acute, subacute or community settings and (3) conducted among older patients above 65 years old with any type of non-pathological hip fracture that was surgically treated, and who were able to walk without assistance prior to the fracture. We excluded (1) non-English language articles, (2) abstract-only publications, (3) articles with only surgical interventions, (4) articles with interventions that commenced pre-surgery or immediately upon completion of surgery or blood transfusion, (5) animal studies. Due to the large number of RCTs identified, we only included "good quality" RCTs with Jadad score ≥ 3 for data extraction and synthesis. RESULTS: Our literature search has identified 109 good quality RCTs on post-surgery interventions for patients with fragility hip fractures. Among the 109 RCTs, 63% of the identified RCTs (n = 69) were related to rehabilitation or medication/nutrition supplementation, with the remaining RCTs focusing on osteoporosis management, optimization of clinical management, prevention of venous thromboembolism, fall prevention, multidisciplinary approaches, discharge support, management of post-operative anemia as well as group learning and motivational interviewing. For the interventions conducted in inpatient and outpatient settings investigating medication/nutrition supplementation, all reported improvement in outcomes (ranging from reduced postoperative complications, reduced length of hospital stay, improved functional recovery, reduced mortality rate, improved bone mineral density and reduced falls), except for a study investigating anabolic steroids. RCTs involving post-discharge osteoporosis care management generally reported improved osteoporosis management except for a RCT investigating multidisciplinary post-fracture clinic led by geriatrician with physiotherapist and occupational therapist. The trials investigating group learning and motivational interviewing also reported positive outcome respectively. The other interventions yielded mixed results. The interventions in this review had minor or no side effects reported. CONCLUSIONS: The identified RCTs regarding post-surgery interventions were heterogeneous in terms of type of interventions, settings and outcome measures. Combining interventions across inpatient and outpatient settings may be able to achieve better outcomes such as improved physical function recovery and improved nutritional status recovery. For example, nutritional supplementation could be made available for patients who have undergone hip fracture surgery in the inpatient settings, followed by post-discharge outpatient osteoporosis care management. The findings from this review can aid in clinical practice by allowing formulation of thematic program with combination of interventions as part of bundled care to improve outcome for patients who have undergone hip fracture surgery.

Mortality rates for hip fracture patients managed surgically and conservatively in a dedicated unit in Singapore.

INTRODUCTION: At our hospital, an unusually high proportion of patients and families opted for conservative management of hip fractures. This study aimed to compare the mortality rates of patients with hip fractures treated conservatively to that of operatively managed patients in a dedicated hip fracture unit. MATERIALS AND METHODS: Retrospective analysis was done for patients who were treated for hip fractures between January 2015 and October 2017 in a Hip Fracture Unit at a tertiary hospital. Patients were managed non-operatively or surgically after discussion with the multi-disciplinary team. RESULTS: 233 patients were treated conservatively and 781 underwent operative management for hip fractures. Patients managed non-operatively had a higher inpatient, 30-day and 1-year mortality rates. Inpatient mortality was 6.01% for conservatively managed compared to 0% for operative management. 30-day mortality for conservatively managed patients was 8.58% as compared to 0% for operatively managed patients, and 1-year mortality was 33.05% as opposed to 8.96%. There was an association seen with the type of management of hip fractures and that of inpatient death (p = 0.000), death in 30 days (p = 0.000) and death in 1 year (p = 0.000). The type of management was a predictive factor in 1-year mortality (p = 0.000). The average number of co-morbidities in conservatively managed patients was 5.2 compared to surgically managed patients of 4.0. Conservatively managed hip patients had a higher prevalence of stroke, chronic kidney disease and ischemic heart disease. Complications during hospital stay were comparable for both groups. The mean length of hospital stay was similar for both groups. CONCLUSION: Surgical intervention for hip fractures is associated with lower inpatient, 30-day and 1-year mortality rates. However, patient co-morbidities and pre-morbid conditions should also be considered. LEVEL OF EVIDENCE: IV.

Medial patellofemoral ligament reconstruction with and without trochleoplasty for patients with patella instability-correlation of trochlear dysplasia and patient outcome, classification and outcome measure in the past decade-a systematic review.

PURPOSE: The primary aim of the study is to compare the patient outcome in medial patellofemoral ligament reconstruction (MPFLR) or MPFLR concurrent with trochleoplasty (MPFLR + TP) and correlate it with the degree of trochlear dysplasia (TD). The secondary aim is to review TD classification, outcome measure, chronological and geographical trend of such studies in the past decade. METHODS: A systemic review of the literature in the past decade on studies of patients with patella instability and underwent either a MPFLR or MPFLR + TP. The degree of TD with the patient outcome was correlated and compared between the 2 groups. The TD classification, outcome measures, chronological and geographical trends of these studies were documented. RESULTS: There is no statistical difference in the overall improvement in the compared outcome scores between the 2 groups. However, the MPFLR studies reported a total of 16 re-dislocation in contrast to none in the MPFLR + TP studies. The 24 selected studies in the current review utilized different TD classification as well as outcome measures. A more homogeneous subgroup of 12 studies utilized Dejour classification as well as Kujala score that enabled comparison and showed no significant difference in outcome. The highest number of MPFLR publications was in 2019 and was from North and South Americas, Asia and Europe. The MPFLR + TP studies were from Europe during 2013 to 2017. CONCLUSION: Though there is an overall improvement in post-operative outcomes scores with no statistical significance between MPFLR and MPFLR + TP, the documented re-dislocations in the MPFLR studies suggested an undetermined zone where the choice of procedure could result in a different outcome. The current review did not show correlation between the degree of TD with the patient outcome to provide a clear indication for either procedure according to the degree of TD. The diverse TD classifications and varied outcome measures indicated the need for standardization and consistency in documentation to guide the treating clinician in the choice of procedure. MPFLR was more commonly performed and studied than MPFLR + TP in the past decade.

Household environmental microbiota influences early-life eczema development.

Exposure to a diverse microbial environment during pregnancy and early postnatal period is important in determining predisposition towards allergy. However, the effect of environmental microbiota exposure during preconception, pregnancy and postnatal life on development of allergy in the child has not been investigated so far. In the S-PRESTO (Singapore PREconception Study of long Term maternal and child Outcomes) cohort, we collected house dust during all three critical window periods and analysed microbial composition using 16S rRNA gene sequencing. At 6 and 18 months, the child was assessed for eczema by clinicians. In the eczema group, household environmental microbiota was characterized by presence of human-associated bacteria Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium at all time points, suggesting their possible contributions to regulating host immunity and increasing the susceptibility to eczema. In the home environment of the control group, putative protective effect of an environmental microbe Planomicrobium (Planococcaceae family) was observed to be significantly higher than that in the eczema group. Network correlation analysis demonstrated inverse relationships between beneficial Planomicrobium and human-associated bacteria (Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium). Exposure to natural environmental microbiota may be beneficial to modulate shed human-associated microbiota in an indoor environment.

Human PRPF40B regulates hundreds of alternative splicing targets and represses a hypoxia expression signature.

Altered splicing contributes to the pathogenesis of human blood disorders including myelodysplastic syndromes (MDS) and leukemias. Here we characterize the transcriptomic regulation of PRPF40B, which is a splicing factor mutated in a small fraction of MDS patients. We generated a full PRPF40B knockout (KO) in the K562 cell line by CRISPR/Cas9 technology and rescued its levels by transient overexpression of wild-type (WT), P383L or P540S MDS alleles. Using RNA sequencing, we identified hundreds of differentially expressed genes and alternative splicing (AS) events in the KO that are rescued by WT PRPF40B, with a majority also rescued by MDS alleles, pointing to mild effects of these mutations. Among the PRPF40B-regulated AS events, we found a net increase in exon inclusion in the KO, suggesting that this splicing factor primarily acts as a repressor. PRPF40B-regulated splicing events are likely cotranscriptional, affecting exons with A-rich downstream intronic motifs and weak splice sites especially for 5' splice sites, consistent with its PRP40 yeast ortholog being part of the U1 small nuclear ribonucleoprotein. Loss of PRPF40B in K562 induces a KLF1 transcriptional signature, with genes involved in iron metabolism and mainly hypoxia, including related pathways like cholesterol biosynthesis and Akt/MAPK signaling. A cancer database analysis revealed that PRPF40B is lowly expressed in acute myeloid leukemia, whereas its paralog PRPF40A expression is high as opposed to solid tumors. Furthermore, these factors negatively or positively correlated with hypoxia regulator HIF1A, respectively. Our data suggest a PRPF40B role in repressing hypoxia in myeloid cells, and that its low expression might contribute to leukemogenesis.

Role of maternal tryptophan metabolism in allergic diseases in the offspring.

BACKGROUND: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. OBJECTIVE: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. RESULTS: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

Global differences in atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder, with a highly variable prevalence worldwide. Recent evidence, however, has shown an increase in prevalence in the Asia Pacific region. Nevertheless, most of the published literature has focused mainly on Western populations, and only few clinical trials have included subgroups of other ethnic populations. Reasons for the observed ethnic and geographical differences in AD are not well established. This calls into question the need for a better understanding of AD pathogenesis and inter-ethnic differences in clinical and immuno-phenotypes. These differences may reflect inherent variability in disease mechanisms between populations, which in turn may impact upon treatment responses such as biologics that are currently tailored mainly to a specific immuno-phenotype (T-helper type 2 dominant). In this article, we reviewed existing literature on the prevalence of AD globally, highlighting differences, if any, in the clinical and immuno-phenotypes of AD between different ethnicities. We discussed genetic and environmental factors that affect AD in different populations and therapeutic considerations. Our review highlights AD as a disease with ethnic-dependent clinical and immunological heterogeneity and calls for greater inclusion of ethnic diversity in future research in order to develop targeted treatments.

Left atrial strain predicts cardiovascular response to exercise in young adults with suboptimal blood pressure.

AIMS: To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest. METHODS: A total of 127 adults aged 18-40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure <120/80mm Hg (n = 59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views. RESULTS: Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response ( ß = .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure. CONCLUSION: Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.

A proposed safety angle for dual bundle MPFL reconstruction: an observational magnetic resonance imaging study.

INTRODUCTION: The anatomical dual bundle medial patellofemoral ligament (MPFL) reconstruction technique is one of the surgical techniques used to treat lateral patellar instability. This commonly involves the creation of two patella bone tunnels through which the limbs of the grafts are inserted. The surgical risks include patellar fracture and penetration of patellofemoral articular surface. Thus, an easily reproducible intra-operative guiding parameter is useful to reduce such complications. PURPOSE: The aim of this study is to demarcate a safe working zone in the axial plane for the patella tunnels. METHODS: In this pilot study, we projected patella bone tunnels on the MRI knee images of 201 male patients with intact MPFLs. Two tunnel projections, superior and inferior, are made from the medial to the lateral sides of the patella. The projection of each superior and inferior tunnel is subdivided into three different angles in the axial plane. The tunnel length, thickness of the bone anterior to each tunnel and safety angle are measured. The safety angle refers to the angle between the longitudinal axis of each tunnel and the horizontal plane of the patella. RESULTS: Our current study population consisted of 201 male patients (104 Wiberg type 1, 97 Wiberg type 2, no type 3 or 4). For the superior tunnels, the tunnel lengths are 14.8 mm, 24.3 mm and 27.2 mm. The respective safety angles are 24.9 degrees, 24.5 degrees and 8.8 degrees. The thickness of the bone anterior to the tunnels are 5.9 mm, 2.5 mm and 6.2 mm. For the inferior tunnels, the tunnel lengths are 18.4 mm, 21.9 mm and 34.9 mm. The respective safety angles are 23.5 degrees, 22.5 degrees and 8.5 degrees. The thickness of the bone anterior to the respective tunnels are 5.9 mm, 3.1 mm and 6.0 mm. CONCLUSION: The proposed safety angle of 8.8 degree for the superior tunnel, and 8.5 degrees for the inferior tunnel is a potentially useful intra-operative guide for the surgeon and can potentially reduce the risks of fracture and articular cartilage injury in patellae with Wiberg 1 and 2 morphologies. LEVEL OF EVIDENCE: Level II, retrospective study.

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life.

Formation of the human heart involves complex biological signals, interactions, specification of myocardial progenitor cells, and heart tube looping. To facilitate survival in the hypoxemic intrauterine environment, the fetus possesses structural, physiological, and functional cardiovascular adaptations that are fundamentally different from the neonate. At birth, upon separation from the placental circulation, the neonatal cardiovascular system takes over responsibility of vital processes for survival. The transition from the fetal to neonatal circulation is considered to be a period of intricate physiological, anatomical, and biochemical changes in the cardiovascular system. With a successful cardiopulmonary transition to the extrauterine environment, the fetal shunts are functionally modified or eliminated, enabling independent life. Investigations using medical imaging tools such as ultrasound and magnetic resonance imaging have helped to define normal and abnormal patterns of cardiac remodeling both in utero and ex utero. This has not only allowed for a better understanding of how congenital cardiac malformations alter the hemodynamic transition to the extrauterine environment but also how other more common complications during pregnancy including intrauterine growth restriction, preeclampsia, and preterm delivery adversely affect offspring cardiac remodeling during this early transitional period. This review article describes key cardiac progenitors involved in embryonic heart development; the cellular, physiological, and anatomical changes during the transition from fetal to neonatal circulation; as well as the unique impact that different pregnancy complications have on cardiac remodeling.

Higher doses of topical tranexamic acid safely improves immediate functional outcomes and reduces transfusion requirement in total knee arthroplasty.

BACKGROUND: Topical administration of tranexamic acid (TXA) in patients undergoing total knee arthroplasty (TKA) is increasingly popular as it avoids the risks related with systemic absorption of the medication. Previous studies have established the efficacy of TXA in TKA, however here are limited direct comparison studies available and the dosing regimens vary. Hence, there is no consensus on an optimal dose. Our objective is to compare blood loss, transfusion requirement and immediate post-operative function between high (2 g) and low (1 g) dose tranexamic acid in patients undergoing TKA. METHODS: This is a retrospective cohort study of 104 patients undergoing total knee arthroplasty in a single institution under a single surgeon. In total, 61 and 43 patients receiving 1 g and 2 g of topical TXA respectively. Blood loss as estimated from the difference in haemoglobin (Hb) and haematocrit (HCT) levels post-surgery and number of blood transfusions required were compared between groups. Immediate post-operative function and complications were also measured. RESULTS: Patient characteristics were mostly similar between groups. The transfusion requirements were higher in 1 g group compared to the 2 g group (0.11 vs 0.00, p = 0.034). The mean post op day 1 (POD1) range of motion higher in the 1 g group vs 2 g group (72.1 vs 63.7, p = 0.035). The 2 g group had a lower POD1 pain score compared to the 1 g group (4.02 vs 5.43, p < 0.01). There was no statistically significant difference in complications that were related to the administration of TXA between the two groups. CONCLUSION: Higher dose of topical TXA is safe, helps improve immediate post-operative functional outcomes and reduces transfusion requirements.

Trial of exercise to prevent HypeRtension in young adults (TEPHRA) a randomized controlled trial: study protocol.

BACKGROUND: Hypertension prevalence in young adults has increased and is associated with increased incidence of cerebrovascular and cardiovascular events in middle age. However, there is significant debate regards how to effectively manage young adult hypertension with recommendation to target lifestyle intervention. Surprisingly, no trials have investigated whether lifestyle advice developed for blood pressure control in older adults is effective in these younger populations. METHODS/DESIGN: TEPHRA is an open label, parallel arm, randomised controlled trial in young adults with high normal and elevated blood pressure. The study will compare a supervised physical activity intervention consisting of 16 weeks structured exercise, physical activity self-monitoring and motivational coaching with a control group receiving usual care/minimal intervention. Two hundred young adults aged 18-35 years, including a subgroup of preterm born participants will be recruited through open recruitment and direct invitation. Participants will be randomised in a ratio of 1:1 to either the exercise intervention group or control group. Primary outcome will be ambulatory blood pressure monitoring at 16 weeks with measure of sustained effect at 12 months. Study measures include multimodal cardiovascular assessments; peripheral vascular measures, blood sampling, microvascular assessment, echocardiography, objective physical activity monitoring and a subgroup will complete multi-organ magnetic resonance imaging. DISCUSSION: The results of this trial will deliver a novel, randomised control trial that reports the effect of physical activity intervention on blood pressure integrated with detailed cardiovascular phenotyping in young adults. The results will support the development of future research and expand the evidence-based management of blood pressure in young adult populations. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02723552 , registered on 30 March, 2016.

Evaluating the Impact of the Healthy Beginnings System of Care Model on Pediatric Emergency Department Utilization.

OBJECTIVE: The aim of this study was to evaluate whether enrollment in the Healthy Beginnings System of Care (SOC) model is associated with a decrease in emergency department (ED) visits among children aged 6 months to 5.5 years. METHODS: A retrospective, longitudinal study of ED utilization was conducted among children enrolled in the Healthy Beginnings SOC model between February 2011 and May 2013. Using medical records obtained from a children's hospital in Atlanta, the rate of ED visits per quarter was examined as the main outcome. A multilevel, multivariate Poisson model, with family- and child-level random effects, compared ED utilization rates before and after enrollment. Adjusted rate ratios and 95% confidence intervals were calculated after controlling for sociodemographic confounders. RESULTS: The effect of SOC enrollment on the rate of ED visits differed by income level of the primary parent. The rate of ED visits after enrollment was not significantly different than the rate of ED visits before enrollment for children whose primary parent had an annual income of less than $5000 (P = 0.298), $20,000 to $29,999 (P = 0.199), or $30,000 or more (P = 0.117). However, for the children whose primary parent's annual income was $5000 to $19,999, the rate of ED visits after enrollment was significantly higher than the rate of ED visits before enrollment (adjusted rate ratio, 1.48; 95% confidence interval, 1.17-1.87). CONCLUSIONS: Enrollment in the SOC model does not appear to decrease the rate of ED visits among enrolled children. Additional strategies, such as education sessions on ED utilization, are needed to reduce the rate of ED utilization among SOC-enrolled children.

Vital Signs: Alcohol-Exposed Pregnancies--United States, 2011-2013.

BACKGROUND: Alcohol is a teratogen.* Prenatal alcohol exposure is associated with a range of adverse reproductive outcomes and can cause fetal alcohol spectrum disorders (FASDs) characterized by lifelong physical, behavioral, and intellectual disabilities. FASDs are completely preventable if a woman does not drink alcohol while pregnant. METHODS: CDC analyzed data from the 2011-2013 National Survey of Family Growth to generate U.S. prevalence estimates of risk for an alcohol-exposed pregnancy for 4,303 nonpregnant, nonsterile women aged 15-44 years, by selected demographic and behavioral factors. A woman was considered at risk for an alcohol-exposed pregnancy during the past month if she had sex with a male, drank any alcohol, and did not (and her partner did not with her) use contraception in the past month; was not sterile; and had a partner (or partners) not known to be sterile. RESULTS: The weighted prevalence of alcohol-exposed pregnancy risk among U.S. women aged 15-44 years was 7.3%. During a 1-month period, approximately 3.3 million women in the United States were at risk for an alcohol-exposed pregnancy. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Alcohol use in pregnancy is associated with low birthweight, preterm birth, birth defects, and developmental disabilities. Women of reproductive age should be informed of the risks of alcohol use during pregnancy, and contraception should be recommended, as appropriate, for women who do not want to become pregnant. Women wanting a pregnancy should be advised to stop drinking at the same time contraception is discontinued. Health care providers should advise women not to drink at all if they are pregnant or there is any chance they might be pregnant. Alcohol misuse screening and behavioral counseling (also known as alcohol screening and brief intervention) is recommended for all adults in primary care, including reproductive-aged and pregnant women, as an evidenced-based approach to reducing alcohol consumption among persons who consume alcohol in excess of the recommended guidelines.

One-dimensional fossil-like γ-Fe2O3@carbon nanostructure: preparation, structural characterization and application as adsorbent for fast and selective recovery of gold ions from aqueous solution.

One-dimensional (1D) magnetic nanostructures with high thermal stability have important industrial applications, but their fabrication remains a big challenge. Herein we demonstrate a scalable approach for the preparation of stable 1D γ-Fe2O3@carbon, which is also applicable for other metal oxide-core and carbon-shell nanostructures, such as 1D TiO2@carbon. One-dimensional ferric oxyhydroxide (α-FeO(OH)) was initially prepared by a hydrothermal method, followed by carbon coating through hydrothermal treatment of the resulting metal oxide in glucose solution. After calcination in N2 gas at 500 °C and subsequent exposure to air, the initial carbon-coated 1D α-Fe2O3 was converted to 1D γ-Fe2O3@carbon, which was very stable without any observed changes even after 1.5 years of storage under ambient conditions. The materials were then used as adsorbents and found to be highly selective towards Au (III) adsorption, of which the maximum adsorption capacity is about 600 mg Au/g sorbent (1132 mg Au/g carbon). The spent sorbent containing Au after adsorption can be readily collected by applying a magnetic field due to the presence of the magnetic core, and the adsorbed Au particles are subsequently recovered after the combustion and dissolution of the sorbent. This work demonstrates not only a facile approach to the fabrication of robust 1D magnetic materials with a stable carbon shell, but also a possible cyanide-free process for the fast and selective recovery of gold from electronic waste and industrial water.