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1.
Health Aff (Millwood) ; 43(7): 950-958, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38950303

RESUMEN

Value-based payment has been promoted for increasing quality, controlling spending, and improving patient and practitioner experience. Meanwhile, needed reforms to fee-for-service payment (the Medicare Physician Fee Schedule) have been ignored as policy makers seek to move payment toward alternatives, even though the fee schedule is an intrinsic part of Alternative Payment Models. In this article, we show how value-based payment and the fee schedule should be viewed as complementary, rather than as separate silos. We trace the origins of embedded flaws in the fee schedule that must be fixed if value-based payment is to succeed. These include payment distortions that directly compromise value by overpaying for certain procedures and imaging services while underpaying for services that add value for beneficiaries. We also show how the fee schedule can accommodate bundled payments and population-based payments that are central to Alternative Payment Models. We draw two conclusions. First, the Centers for Medicare and Medicaid Services should correct misvalued services and establish a hybrid payment for primary care that blends fee-for-service and population-based payment. Second, Congress should alter the thirty-five-year-old statutory basis for setting Medicare fees to allow CMS to explicitly consider policy priorities such as workforce shortages in refining fee levels.


Asunto(s)
Tabla de Aranceles , Planes de Aranceles por Servicios , Medicare , Estados Unidos , Medicare/economía , Humanos , Planes de Aranceles por Servicios/economía , Médicos/economía , Mecanismo de Reembolso
2.
Pediatr Res ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834782

RESUMEN

BACKGROUND: Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. METHODS: Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. RESULTS: The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. CONCLUSION: EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. IMPACT: Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.

3.
PLOS Glob Public Health ; 4(5): e0003186, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781145

RESUMEN

Low vaginal self-sampling has been pioneered as an important development to improve uptake of cervical screening globally. Limited research is available in specific patient groups in the UK exploring views around self-sampling to detect high-risk human papillomavirus (hrHPV) DNA. Therefore, we explored patient views to support development of a novel point-of-care self-sampling cervical cancer screening device, by undertaking a cross-sectional semi-structured questionnaire survey to explore preferences, acceptability, barriers and facilitators around self-sampling. Patients attending a colposcopy clinic, 25-64 years old, were invited to participate after having carried out a low vaginal self-sample using a regular flocked swab. Participants self-completed an anonymous 12-point questionnaire. Quantitative data were analysed in MS Excel and Graphpad Prism, and qualitative data with Nvivo. We recruited 274 patients with a questionnaire response rate of 76%. Acceptability of self-sampling was high (95%, n = 187/197; Cronbachs-α = 0.778). Participants were asked their choice of future screening method: a) low vaginal self-sampling, b) healthcare professional collected vaginal swab, c) cervical brush sample with healthcare professional speculum examination, or d) no preference. Preferences were: a) 37% (n = 74/198), b) 19% (n = 37/198); c) 9% (n = 17/198), and d) 35% (n = 70/198), showing no single option as a strong preference. Key motivators were: Test simplicity (90%, n = 170/190), speed (81%, n = 153/190) and less pain (65%, n = 123/190). Barriers included lack of confidence taking the sample (53%, n = 10/19), resulting in preference for a healthcare professional sample (47%, n = 9/19). Whilst self-sampling showed high acceptability, lack of strong preference for screening method may reflect that respondents attending colposcopy are already engaged with screening and have differing perception of cervical cancer risk. This group appear less likely to 'switch' to self-sampling, and it may be better targeted within primary and community care, focusing on under-screened populations. Any shift in this paradigm in the UK requires comprehensive education and support for patients and providers.

4.
J Med Genet ; 60(5): 440-449, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36319079

RESUMEN

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.


Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Neoplasias Ováricas , Femenino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Diagnóstico Tardío , Predisposición Genética a la Enfermedad/epidemiología , Células Germinativas/patología , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/economía , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Ovariectomía , Medicina Estatal/economía , Salpingectomía , Reino Unido/epidemiología , Vigilancia de la Población , Análisis de Costo-Efectividad
5.
EBioMedicine ; 81: 104106, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35779494

RESUMEN

BACKGROUND: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH. METHODS: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity. Next, an efficacy study was performed assessing the effects of treprostinil administration at 900 and 1500ng/kg/min from gestational day (GD) 16 until term (GD 21) in CDH and control pups. Pulmonary vascular and airway morphometry, lung mechanics, and expression patterns of genes implicated in the prostaglandin vasoactive pathway were studied. FINDINGS: In rats maternal administration of 1500ng/kg/min treprostinil reached target foetal concentrations, with no detrimental maternal or foetal side-effects. Prenatal exposure to 900 and 1500 ng/kg/min treprostinil reduced the medial wall thickness (%MWT) (CDH·900, 38.5± 8·4%; CDH.1500, 40·2±9·7%; CDH, 46·6±8·2%; both p < 0·0001) in rat pups with CDH, however increased the %MWT in normal foetuses (C.T.900, 36·6±11·1%; C.T.1500, 36·9±9·3%; C.P., 26·9±6·2%; both p < 0·001). Pulmonary airway development, lung hypoplasia and pulmonary function were unaffected by drug exposure. INTERPRETATION: In pregnant rats maternally administered treprostinil crosses the placenta, attains foetal target concentrations, and is well tolerated by both mother and foetuses. This report shows a significant reduction of pulmonary arteriole muscularization with prenatal treprostinil in a nitrofen rat model, supporting the promise of this treatment approach for PH of CDH. FUNDING: United Therapeutics Corporation provided treprostinil and financial support (ISS-2020-10879).


Asunto(s)
Hernias Diafragmáticas Congénitas , Hipertensión Pulmonar , Enfermedades Pulmonares , Animales , Modelos Animales de Enfermedad , Epoprostenol/análogos & derivados , Femenino , Hernias Diafragmáticas Congénitas/etiología , Hernias Diafragmáticas Congénitas/genética , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Pulmón/metabolismo , Enfermedades Pulmonares/metabolismo , Fenotipo , Embarazo , Ratas
7.
Sports Biomech ; 21(5): 604-621, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-31573420

RESUMEN

In the sprint start, a defined sequence of distinct response delays occurs before the athlete produces a movement response. Excitation of lower limb muscles occurs prior to force production against the blocks, culminating in a movement response. The time delay between muscle excitation and movement, electromechanical delay (EMD), is considered to influence sprint start response time (SSRT). This study examined the delay in sprint start performance from EMD of the triceps surae muscle and examined whether certain sprinters gain an advantage in SSRT. Nineteen experienced sprinters performed sprint starts from blocks, with SSRT measured by an International Association of Athletics Federations (IAAF)-approved starting block system. EMD times were detected during a heel-lift experiment. Using revised SSRT limits, based on concerns over the validity of the IAAF 100 ms false start limit, EMD produced a significant moderate correlation with SSRT (r = 0.572, p = 0.011). Regression analysis determined that together, EMD and signal processing time (the delay between the auditory signal and muscle excitation) accounted for 37% of the variance in SSRT. Initial results suggest EMD is part of the response time process and that certain athletes may gain a performance advantage due to reduced EMD.


Asunto(s)
Pierna , Músculo Esquelético , Fenómenos Biomecánicos , Humanos , Movimiento , Músculo Esquelético/fisiología , Tiempo de Reacción/fisiología
8.
Clin Nutr ESPEN ; 45: 312-321, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34620334

RESUMEN

BACKGROUND: Accurate early risk-prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated maternal risk-factors and parameters of body-composition to develop a prediction model for GDM in early gestation. METHODS: A prospective observational study was undertaken. Pregnant women aged between 18 and 50 y of age with gestational age between 10 and 16 weeks were included in the study. Women aged ≤18 y, twin-pregnancies, known foetal anomaly or pre-existing condition affecting oedema status were excluded. 8-point-skinfold thickness (SFT), mid-upper-arm-circumference (MUAC), waist, hip, weight and ultrasound measurements of subcutaneous (SAT) and visceral abdominal-adipose (VAT) were measured. Oral-glucose-tolerance-test (OGTT) for GDM diagnosis was undertaken at 28 weeks gestation. Binomial logistic-regression models were used to predict GDM. ROC-analysis determined discrimination and concordance of model and individual variables. RESULTS: 188 women underwent OGTT at ~28 weeks gestation. 20 women developed GDM. BMI (24.7 kg m-2 (±6.1), 29.9 kg m-2 (±7.8), p = 0.022), abdominal SAT(1.32 cm (CI 1.31, 1.53), 1.99 cm (CI 1.64, 2.31), p = 0.027), abdominal VAT(0.78 cm (CI 0.8, 0.96), 1.41 cm (CI 1.11, 1.65), p = 0.002), truncal SFT (84.8 mm (CI 88.2, 101.6), 130.4 mm (CI 105.1, 140.1), p = 0.010), waist (79.8 cm (CI 80.3, 84.1), 90.3 cm (CI 85.9, 96.2), p = 0.006) and gluteal hip (94.3 cm (CI 93.9, 98.0), 108.6 cm (CI 99.9, 111.6), p = 0.023) were higher in GDM vs. non-GDM. After screening variables for inclusion into the multivariate model, family history of diabetes, previous perinatal death, overall insulin resistant condition, abdominal SAT and VAT, 8-point SFT, MUAC and weight were included. The combined multivariate prediction model achieved an excellent level of discrimination, with an AUC of 0.860 (CI 0.774, 0.945) for GDM. CONCLUSIONS: An early gestation risk prediction model, incorporating known risk-factors, and parameters of body-composition, accurately identify pregnant women in their first-trimester who developed GDM later on in gestation. This methodology could be used clinically to identify at-risk pregnancies, and target specific treatment through referred services to those mothers who would most benefit.


Asunto(s)
Diabetes Gestacional , Composición Corporal , Preescolar , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Lactante , Embarazo , Primer Trimestre del Embarazo , Grosor de los Pliegues Cutáneos
10.
J Chromatogr A ; 1656: 462495, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34537663

RESUMEN

The abundance and composition of matrix compounds in fire debris samples undergoing ignitable liquid residue analysis frequently leads to inconclusive results, which can be diminished by applying comprehensive two-dimensional gas chromatography (GC × GC). Method development must be undertaken to fully utilize the potential of GC × GC by maximizing separation space and resolution.. The three main areas to consider for method development are column selection, modulator settings and parameter optimization. Seven column combinations with different stationary phase chemistry, column dimensions and orthogonality were assessed for suitability based on target compound selectivity, retention, resolution, and peak shapes, as well as overall peak capacity and area use. Using Box-Behnken design of experimentation (DoE), the effect of modulator settings such as flow ratio and loop fill capacity were evaluated using carbon loading potential, dilution effect, as well as target peak amplitude and skewing effect. The run parameters explored for parameter optimization were oven programming, inlet pressure (column flow rate), and modulation period. Comparing DoE approaches, Box-Behnken and Doehlert designs assessed sensitivity, selectivity, peak capacity, and wraparound; alongside target peak retention, resolution, and shape evaluation. Certified reference standards and simulated wildfire debris were used for method development and verification, and wildfire debris case samples scrutinized for method validation. The final method employed a low polarity column (5% diphenyl) coupled to a semi-polar column (50% diphenyl) and resulted in an average Separation Number (SN) exceeding 1 in both dimensions after optimization. Separation Numbers of 18.16 for first and 1.46 for second dimension without wraparound for compounds with at least four aromatic rings signified successful separation of all target compounds from varied matrix compositions and allowed for easy visual comparison of extracted ion profiles. Mass spectrometry (MS) was required during validation to differentiate ions where no baseline separation between target compounds and extraneous matrix compounds was possible. The resulting method was evaluated against ASTM E1618 and found to be an ideal routine analysis method providing great resolution of target compounds from interferences and excellent potential for ILR classification within a complex sample matrix.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Técnicas de Dilución del Indicador , Espectrometría de Masas
11.
Sci Total Environ ; 796: 148742, 2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34375198

RESUMEN

Occupational exposure to oil fumes, organophosphates, halogenated flame retardants, and other volatile and semi-volatile contaminants is a concern within the aviation industry. There is no current consensus on the risk attributed to exposure to these chemical classes within the aircraft cabin. Contaminant concentrations rarely exceed conventional air quality guidelines, but concerns have been raised about these guidelines' applicability within the aircraft environment. This systematic review, the largest and most comprehensive completed to date on the subject matter, aims to synthesize the existing research related to chemical and other exposures inside the aircraft cabin to determine the occupational risk that may be attributed said exposure, as well as, determine knowledge gaps in source, pathway, and receptor that may exist. The Science Direct, Scopus, and Web of Science databases were queried with five search terms generating 138 manuscripts that met acceptance criteria and screening. Several potential areas requiring future examination were identified: Potable water on aircraft should be examined as a potential source of pollutant exposure, as should air conditioning expansion turbines. Historical exposure should also be more fully explored, and non-targeted analysis could provide valuable information to comprehend the aircraft cabin exposome. Occupational risk under typical flight scenarios appears to be limited for most healthy individuals. Contaminants of concern were demonstrated to be extant within the cabin, however the concentrations under normal circumstances do not appear to be individually responsible for the symptomologies that are present in impacted individuals. Questions remain regarding those that are more vulnerable or susceptible to exposure. Additionally, establishing the effects of chronic low dose exposure and exposure to contaminant mixtures has not been satisfied. The risk of acute exposure in mitigable fume events is substantial, and technological solutions or the replacement of compounds of concern for safer alternatives should be a priority.


Asunto(s)
Contaminación del Aire Interior , Retardadores de Llama , Exposición Profesional , Contaminación del Aire Interior/análisis , Aeronaves , Retardadores de Llama/análisis , Humanos , Exposición Profesional/análisis , Organofosfatos
12.
Stem Cells ; 39(9): 1137-1144, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33932319

RESUMEN

Nodal is a transforming growth factor-ß (TGF-ß) superfamily member that plays a number of critical roles in mammalian embryonic development. Nodal is essential for the support of the peri-implantation epiblast in the mouse embryo and subsequently acts to specify mesendodermal fate at the time of gastrulation and, later, left-right asymmetry. Maintenance of human pluripotent stem cells (hPSCs) in vitro is dependent on Nodal signaling. Because it has proven difficult to prepare a biologically active form of recombinant Nodal protein, Activin or TGFB1 are widely used as surrogates for NODAL in hPSC culture. Nonetheless, the expression of the components of an endogenous Nodal signaling pathway in hPSC provides a potential autocrine pathway for the regulation of self-renewal in this system. Here we review recent studies that have clarified the role of Nodal signaling in pluripotent stem cell populations, highlighted spatial restrictions on Nodal signaling, and shown that Nodal functions in vivo as a heterodimer with GDF3, another TGF-ß superfamily member expressed by hPSC. We discuss the role of this pathway in the maintenance of the epiblast and hPSC in light of these new advances.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Células Madre Pluripotentes , Animales , Diferenciación Celular/fisiología , Humanos , Proteína Nodal/genética , Proteína Nodal/metabolismo , Células Madre Pluripotentes/metabolismo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo
13.
Physiol Meas ; 42(3)2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725688

RESUMEN

Objective. Accurate identification of surface electromyography (EMG) muscle onset is vital when examining short temporal parameters such as electromechanical delay. The visual method is considered the 'gold standard' in onset detection. Automatic detection methods are commonly employed to increase objectivity and reduce analysis time, but it is unclear if they are sensitive enough to accurately detect EMG onset when relating them to short-duration motor events.Approach. This study aimed to determine: (1) if automatic detection methods could be used interchangeably with visual methods in detecting EMG onsets (2) if the Teager-Kaiser energy operator (TKEO) as a conditioning step would improve the accuracy of popular EMG onset detection methods. The accuracy of three automatic onset detection methods: approximated generalized likelihood ratio (AGLR), TKEO, and threshold-based method were examined against the visual method. EMG signals from fast, explosive, and slow, ramped isometric plantarflexor contractions were evaluated using each technique.Main results. For fast, explosive contractions, the TKEO was the best-performing automatic detection method, with a low bias level (4.7 ± 5.6 ms) and excellent intraclass correlation coefficient (ICC) of 0.993, however with wide limits of agreement (LoA) (-6.2 to +15.7 ms). For slow, ramped contractions, the AGLR with TKEO conditioning was the best-performing automatic detection method with the smallest bias (11.3 ± 32.9 ms) and excellent ICC (0.983) but produced wide LoA (-53.2 to +75.8 ms). For visual detection, the inclusion of TKEO conditioning improved inter-rater and intra-rater reliability across contraction types compared with visual detection without TKEO conditioning.Significance. In conclusion, the examined automatic detection methods are not sensitive enough to be applied when relating EMG onset to a motor event of short duration. To attain the accuracy needed, visual detection is recommended. The inclusion of TKEO as a conditioning step before visual detection of EMG onsets is recommended to improve visual detection reliability.


Asunto(s)
Sustancias Explosivas , Músculo Esquelético , Computadores , Electromiografía , Contracción Isométrica , Contracción Muscular , Reproducibilidad de los Resultados
14.
Sports Med ; 51(1): 21-31, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33125639

RESUMEN

The sprint start in athletics is strictly controlled to ensure the fairness of competition. World athletics (WA)-certified start information systems (SIS) record athletes' response times in competition to ensure that no athletes gain an unfair advantage by responding in < 100 ms after the start signal. This critical review examines the legitimacy of the 100 ms rule, the factors that affect response times and the technologies and rules that support the regulation of the start in competition. The review shows that several SIS use different technologies to deliver the start signal and record response time (RT). The lack of scientific evidence about the definition of the 100 ms false start threshold by the WA is criticized in the literature and the 100 ms rule is challenged. SIS technologies, expertise and sex appear to affect the RT detected in competition. A lack of standardization in event detection has led to validity and reliability problems in RT determination. The onset of the foot response on the blocks is currently used to assess RT in athletics via block-mounted sensors; however, research shows that the onset of arm force reaction is the first detectable biomechanical event in the start. Further research and development should consider whether the onset of arm force can be used to improve the false start detection in competition. Further research is also needed to develop a precise understanding of the event sequence and motor control of the start to improve the SIS technology and rigorously determine the minimum limit of RT in the sprint start.


Asunto(s)
Rendimiento Atlético , Carrera , Atletas , Humanos , Tiempo de Reacción , Reproducibilidad de los Resultados
15.
Front Immunol ; 11: 622114, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33613556

RESUMEN

Common variable immunodeficiency (CVID) is the most frequently diagnosed primary antibody deficiency. About half of CVID patients develop chronic non-infectious complications thought to be due to intrinsic immune dysregulation, including autoimmunity, gastrointestinal disease, and interstitial lung disease (ILD). Multiple studies have found ILD to be a significant cause of morbidity and mortality in CVID. Yet, the precise mechanisms underlying this complication in CVID are poorly understood. CVID ILD is marked by profound pulmonary infiltration of both T and B cells as well as granulomatous inflammation in many cases. B cell depletive therapy, whether done as a monotherapy or in combination with another immunosuppressive agent, has become a standard of therapy for CVID ILD. However, CVID is a heterogeneous disorder, as is its lung pathology, and the precise patients that would benefit from B cell depletive therapy, when it should administered, and how long it should be repeated all remain gaps in our knowledge. Moreover, some have ILD recurrence after B cell depletive therapy and the relative importance of B cell biology remains incompletely defined. Developmental and functional abnormalities of B cell compartments observed in CVID ILD and related conditions suggest that imbalance of B cell signaling networks may promote lung disease. Included within these potential mechanisms of disease is B cell activating factor (BAFF), a cytokine that is upregulated by the interferon gamma (IFN-γ):STAT1 signaling axis to potently influence B cell activation and survival. B cell responses to BAFF are shaped by the divergent effects and expression patterns of its three receptors: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). Moreover, soluble forms of BAFF-R, TACI, and BCMA exist and may further influence the pathogenesis of ILD. Continued efforts to understand how dysregulated B cell biology promotes ILD development and progression will help close the gap in our understanding of how to best diagnose, define, and manage ILD in CVID.


Asunto(s)
Linfocitos B/inmunología , Inmunodeficiencia Variable Común/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Pulmón/inmunología , Linfocitos B/patología , Inmunodeficiencia Variable Común/patología , Humanos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/patología
17.
BMC Med Imaging ; 19(1): 95, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31847832

RESUMEN

BACKGROUND: Excess abdominal adiposity cause metabolic disturbances, particularly in pregnancy. Methods of accurate measurement are limited in pregnancy due to risks associated with these procedures. This study outlines a non-invasive methodology for the measurement of adipose tissue in pregnancy and determines the intra- and inter-observer reliability of ultrasound (US) measurements of the two components of adipose tissue (subcutaneous (SAT) and visceral adipose tissue (VAT)) within a pregnant population. METHODS: Thirty pregnant women were recruited at the end of their first trimester, from routine antenatal clinic at the University Maternity Hospital Limerick, Ireland. Measurements of adipose tissue thickness were obtained using a GE Voluson E8 employing a 1-5 MHz curvilinear array transducer. Two observers, employing methodological rigour in US technique, measured thickness of adipose tissue three times, and segmented the US image systematically in order to define measurements of SAT and VAT using specifically pre-defined anatomical landmarks. RESULTS: Intra-observer and inter-observer precision was assessed using Coefficient of Variation (CV). Measurements of SAT and total adipose for both observers were < 5% CV and < 10% CV for VAT in measures by both observers. Inter-observer reliability was assessed by Limits of Agreement (LoA). LoA were determined to be - 0.45 to 0.46 cm for SAT and - 0.34 to 0.53 cm for VAT values. Systematic bias of SAT measurement was 0.01 cm and 0.10 cm for VAT. Inter-observer precision was also assessed by coefficient of variation (CV: SAT, 3.1%; VAT, 7.2%; Total adipose, 3.0%). CONCLUSION: Intra-observer precision was found to be acceptable for measures of SAT, VAT and total adipose according to anthropometric criterion, with higher precision reported in SAT values than in VAT. Inter-observer reliability assessed by Limits-Of-Agreement (LoA) confirm anthropometrically reliable to 0.5 cm. Systematic bias was minimal for both measures, falling within 95% confidence intervals. These results suggest that US can produce reliable, repeatable and accurate measures of SAT and VAT during pregnancy.


Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Grasa Intraabdominal/diagnóstico por imagen , Grasa Subcutánea/diagnóstico por imagen , Femenino , Edad Gestacional , Humanos , Variaciones Dependientes del Observador , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Interpretación de Imagen Radiográfica Asistida por Computador , Reproducibilidad de los Resultados , Ultrasonografía
18.
Phys Ther Sport ; 40: 59-65, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31479981

RESUMEN

OBJECTIVES: To investigate factors associated with injury in amateur male and female rugby union players. DESIGN: A prospective cohort study. SETTING: Amateur rugby clubs in Ireland. PARTICIPANTS: Male (n = 113) and female (n = 24) amateur rugby union players from 5 of the top 58 amateur clubs in Ireland. MAIN OUTCOME MEASURES: Pre-season testing included physical tests assessing hamstring flexibility, dorsiflexion range of movement, adductor muscle strength and foot position. Wellness questionnaires assessed sleep quality (PSQI), coping skills (ACSI-28) and support levels (PASS-Q). Players were monitored throughout the season for injury. RESULTS: The time-loss match injury incidence rate was 48.2/1000 player hours for males and 45.2/1000 player hours for females. Two risk profiles emerged involving; 'age + navicular drop + training pitch surface' (53%) and 'age + navicular drop + groin strength' (16%). An inverse relationship between groin strength and groin injury was found for the 'backs' players (-0.307, p < 0.05). Using the PSQI, 61% of players had poor sleep quality, however no relationship between the wellness questionnaires and injury was found. CONCLUSION: Two injury risk profiles emerged, associated with subsequent injury occurrence. Using these risk profiles, individualized prevention strategies may be designed regarding deficits in groin muscle strength and identifying foot alignment.


Asunto(s)
Traumatismos en Atletas/epidemiología , Fútbol Americano/lesiones , Estado de Salud , Fuerza Muscular , Músculo Esquelético/fisiopatología , Adulto , Atletas , Femenino , Ingle/lesiones , Humanos , Incidencia , Irlanda , Traumatismos de la Pierna/epidemiología , Masculino , Músculo Esquelético/lesiones , Estudios Prospectivos , Adulto Joven
19.
Phys Ther Sport ; 35: 79-88, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30472491

RESUMEN

OBJECTIVES: To describe the development, implementation and evaluation of a comprehensive injury surveillance system. DESIGN: The four phases; i) A survey of 58 medical professionals working in amateur rugby. ii) The design of a web-based injury surveillance system (IRISweb). iii) Recruitment of 21 of the top 58 amateur clubs to use IRISweb. iv) An evaluation survey of the 21 participating clubs. SETTING: Irish amateur rugby clubs. PARTICIPANTS: Medical professionals working in amateur rugby. MAIN OUTCOME MEASURES: Phase one investigated the injury monitoring practices in operation prior to the IRIS project. Phase four investigated the effectiveness and usefulness of IRISweb. RESULTS: Twenty-one clubs were recruited, however 2 clubs failed to provide a full season of data (10% dropout rate). Eighty-two percent of the remaining 19 clubs rated IRISweb as 'good' or 'very good'. Facilitators of injury surveillance were; increased player adherence (65%) and notifications to update the system (59%), however, poor player adherence (71%) and medical staff availability (24%) were the main barriers. CONCLUSIONS: The IRIS project is the first prospective long-term injury surveillance system in Irish amateur rugby, effectively tracking injuries to guide future evidence-based injury prevention strategies. This study highlights facilitators and barriers to injury surveillance within amateur sport.


Asunto(s)
Traumatismos en Atletas/epidemiología , Monitoreo Epidemiológico , Fútbol Americano/lesiones , Internet , Atletas , Femenino , Humanos , Irlanda , Masculino , Encuestas y Cuestionarios
20.
Sci Rep ; 8(1): 13327, 2018 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-30190503

RESUMEN

Aldehyde dehydrogenases (ALDH) form a superfamily of dimeric or tetrameric enzymes that catalyze the oxidation of a broad range of aldehydes into their corresponding carboxylic acids with the concomitant reduction of the cofactor NAD(P) into NAD(P)H. Despite their varied polypeptide chain length and oligomerisation states, ALDHs possess a conserved architecture of three domains: the catalytic domain, NAD(P)+ binding domain, and the oligomerization domain. Here, we describe the structure and function of the ALDH from Thermus thermophilus (ALDHTt) which exhibits non-canonical features of both dimeric and tetrameric ALDH and a previously uncharacterized C-terminal arm extension forming novel interactions with the N-terminus in the quaternary structure. This unusual tail also interacts closely with the substrate entry tunnel in each monomer providing further mechanistic detail for the recent discovery of tail-mediated activity regulation in ALDH. However, due to the novel distal extension of the tail of ALDHTt and stabilizing termini-interactions, the current model of tail-mediated substrate access is not apparent in ALDHTt. The discovery of such a long tail in a deeply and early branching phylum such as Deinococcus-Thermus indicates that ALDHTt may be an ancestral or primordial metabolic model of study. This structure provides invaluable evidence of how metabolic regulation has evolved and provides a link to early enzyme regulatory adaptations.


Asunto(s)
Aldehído Deshidrogenasa/química , Proteínas Bacterianas/química , Evolución Molecular , Thermus thermophilus/enzimología , Aldehído Deshidrogenasa/genética , Proteínas Bacterianas/genética , Dominios Proteicos , Estructura Cuaternaria de Proteína , Thermus thermophilus/genética
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