Activity-based profiling of cullin-RING E3 networks by conformation-specific probes.

The cullin-RING ubiquitin ligase (CRL) network comprises over 300 unique complexes that switch from inactive to activated conformations upon site-specific cullin modification by the ubiquitin-like protein NEDD8. Assessing cellular repertoires of activated CRL complexes is critical for understanding eukaryotic regulation. However, probes surveying networks controlled by site-specific ubiquitin-like protein modifications are lacking. We developed a synthetic antibody recognizing the active conformation of NEDD8-linked cullins. Implementing the probe to profile cellular networks of activated CUL1-, CUL2-, CUL3- and CUL4-containing E3s revealed the complexes responding to stimuli. Profiling several cell types showed their baseline neddylated CRL repertoires vary, and prime efficiency of targeted protein degradation. Our probe also unveiled differential rewiring of CRL networks across distinct primary cell activation pathways. Thus, conformation-specific probes can permit nonenzymatic activity-based profiling across a system of numerous multiprotein complexes, which in the case of neddylated CRLs reveals widespread regulation and could facilitate the development of degrader drugs.

The microprotein Nrs1 rewires the G1/S transcriptional machinery during nitrogen limitation in budding yeast.

Commitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NRS1 for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon TORC1 inhibition, and cell cycle-regulated with a peak at Start. NRS1 interacted genetically with SWI4 and SWI6, which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity, and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogen conditions.

Estimation of the proximal temperature rise of an excited upconversion particle by detecting the wavefront of emission.

Monitoring the temperature distribution within a local environment at the micro and nanoscale is vital as many processes are solely thermal. Various thermometric techniques have been explored in the community, and out of these, fluorescent nano/micro particle-based mechanisms are accepted widely (fluorescence intensity ratio (FIR) techniques, where the ratio of populations in two consecutive energy levels is compared with Boltzmann distribution). We describe a new technique to account for the temperature rise near an illuminated upconverting particle (UCP) using wavefront imaging, which is more sensitive than the conventional thermometric techniques on the microscale. We rely on a thermo-optical phase microscopic technique by reconstructing the wavefront of emission from an upconverting particle using a Shack-Hartmann wavefront sensor. The wavefront maps the local phase distribution, which is an indicator of the surroundings' optical parameters, particularly the suspended medium's temperature-induced refractive index in the presence of convection currents. We describe how these extracted phase values can provide information about the optical heating due to the particle and hence its local environment along the direction of the emission. Our findings demonstrate the detection of a minimum temperature rise of 0.23 K, while the FIR methods indicate a minimum of 0.3 K rise. This technique is used to study the temperature increase in the backscattered direction for an upconverting particle illuminated on pump resonance. We also estimate the Soret coefficient for an upconverting particle optically trapped on pump resonance and experiencing anisotropic heating across the body.

Provider opinions on effectiveness of physical therapy as treatment for glenohumeral arthritis.

BACKGROUND: Physical therapy (PT) is a described first-line treatment option for glenohumeral arthritis, but its efficacy for treating this spectrum of disease is not well understood. The purpose of this study is to evaluate the opinions of expert providers-orthopedic surgeons and physical therapists-regarding the utility of PT in treating glenohumeral arthritis in different stages of radiographic severity. Our goal is to identify areas of interprofessional majority agreement as well as areas without agreement that warrant further investigation. METHODS: A 35-question survey was created and distributed via email to members of the American Shoulder and Elbow Surgeons and the American Society of Shoulder and Elbow Therapists, collecting information on demographics, professional experience, and the perceived benefit of PT for patients with different stages of glenohumeral arthritis based on radiographic severity. Survey responses were analyzed for inter-professional differences in distribution of answer choices as well as for majority agreement statements. Items with >50% agreement from a professional group were considered statements of majority agreement. RESULTS: One hundred and ninety surgeons and 39 physical therapists completed the survey. Surgeons and therapists demonstrated different distribution of answer choices in 25 of the 29 nondemographic related questions (86%). Surgeons and therapists reached the same majority statement in 8 items (28%) and reached disagreeing majority statements in 4 items (14%). They agreed on the benefits of PT for mild arthritis, the benefits of corticosteroid injections, the frequency of strengthening exercises, and that PT failure should not be required for surgical approval in patients with severe arthritis. They disagreed on the whether PT exacerbates symptoms in patients with moderate arthritis, and whether preoperative PT influences postoperative outcomes. CONCLUSION: Both surgeons and therapists agreed that PT may be less beneficial for patients with more advanced radiographic arthritis and that PT failure should not be required for insurance approval for surgical intervention in patients with severe glenohumeral arthritis. Further research is needed to determine the efficacy of PT for patients with moderate arthritis as well as the utility of preoperative PT for improving postoperative outcomes.

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Efficacy and outcome of indocyanine green-based intraoperative cholangiography using near-infrared fluorescence imaging: A prospective study.

INTRODUCTION: The most dreaded complication during laparoscopic cholecystectomy still remains to be injury to the common bile duct. The primary cause for bile duct injury during LC is misinterpretation of the biliary anatomy. Intra-operative cholangiography was introduced as a means of reducing the chances of biliary injury, done using Fluoroscopic imaging or Near-infrared fluorescence imaging method. NIRF is one of the most popular imaging methods in biomedical sciences. Indocyanine Green is sterile and water soluble which completely binds to albumin and is excreted in bile. PATIENTS AND METHODS: This prospective study was conducted among 70 patients between July 2020 and December 2021. Subjects were administered 5mg of ICG dye pre-operatively and procedure performed using Karl Storz HD image S1 system with a D-light P light source for NIRF imaging. RESULTS: The average duration of surgery was 58.10 minutes. After calot's dissection, the CBD was visualized in 88.71 % patients, with a mean time to visualization at 26.33 minutes. The cystic duct was visualized in 87.3% cases with a mean time of visualization of 32.10 minutes. The hepatic duct was visualized in 28.57% and the hepatic duct-CBD confluence was visualized in 34.28% patients. CONCLUSION: Near infrared imaging based intra-operative cholangiography, using Indocyanine Green dye, during Lap. Cholecystectomy is an easy, useful and inexpensive method of visualizing the biliary ductal anatomy.

Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.

PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.

Intrinsic and strain dependent ultralow thermal conductivity in novel AuX (X = Cu, Ag) monolayers for outstanding thermoelectric applications.

A large power factor and ultralow lattice thermal conductivity in 2D-monolayers of AuX (X = Cu and Ag) are achieved via first principles calculations. Low phonon frequency, small Debye temperature and high Gruneisen parameter limit the intrinsic thermal conductivity of both the studied materials. An ultra-low lattice thermal conductivity of 0.13 (0.30) W m-1 K-1 and 0.66 (1.59) W m-1 K-1 is obtained for unstrained AuCu and AuAg monolayers, respectively, at 700 (300) K, which further reduces to 0.04 (0.09) and 0.26 (0.63) W m-1 K-1 at 6% biaxial tensile strain. Such values of thermal conductivity are lower than the critical thermal conductivity for the state-of-art thermoelectric materials (kl < 2 W m-1 K-1). The peak values of ZT for unstrained monolayers are 2.20 and 1.40, which enhances to 3.61 and 2.91 at 6% strain for AuCu and AuAg monolayers, respectively. Interestingly pudding-mold band textures are found to be responsible for this unusual thermoelectric behaviour. The stability concerns (chemical/dynamic/mechanical) of these monolayers are ensured to stimulate experimental determinations for novel synthesis and possible applications.

A novel technique for frame-based MR-guided laser ablation in an infant.

Hypothalamic hamartomata (HH) not only are usually associated with drug-resistant epilepsy but can also cause precocious puberty and developmental delay. Gelastic seizures are the most common type of seizures. Magnetic resonance image (MRI)-guided laser interstitial thermal therapy (LiTT) is a technique whereby a laser fibre is stereotactically implanted into a target lesion and heat is used to ablate whilst tissue temperature is monitored using MRI thermography. MRI-guided LiTT has proven to be an effective and safe method to treat HH. To use the LiTT system, highly accurate stereotactic fibre implantation is required. This can be achieved by the use of frame-based or frameless neuronavigation techniques. However, these techniques generally involve rigid head immobilisation using cranial pin fixation. Patients need sufficient skull thickness to safely secure the pins and sufficient skull rigidity to prevent deformation. Hence, most of the clinical reports on the use of LiTT for children describe patients aged 2 years or older. We report a novel and practical technique of using a paste cast helmet to securely place a stereotactic frame in a 5-month-old infant with HH and drug-resistant epilepsy that allowed the successful application of MRI-guided LiTT.

Intra-Articular Platelet Rich Plasma vs Corticosteroid Injections for Sacroiliac Joint Pain: A Double-Blinded, Randomized Clinical Trial.

OBJECTIVE: Using stringent inclusion criteria, a double-blinded study protocol, and fluoroscopically guided injections, we compare intra-articular sacroiliac joint platelet-rich plasma injections with intra-articular steroids. DESIGN: Double-blind, randomized controlled trial. SETTING: Two large university-based interdisciplinary spine centers. SUBJECTS: A total of 26 patients with a positive diagnostic block (>80% relief). METHODS: Subjects who had a positive diagnostic block were randomized to undergo either a fluoroscopically guided intra-articular injection of steroid or a platelet-rich plasma injection. Follow-up was at 1 month, 3 months, and 6 months. Outcomes included level of pain, as indicated on a 0- to 100-mm numeric pain rating scale, and functional disability score, obtained via the Oswestry Disability Index (ODI). RESULTS: At 1, 3, and 6 months, both groups improved; however, subjects who received steroid injections reported lower pain scores than did subjects who received platelet-rich plasma. Using categorical data, we observed significantly more responders (defined as pain scores that improved by 50% or more from baseline) at 1 and 3 months in the group who received steroids than in the group who received platelet-rich plasma. CONCLUSION: Although both groups showed improvements in pain and function, the steroid group had significantly greater response and significantly more responders than did the platelet-rich plasma group.

Electronic Structure-, Phonon Spectrum-, and Effective Mass- Related Thermoelectric Properties of PdXSn (X = Zr, Hf) Half Heuslers.

We hereby discuss the thermoelectric properties of PdXSn(X = Zr, Hf) half Heuslers in relation to lattice thermal conductivity probed under effective mass (hole/electrons) calculations and deformation potential theory. In addition, we report the structural, electronic, mechanical, and lattice dynamics of these materials as well. Both alloys are indirect band gap semiconductors with a gap of 0.91 eV and 0.82 eV for PdZrSn and PdHfSn, respectively. Both half Heusler materials are mechanically and dynamically stable. The effective mass of electrons/holes is (0.13/1.23) for Zr-type and (0.12/1.12) for Hf-kind alloys, which is inversely proportional to the relaxation time and directly decides the electrical/thermal conductivity of these materials. At 300K, the magnitude of lattice thermal conductivity observed for PdZrSn is 15.16 W/mK and 9.53 W/mK for PdHfSn. The highest observed ZT value for PdZrSn and PdHfSn is 0.32 and 0.4, respectively.

Development of inclined plate honey moisture reduction system.

Honey is delicious, nutritious and has high medicinal value in comparison to other sweeteners. Honey is usually extracted from comb as immature product which results in high moisture which makes it more liable to be fermented by osmophilic yeasts. So, it needs to be processed for moisture reduction, to delay crystallization and to overcome the problem of fermentation. In the present investigation, a honey moisture reduction system was developed and tested to reduce the moisture content of honey to about 17%. The system consisted of a flat plate inclined at an angle. The plate was heated from the underside and honey for moisture reduction was re-circulated over it until desired moisture content was achieved. Experiments were conducted for honey moisture reduction at water temperature of 40-70 °C with plate inclinations of 30°-60° according to four level full factorial design of experiment. The results showed that the total reduction time required for reaching moisture content of about 17% varied with water temperature and angle of inclination. The moisture reduction time required for reaching a moisture content of 17 percent at 40 °C was about five times the time required at 70 °C. The energy cost of honey moisture content reduction from 21.5 to 17% was Rs. 4.7 to Rs. 12.5 per kg.

Childhood arterial ischemic stroke due to mineralizing angiopathy: an 18-year single-center experience.

Mineralizing angiopathy is a unique, age-specific stroke syndrome characterized by basal ganglia infarction and lenticulostriate calcification after minor head injury in early childhood. There is limited understanding of the pathophysiology, course, and clinical outcome of this syndrome. We describe the clinical and radiographical phenotype of a single-center, consecutively enrolled cohort of children with mineralizing angiopathy from January 2002 to January 2020 and provide a comparative analysis to previously published literature. Fourteen children were identified. Previously unreported findings include: stroke onset in eight children older than 18 months; presence of basal ganglia hemorrhage in four; multifocal basal ganglia infarcts in three; presence of additional non-basal ganglia calcifications in three; and presence of thrombophilia in one. Seven children had moderate-to-severe neurological deficits. There was no symptomatic stroke recurrence (mean follow-up 3y 7mo, SD 1y 7mo). Our expanded phenotype highlights distinct characteristics of mineralizing angiopathy in children and has the potential to inform future research. What this paper adds Children with mineralizing angiopathy are often misdiagnosed as having a limb fracture despite normal x-rays. A magnetic resonance imaging-only approach may miss this entity. Non-contrast computed tomography, in addition to MRI is recommended to identify calcifications in idiopathic arterial ischemic stroke. Most children have moderate-to-severe neurological sequela.

Telecritical Care Clinical and Operational Strategies in Response to COVID-19.

Background: The cororavirus disease 19 (COVID-19) pandemic has strained intensive care unit (ICU) material and human resources to global crisis levels. The risks of staffing challenges and clinician exposure are of significant concern. One resource, telecritical care (TCC), has the potential to optimize efficiency, maximize safety, and improve quality of care provided amid large-scale disruptions, but its role in pandemic situations is only loosely defined. Planning and Preparation Phase: We propose strategic initiatives by which TCC may act as a force multiplier for pandemic preparedness in response to COVID-19, utilizing a tiered approach for increasing surge capacity needs. The goals involved usage of TCC to augment ICU capacity, optimize safety, minimize personal protective equipment (PPE) use, improve efficiencies, and enhance knowledge of managing pandemic response. Implementation Phase: A phased approach utilizing TCC would involve implementing remote capabilities across the enterprise to accomplish the goals outlined. The hardware and software needed for initial expansion to cover 275 beds included $956,670 for mobile carts and $173,106 for home workstations. Team role deployment and bedside clinical care centering around TCC as critical care capacity expand beyond 275 beds. Surge capacity was not reached during early phases of the pandemic in the region, allowing refinement of TCC during subsequent pandemic phases. Conclusions: Leveraging TCC facilitated pandemic surge planning but required redefinition of typical ICU staffing models. The design was meant to workforce efficiencies, reduce PPE use, and minimize health care worker exposure risk, all while maintaining quality care standards through an intensivist-led model. As health care operations resumed and states reopened, TCC is being used to support shifts in volume and critical care personnel during the pandemic evolution. The lessons applied may help health care systems through variable phases of the pandemic.

Simultaneous Assessment of Intracellular and Extracellular pH Using Hyperpolarized [1-13C]Alanine Ethyl Ester.

Tissue pH is tightly regulated in vivo, being a sensitive physiological biomarker. Advent of dissolution dynamic nuclear polarization (DNP) and its translation to humans stimulated development of pH-sensitive agents. However, requirements of DNP probes such as biocompatibility, signal sensitivity, and spin-lattice relaxation time (T1) complicate in vivo translation of the agents. Here, we developed a 13C-labeled alanine derivative, [1-13C]-l-alanine ethyl ester, as a viable DNP probe whose chemical shift is sensitive to the physiological pH range, and demonstrated the feasibility in phantoms and rat livers in vivo. Alanine ethyl ester readily crosses cell membrane while simultaneously assessing extracellular and intracellular pH in vivo. Following cell transport, [1-13C]-l-alanine ethyl ester is instantaneously hydrolyzed to [1-13C]-l-alanine, and subsequently metabolized to [1-13C]lactate and [13C]bicarbonate. The pH-insensitive alanine resonance was used as a reference.

Vitamin D supplementation for sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a genetic chronic haemolytic and pro-inflammatory disorder. With increased catabolism and deficits in energy and nutrient intake, individuals with SCD suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. This is an update of a previous review. OBJECTIVES: To investigate the effects of vitamin D supplementation in children and adults with SCD and to compare different dose regimens. To determine the effects of vitamin D supplementation on general health (e.g. growth status and health-related quality of life), on musculoskeletal health (including bone mineral density, pain crises, bone fracture and muscle health), on respiratory health (including lung function, acute chest syndrome, acute exacerbation of asthma and respiratory infections) and the safety of vitamin D supplementation. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 March 2020. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews. Date of last search: 14 January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing oral administration of any form of vitamin D supplementation at any dose and for any duration to another type or dose of vitamin D or placebo or no supplementation in people with SCD, of all ages, gender, and phenotypes. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the risk of bias of the included studies. They used the GRADE guidelines to assess the quality of the evidence. MAIN RESULTS: Vitamin D versus placebo One double-blind RCT (n = 39) compared oral vitamin D3 (cholecalciferol) supplementation (20 participants) to placebo (19 participants) for six weeks. Only 25 participants completed the full six months of follow-up. The study had a high risk of bias due to incomplete outcome data, but a low risk of bias for randomisation, allocation concealment, blinding (of participants, personnel and outcome assessors) and selective outcome reporting; and an unclear risk of other biases. Vitamin D supplementation probably led to higher serum 25(OH)D levels at eight weeks, mean difference (MD) 29.79 (95% confidence interval (CI) 26.63 to 32.95); at 16 weeks, MD 12.67 (95% CI 10.43 to 14.90); and at 24 weeks, MD 15.52 (95% CI 13.50 to 17.54) (moderate-quality evidence). There was little or no difference in adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% CI 0.14 to 72.84) (low-quality evidence). Vitamin D supplementation probably caused fewer pain days compared to the placebo group at eight weeks, MD -10.00 (95% CI -16.47 to -3.53) (low-quality evidence), but probably led to a lower (worse) health-related quality of life score (change from baseline in physical functioning PedsQL scores); at both 16 weeks, MD -12.56 (95% CI -16.44 to -8.69) and 24 weeks, MD -12.59 (95% CI -17.43 to -7.76), although this may not be the case at eight weeks (low-quality evidence). Vitamin D supplementation regimens compared Two double-blind RCTs (83 participants) compared different regimens of vitamin D. One RCT (n = 62) compared oral vitamin D3 7000 IU/day to 4000 IU/day for 12 weeks, while the second RCT (n = 21) compared oral vitamin D3 100,000 IU/month to 12,000 IU/month for 24 months. Both RCTs had low risk of bias for blinding (of participants, personnel and outcome assessors) and incomplete outcome data, but the risk of selective outcome reporting bias was high. The bias from randomisation and allocation concealment was low in one study but not in the second. There was an unclear risk of other biases. When comparing oral vitamin D 100,000 IU/month to 12,000 IU/month, the higher dose may have resulted in higher serum 25(OH)D levels at one year, MD 16.40 (95% CI 12.59 to 20.21) and at two years, MD 18.96 (95% CI 15.20 to 22.72) (low-quality evidence). There was little or no difference in adverse events between doses (low-quality evidence). There were more episodes of acute chest syndrome in the high-dose group, at one year, MD 0.27 (95% CI 0.02 to 0.52) but there was little or no difference at two years, MD 0.09 (95% CI -0.04 to 0.22) (moderate-quality evidence). At one year and two years there was also little or no difference between the doses in the presence of pain (moderate-quality evidence) or forced expiratory volume in one second % predicted. However, the high-dose group had lower values for % predicted forced vital capacity at both one and two years, MD -7.20% predicted (95% CI -14.15 to -0.25) and MD -7.10% predicted (95% CI -14.03 to -0.17), respectively. There were little or no differences between dose regimens in the muscle health of either hand or the dominant hand. The study comparing oral vitamin D3 7000 IU/day to 4000 IU/day (21 participants) did not provide data for analysis, but median serum 25(OH)D levels were reported to be lower in the low-dose group at both six and 12 weeks. At 12 weeks the median serum parathyroid hormone level was lower in the high-dose group. AUTHORS' CONCLUSIONS: We included three RCTs of varying quality. We consider that the current evidence presented in this review is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation and dietary reference intakes for calcium and vitamin D. Well-designed RCTs of parallel design, are required to determine the effects and the safety of vitamin D supplementation as well as to assess the relative benefits of different doses in children and adults with SCD.

Probing carbohydrate metabolism using hyperpolarized 13 C-labeled molecules.

Glycolysis is a fundamental metabolic process in all organisms. Anomalies in glucose metabolism are linked to various pathological conditions. In particular, elevated aerobic glycolysis is a characteristic feature of rapidly growing cells. Glycolysis and the closely related pentose phosphate pathway can be monitored in real time by hyperpolarized 13 C-labeled metabolic substrates such as 13 C-enriched, deuterated D-glucose derivatives, [2-13 C]-D-fructose, [2-13 C] dihydroxyacetone, [1-13 C]-D-glycerate, [1-13 C]-D-glucono-δ-lactone and [1-13 C] pyruvate in healthy and diseased tissues. Elevated glycolysis in tumors (the Warburg effect) was also successfully imaged using hyperpolarized [U-13 C6 , U-2 H7 ]-D-glucose, while the size of the preexisting lactate pool can be measured by 13 C MRS and/or MRI with hyperpolarized [1-13 C]pyruvate. This review summarizes the application of various hyperpolarized 13 C-labeled metabolites to the real-time monitoring of glycolysis and related metabolic processes in normal and diseased tissues.

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population.

Risk factors for arterial ischemic stroke in children include vasculopathy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from databases held in Canada (Toronto), Germany (Kiel-Lübeck/Münster), and the UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age, 6 years) with a median follow-up of 35 months. Among these 894 patients, 160 (17.9%) had a recurrence between 1 day and 136 months after the first stroke (median, 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common [hazard ratio (HR) 2.5, 95% confidence interval (95% CI) 1.92-3.5] compared to the rate in children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95% CI: 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95% CI: 1.3-4.1), and the presence of more than one prothrombotic risk factor (HR 1.9; 95% CI: 1.12-3.2) were independently associated with an increased risk of recurrence. Recurrence rates calculated per 100 person-years were 10 (95% CI: 3-24) for antithrombin deficiency, 6 (95% CI: 4-9) for elevated lipoprotein (a), and 13 (95% CI: 7-20) for the presence of more than one prothrombotic risk factor. Identifying children at increased risk of a second stroke is important in order to intensify measures aimed at preventing such recurrences.

The Effectiveness of Autologous Platelet-Rich Plasma for Osteoarthritis of the Hip: A Retrospective Analysis.

BACKGROUND: Platelet-rich plasma (PRP) is a minimally invasive treatment option to reduce pain and promote tissue healing. At the time this study was performed, there was limited published literature analyzing outcomes for patients treated with PRP for hip osteoarthritis. METHODS: Thirty-six patients aged 49-85 (66.0 ± 12.1) years with chronic hip pain who met inclusion criteria underwent image-guided intra-articular hip PRP injection. Outcomes were measured at baseline, two weeks, three months, and up to six months using the visual analog scale (VAS) for pain and the Hip Disability and Osteoarthritis Outcome Score (HOOS). The proportion of responders, as defined by a ≥50% reduction in VAS pain score, was assessed at three and six months. RESULTS: At two weeks, there was a significant improvement (P < 0.05) of function in two HOOS subscales: Symptoms and Activities of Daily Living. There was a significant improvement in all HOOS categories at six months. A significant improvement in VAS was observed at six months (baseline VAS = 6.9 ± 0.7 &→ 4.3 ± 1.8, 95% confidence interval = 2.0 to 3.2, P < 0.05). Sixty-seven percent (24/36) of the patients reported a ≥50% improvement in pain at three months; 58% (21/36) reported a ≥50% improvement in pain at six months. Stratification by Kellgren-Lawrence grades revealed that 86% and 82% of the KL grades 1 and 2 were responders at six months, respectively. CONCLUSIONS: In patients with mild/moderate hip osteoarthritis, PRP may provide pain relief and functional improvement for up to six months.

Surface-enhanced spin current to charge current conversion efficiency in CH3NH3PbBr3-based devices.

Hybrid organic-inorganic perovskites have shown great promise for spintronic applications due to their large spin-orbit coupling induced by the Pb and halogen atoms. Particularly, the large observed surface-induced Rashba splitting in CH3NH3PbBr3 indicates efficient spin-current-to-charge-current (StC) conversion, which, however, has not been demonstrated yet. In this work, the StC conversion efficiency in ferromagnet/CH3NH3PbBr3-based devices is studied using the pulsed spin-pumping technique measured by the inverse spin Hall effect. We found that the StC conversion efficiency is anomalous in that it increases at small perovskite layer thickness. This indicates the existence of a surface-dominated StC mechanism such as the inverse Rashba-Edelstein effect. By inserting a thin LiF layer between the ferromagnet and the perovskite film, the StC conversion efficiency is greatly suppressed, validating the existence of a Rashba surface in the CH3NH3PbBr3 film.