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Despite medical treatment focused on addressing walking disability, many millions of people with neurological conditions, like cerebral palsy (CP), struggle to maintain independent mobility. Lower limb exoskeletons and exosuits may hold potential for augmenting walking ability. However, it remains unknown whether these wearable robots are safe and beneficial for use outside of highly controlled laboratory environments, the demonstration of which is necessary for clinical translation. Here, we show that a lightweight, portable, ankle exoskeleton with an adaptable one-size-works-for-all assistance controller can improve energy efficiency and walking speed for individuals with CP spanning a wide spectrum of lower limb impairment in a multi-terrain real-world environment. Tested on an outdoor walking route with level, sloped, and stair terrain, robotic assistance resulted in a 15-18% (p = 0.013-0.026) reduction in estimated energy cost and a 7-8% (p = 0.001-0.004) increase in average walking speed across "shorter" 6-minute and "longer" 20-minute walking durations relative to unassisted walking. This study provides evidence that wearable robots may soon improve mobility in neighborhood, school, and community settings for individuals with CP.
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Nitrous oxide is a widely used and well-established form of inhalation sedation in dentistry. Its properties have a wide margin of safety and allow for anxious, paediatric and adult patients to receive dental treatment with minimal impact upon discharge. Nitrous oxide has drawbacks, however, including its environmental impact and need for specialist equipment. Methoxyflurane is another drug which could prove to be an alternative to nitrous oxide. Methoxyflurane's use has proved popular within emergency medicine in Australia and New Zealand for its potent analgesic effects and recognition of its anxiolytic effect. As a result, its use in invasive outpatient procedures has now become popular. Unfortunately, there is very limited evidence of its use within dentistry as a form of inhalation sedation and analgesic. A wider evidence base should be established, as methoxyflurane could prove to be an effective and environmentally friendly alternative to nitrous oxide.
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Anestesia Dental , Anestésicos por Inhalación , Metoxiflurano , Óxido Nitroso , Humanos , Anestesia Dental/métodos , Anestésicos por Inhalación/administración & dosificación , Sedación Consciente/métodos , Isoflurano/administración & dosificación , Metoxiflurano/administración & dosificación , Metoxiflurano/uso terapéutico , Metoxiflurano/farmacología , Óxido Nitroso/administración & dosificaciónRESUMEN
Altered medial/lateral knee muscle co-contraction (measure by co-contraction indices, CCI) occurs during gait early after anterior cruciate ligament reconstruction (ACLR). Changes in peak medial compartment forces (pMCF) are also observed early after ACLR and are linked to the development of knee osteoarthritis. We do not know if imbalanced co-contraction is associated with these alterations in knee load. The purpose of this study was to evaluate the association between pMCF and the CCIs of medial/lateral knee muscle pairs during walking three months after ACLR. Bilateral knee gait mechanics and electromyography (EMG) data were collected from 44 participants 3 months following surgery. CCIs of six muscle pairs and medial-to-lateral (M:L) CCIs ratios were calculated during the weight acceptance interval. Bilateral pMCFs were calculated using a subject-based neuromusculoskeletal model. Based on interlimb pMCF symmetry, participants were divided into three groups: symmetric loaders, underloaders, and overloaders. A 2 × 3 (limb × group) ANOVA was used to compare CCIs between limbs in all groups. A partial Spearman's test was performed to examine the association between CCIs ratios and pMCF. The CCIs of the vastus lateralis-lateral gastrocnemius muscle pair was higher in the involved limb of underloaders (vs. the uninvolved limb and vs. the involved limb of symmetric loaders). The ratio of M:L CCIs was significantly lower (more lateral CCIs) in the involved limb, which was associated with lower pMCF. These results suggest that individuals early after ACLR who walk with higher CCIs of lateral knee musculature (vs. medial), have medial tibiofemoral underloading.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Lesiones del Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Articulación de la Rodilla/cirugía , Marcha/fisiología , Músculo EsqueléticoRESUMEN
Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%-5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.
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Escoliosis , Animales , Ratones , Humanos , Adolescente , Femenino , Masculino , Escoliosis/genética , Rotación , Columna Vertebral , Fenotipo , GenómicaRESUMEN
We have established hydrogen atom transfer (HAT) as the key player in a directed, photopromoted fluorination of pyridylic groups. The Lewis basic pyridyl nitrogen directs amine radical dication propagated HAT and Selectfluor fluorination of various ortho substituents in a highly regioselective manner with little to no side product formation. A variety of pyridines and quinolines were employed to showcase the directing capability of the nitrogen atom. Additionally, both experimental and computational data are provided that illuminate how this mechanism differs from and complements prior work in the area.
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Peptidyl arginine deiminase 6 (PADI6) is a maternal factor that is vital for early embryonic development. Deletion and mutations of its encoding gene in female mice or women lead to early embryonic developmental arrest, female infertility, maternal imprinting defects and hyperproliferation of the trophoblast. PADI6 is the fifth and least well-characterized member of the peptidyl arginine deiminases (PADIs), which catalyse the post-translational conversion of arginine to citrulline. It is less conserved than the other PADIs, and currently has no reported catalytic activity. While there are many suggested functions of PADI6 in the early mouse embryo, including in embryonic genome activation, cytoplasmic lattice formation, maternal mRNA and ribosome regulation, and organelle distribution, the molecular mechanisms of its function remain unknown. In this review, we discuss what is known about the function of PADI6 and highlight key outstanding questions that must be answered if we are to understand the crucial role it plays in early embryo development and female fertility. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.
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Desarrollo Embrionario , Fertilidad , Arginina Deiminasa Proteína-Tipo 6 , Animales , Femenino , Humanos , Ratones , Arginina/metabolismo , Arginina Deiminasa Proteína-Tipo 6/genética , Arginina Deiminasa Proteína-Tipo 6/metabolismo , Ribosomas/metabolismoRESUMEN
In this note, we explore a unique reactivity pattern that involves a rare radical-based C-C bond scission of epoxides followed by demethylenation. The reaction is accomplished by Selecfluor and its radical dication working in tandem; a mechanism supported by experiment and DFT calculations is proposed that involves the generation and identification of a key reactive intermediate. The reaction seems to be fairly general for 1,1-disubstituted epoxides.
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OBJECTIVE: Growth hormone insensitivity (GHI) encompasses growth restriction, normal/elevated growth hormone (GH), and low insulin-like growth factor I (IGF1). "Nonclassical" GHI is poorly characterized and is rarely caused by heterozygous dominant-negative (DN) variants located in the intracellular or transmembrane domains of the GH receptor (GHR). We sought to determine the molecular mechanisms underpinning the growth restriction in 2 GHI cases. METHODS AND DESIGN: A custom-made genetic investigative pipeline was exploited to identify the genetic cause of growth restriction in patients with GHI. Nanoluc binary technology (NanoBiT), in vitro splicing assays, western blotting, and flow cytometry, characterized the novel GHR variants. RESULTS: Novel heterozygous GHR variants were identified in 2 unrelated patients with GHI. In vitro splicing assays indicated both variants activated the same alternative splice acceptor site resulting in aberrant splicing and exclusion of 26 base pairs of GHR exon 9. The GHR variants produced truncated receptors and impaired GH-induced GHR signaling. NanoBiT complementation and flow cytometry showed increased cell surface expression of variant GHR homo/heterodimers compared to wild-type (WT) homodimers and increased recombinant human GH binding to variant GHR homo/heterodimers and GH binding protein (GHBP) cleaved from the variant GHRs. The findings demonstrated increased variant GHR dimers and GHBP with resultant GH sequestration. CONCLUSION: We identified and characterized 2 novel, naturally occurring truncated GHR gene variants. Intriguingly, these DN GHR variants act via the same cryptic splice acceptor site, highlighting impairing GH binding to excess GHBP as a potential therapeutic approach.
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Enanismo , Hormona de Crecimiento Humana , Humanos , Hormona del Crecimiento/genética , Receptores de Somatotropina/genética , Sitios de Empalme de ARN , Hormona de Crecimiento Humana/metabolismo , Enanismo/genética , Factor I del Crecimiento Similar a la Insulina/genéticaRESUMEN
Sphingosine 1-phosphate lyase (SGPL1) insufficiency (SPLIS) is a syndrome which presents with adrenal insufficiency, steroid-resistant nephrotic syndrome, hypothyroidism, neurological disease, and ichthyosis. Where a skin phenotype is reported, 94% had abnormalities such as ichthyosis, acanthosis, and hyperpigmentation. To elucidate the disease mechanism and the role SGPL1 plays in the skin barrier we established clustered regularly interspaced short palindromic repeats-Cas9 SGPL1 KO and a lentiviral-induced SGPL1 overexpression (OE) in telomerase reverse-transcriptase immortalised human keratinocytes (N/TERT-1) and thereafter organotypic skin equivalents. Loss of SGPL1 caused an accumulation of S1P, sphingosine, and ceramides, while its overexpression caused a reduction of these species. RNAseq analysis showed perturbations in sphingolipid pathway genes, particularly in SGPL1_KO, and our gene set enrichment analysis revealed polar opposite differential gene expression between SGPL1_KO and _OE in keratinocyte differentiation and Ca2+ signaling genesets. SGPL1_KO upregulated differentiation markers, while SGPL1_OE upregulated basal and proliferative markers. The advanced differentiation of SGPL1_KO was confirmed by 3D organotypic models that also presented with a thickened and retained stratum corneum and a breakdown of E-cadherin junctions. We conclude that SPLIS associated ichthyosis is a multifaceted disease caused possibly by sphingolipid imbalance and excessive S1P signaling, leading to increased differentiation and an imbalance of the lipid lamellae throughout the epidermis.
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Ictiosis , Esfingolípidos , Humanos , Calcio/metabolismo , Aldehído-Liasas/genética , Aldehído-Liasas/metabolismo , Lisofosfolípidos/metabolismo , Esfingosina/genética , Esfingosina/metabolismo , Ictiosis/genéticaRESUMEN
Testing for hepatitis C virus (HCV) is currently targeted towards those at high-risk in France. While universal screening was recently rejected, a growing body of research from other high-income countries suggests that HCV testing in emergency departments (ED) can be effective and cost-effective. In the absence of any studies on the effectiveness of HCV testing in ED attendees in France, this study aimed to perform an early economic evaluation of ED-based HCV testing. A Markov model was developed to simulate HCV testing in the ED versus no ED testing. The model captured costs from a French health service perspective, presented in 2020 euros, and outcomes, presented as quality-adjusted life years (QALYs), over a lifetime horizon. Incremental cost-effectiveness ratios (ICER) were calculated as costs per QALYs gained and compared to willingness-to-pay thresholds of 18,592 and 33,817 per QALY. Value of information analyses were also performed. ED testing for HCV was cost-effective at both thresholds when assuming ED prevalence of 1.1%, yielding an ICER of 3,800 per QALY. Testing remained cost-effective when the HCV prevalence amongst ED attendees remained higher than in the general population (0.3%). The maximum value of future research ranged from 10 to 79 million, depending on time horizons and willingness-to-pay thresholds. Our analysis suggests ED-based HCV testing may be cost-effective in France, although there is uncertainty due to the lack of empirical studies available. Further research is of high value, suggesting seroprevalence surveys and pilot studies in French ED settings are warranted.
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OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC. DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs. RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells. CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Carcinoma Corticosuprarrenal/genética , Aldehído-Liasas/genética , Aldehído-Liasas/metabolismo , Esfingolípidos , Neoplasias de la Corteza Suprarrenal/genéticaRESUMEN
Advanced health economic analysis techniques currently performed in Microsoft Excel, such as incorporating heterogeneity, time-dependent transitions and a value of information analysis, can be easily transferred to R. Often the outputs of survival analyses (such as Weibull regression models) will estimate the impacts of correlated patient characteristics on patient outcomes, and are utilised directly as inputs for health economic decision models. This tutorial provides a step-by-step guide of how to conduct such analyses with a Markov model developed in R, and offers a comparison with established analyses performed in Microsoft Excel. This is done through the conversion of a previously published Microsoft Excel case study of a hip replacement surgery cost-effectiveness model. We hope that this paper can act as a facilitator in switching decision models from Microsoft Excel to R for complex health economic analyses, providing open-access code and data, suitable for future adaptation.
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Modelos Económicos , Humanos , Análisis Costo-BeneficioRESUMEN
A health economic evaluation (HEE) is a comparative analysis of alternative courses of action in terms of both costs and consequences. A cost-effectiveness analysis is a type of HEE that compares an intervention to one or more alternatives by estimating how much it costs to gain an additional unit of health outcome. Cost-effectiveness analyses are commonly performed using Microsoft (MS) Excel. However, there is current interest in using other software that is better suited to more complex problems, methods, and data, as well as improved reproducibility and transparency. That is, it is increasingly important to be able to repeat an analysis of a particular data set and obtain the same results, and access the analysis and results in a clear and comprehensive openly available form. In this tutorial we provide a step-by-step guide on how to implement a mainstay model of HEE, namely a Markov model, in the statistical programming language R. The adoption of R for the purpose of cost-effectiveness analysis is highly dependent on the ability of the health economic modeller to understand, learn, and apply programming-type skills. R is likely to be less familiar than MS Excel for many modellers and so coding a cost-effectiveness model in R can be a large jump. We describe the technical details from the perspective of a MS Excel user to help bridge the gap between software and reduce the learning curve by providing for the first-time side-by-side comparisons of the Markov model example in MS Excel and R.
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Economía Médica , Programas Informáticos , Humanos , Análisis Costo-Beneficio , Reproducibilidad de los Resultados , Análisis de Costo-EfectividadRESUMEN
The clinical efficacy of robotic rehabilitation interventions hinges on appropriate neuromuscular recruitment from the patient. The first purpose of this study was to evaluate the use of supervised machine learning techniques to predict neuromuscular recruitment of the ankle plantar flexors during walking with ankle exoskeleton resistance in individuals with cerebral palsy (CP). The second goal of this study was to utilize the predictive models of plantar flexor recruitment in the design of a personalized biofeedback framework intended to improve (i.e., increase) user engagement when walking with resistance. First, we developed and trained multilayer perceptrons (MLPs), a type of artificial neural network (ANN), utilizing features extracted exclusively from the exoskeleton's onboard sensors, and demonstrated 85-87% accuracy, on average, in predicting muscle recruitment from electromyography measurements. Next, our participants completed a gait training session while receiving audio-visual biofeedback of their personalized real-time planar flexor recruitment predictions from the online MLP. We found that adding biofeedback to resistance elevated plantar flexor recruitment by 24 16% compared to resistance alone. This study highlights the potential for online machine learning frameworks to improve the effectiveness and delivery of robotic rehabilitation systems in clinical populations.
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BACKGROUND: Numerous studies have shown the effectiveness of testing for hepatitis B (HBV) and hepatitis C (HCV) in emergency departments (ED), due to the elevated prevalence amongst attendees. The aim of this study was to conduct a cost-effectiveness analysis of universal opt-out HBV and HCV testing in EDs based on 2 long-term studies of the real-world effectiveness of testing in 2 large ED's in the UK. METHODS: A Markov model was used to evaluate ED-based HBV and HCV testing versus no ED testing, in addition to current testing practice. The two EDs had a HBV HBsAg prevalence of 0.5-0.9% and an HCV RNA prevalence of 0.9-1.0%. The analysis was performed from a UK health service perspective, over a lifetime time horizon. Costs are reported in British pounds (GBP), and outcomes as quality adjusted life years (QALYs), with both discounted at 3.5% per year. Incremental cost-effectiveness ratios (ICER) are calculated as costs per QALY gained. A willingness-to-pay threshold of £20,000/QALY was used. The cost-effectiveness was estimated for both infections, in both ED's. RESULTS: HBV and HCV testing were highly cost-effective in both settings, with ICERs ranging from £7,177 to £12,387 per QALY gained. In probabilistic analyses, HBV testing was 89-94% likely to be cost-effective at the threshold, while HCV testing was 94-100% likely to be cost-effective, across both settings. In deterministic sensitivity analyses, testing remained cost-effective in both locations at ≥ 0.25% HBsAg prevalence, and ≥ 0.49% HCV RNA prevalence. This is much lower than the prevalence observed in the two EDs included in this study. CONCLUSIONS: HBV and HCV testing in urban EDs is highly cost-effective in the UK, and can be cost-effective at relatively low prevalence. These results should be reflected in UK and European hepatitis testing guidelines.
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OBJECTIVES: To report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy. PATIENTS AND METHODS: 102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed. RESULTS: HA insertion was completed with a 100% success rate independent of user experience, rated as 'easy' or 'very easy' in all cases. There were no postoperative complications reported. The mean (SD) recto-prostatic separation for all patients at the base, midgland and apex were 12 (±2) mm, 11 (±2) mm, and 9 (±1) mm respectively. The mean sagittal length of the implant was 43 (±5) mm. The implant was rated as symmetrical in 98% of cases. The mean rV70Gy was 1.6% (IQR 0.8-3.3%) for patients receiving 78-80Gy. The mean rV53Gy was 2.8% (IQR 1.2-4.8%) for patients receiving 60-62Gy. The median prostate size was 43.5 cc (IQR 32-57). CONCLUSION: Injection of HA was able to achieve highly symmetrical recto-prostatic separation, with new users able to produce excellent separation, particularly at the apex, achieving similar dosimetry outcomes as competent and experienced users. HA is safe, easy to use, and significantly reduced mean rV70Gy and rV53Gy compared to non-spacer patients.
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Neoplasias de la Próstata , Recto , Masculino , Humanos , Ácido Hialurónico/uso terapéutico , Próstata , Neoplasias de la Próstata/radioterapia , Marcadores FiducialesRESUMEN
Interlimb and sex-based differences in gait mechanics and neuromuscular control are common after anterior cruciate ligament reconstruction (ACLR). Following ACLR, individuals typically exhibit elevated co-contraction of knee muscles, which may accelerate knee osteoarthritis (OA) onset. While directed (medial/lateral) co-contractions influence tibiofemoral loading in healthy people, it is unknown if directed co-contractions are present early after ACLR and if they differ across limbs and sexes. The purpose of this study was to compare directed co-contraction indices (CCIs) of knee muscles in both limbs between men and women after ACLR. Forty-five participants (27 men) completed overground walking at a self-selected speed 3 months after ACLR during which quadriceps, hamstrings, and gastrocnemii muscle activities were collected bilaterally using surface electromyography. CCIs of six muscle pairs were calculated during the weight acceptance interval. The CCIs of the vastus lateralis/biceps femoris muscle pair (lateral musculature) was greater in the involved limb (vs uninvolved; p = 0.02). Compared to men, women exhibited greater CCIs in the vastus medialis/lateral gastrocnemius and vastus lateralis/lateral gastrocnemius muscle pairs (p < 0.01 and p = 0.01, respectively). Limb- and sex-based differences in knee muscle co-contractions are detectable 3 months after ACLR and may be responsible for altered gait mechanics.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Lesiones del Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Femenino , Humanos , Rodilla , Articulación de la Rodilla/fisiología , Masculino , Músculo Esquelético/fisiología , Músculo Cuádriceps/fisiologíaRESUMEN
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype-phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype-phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.
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PURPOSE: To determine the changes in physical qualities of academy rugby union players over a 10-week unsupervised off-season period. METHODS: Body mass, jump height, sprint performance, and intermittent running (30:15 IFT) of 64 academy rugby union players (age = 17.2 ± 0.4 y) were recorded before and after the off-season. RESULTS: Changes in body mass (+1.4 ± 1.3 kg), countermovement jump (-2.2 ± 1.2 cm), squat jump (-1.5 ± 1.8 cm), 10 m sprint (+0.06 ± 0.05 s), 40 m sprint (+0.13 ± 0.11 s) and 30:15 IFT (-0.8 ± 0.8 kmYh-1) were observed (P < 0.001, d = -1.77 to 0.47). Only changes in body mass were greater in forwards than backs (P = 0.036, d = 0.46). Players with higher end-of-season body mass, squat jump and 30:15 IFT had greater off-season changes (P = < 0.001 to 0.044; d = 0.63 to 0.94), whilst the pre-post difference in body mass influenced CMJ (P = 0.005, d = 0.75) and 10 m momentum change (P < 0.001, d = 1.61). CONCLUSION: Understanding the individuality of the changes in physical qualities of academy rugby union players during the off-season is important to ensure players return safely to pre-season training loads.
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Fútbol Americano , Carrera , Adolescente , Estatura , Humanos , Rugby , Estaciones del AñoRESUMEN
OBJECTIVES: To identify and map all trials in maternal health conducted in low and middle-income countries (LMIC) over the 10-year period from 2010 to 2019, to identify geographical and thematic trends, as well as comparing to global causes of maternal death and preidentified priority areas. DESIGN: Systematic scoping review. PRIMARY AND SECONDARY OUTCOME MEASURES: Extracted data included location, study characteristics and whether trials corresponded to causes of mortality and identified research priority topics. RESULTS: We searched the Cochrane Central Register of Controlled Trials database, a combined registry of trials from multiple sources. Our search identified 7269 articles, 874 of which were included for analysis. Between 2010 and 2019, maternal health trials conducted in LMICs more than doubled (50-114). Trials were conducted in 61 countries-231 trials (26.4%) were conducted in Iran. Only 225 trials (25.7%) were aligned with a cause of maternal mortality. Within these trials, pre-existing medical conditions, embolism, obstructed labour and sepsis were all under-represented when compared with number of maternal deaths globally. Large numbers of studies were conducted on priority topics such as labour and delivery, obstetric haemorrhage and antenatal care. Hypertensive disorders of pregnancy, diabetes and health systems and policy-despite being high-priority topics-had relatively few trials. CONCLUSION: Despite trials conducted in LMICs increasing from 2010 to 2019, there were significant gaps in geographical distribution, alignment with causes of maternal mortality and known research priority topics. The research gaps identified provide guidance and insight for future research conduct in low-resource settings. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/QUJP5.