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BACKGROUND: Selective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies. METHODS: We compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve. RESULTS: Compared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately. CONCLUSIONS: Multiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.
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Depresión , Comportamiento del Uso de la Herramienta , Humanos , Depresión/diagnóstico , Sensibilidad y Especificidad , Escalas de Valoración Psiquiátrica , Pruebas Diagnósticas de RutinaRESUMEN
BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease that affects children. It is crucial to detect and treat hip involvement in JIA early to prevent functional impairment and reduced quality of life. The Childhood Arthritis Radiographic Score of the Hip (CARSH) is a validated radiographic scoring system used to assess hip involvement in JIA. In this study, we aimed to determine cut-off values for CARSH scores using cluster analysis. METHODS: The study was conducted as a cross-sectional analysis and included JIA patients with hip involvement who underwent a pelvic radiograph. The same pelvic radiograph was interpreted by two experienced pediatric rheumatologists at baseline and after 3 weeks by both readers for reliability. The CARSH scores were calculated for each hip four times (twice by each reader). For the 50 hips, a total of 200 interpretations of the CARSH score were obtained. Model-based clustering was employed to identify distinct groups of CARSH score interpretations and characterize the phenotype of each cluster. RESULTS: Twenty-five children with hip involvement were included. The mean age was 13.9 ± 4.6 years. JIA subtypes were as follows: ERA in 64%, oligoarthritis in 16%, psoriatic arthritis in 12%, polyarthritis RF + in 4%, and RF - in 4% of patients. For the 200 hip interpretations, three clusters based on the level of the CARSH were identified by model-based clustering. Cluster 1 consisted of 17 CARSH score interpretations with a median score of 7 ± 3 (ranging from 1 to 15). This group primarily comprised patients with enthesitis-related arthritis (ERA) and psoriatic arthritis. Patients in cluster 1 were generally older, experienced longer diagnostic delays, and had a longer disease duration compared to the other clusters. Cluster 2 exhibited a moderate CARSH score, with an average score of 4 ± 3 (1 to 15). Patients in this group had significantly higher body weight compared to the other clusters. Cluster 3 represented the group with the least severe hip involvement, characterized by CARSH scores of 2 ± 1 (ranging from 0 to 9). This cluster had a higher proportion of male patients and higher C-reactive protein (CRP) levels than the other clusters. Regarding the individual items of the CARSH score, cluster 1 showed higher percentages of hip radiograph abnormalities such as joint space narrowing, erosions, growth abnormalities, and subchondral cysts. Cluster 2 was characterized by a high rate of acetabular sclerosis, with little to no abnormalities in other CARSH score items. Cluster 3 was the only group that exhibited hip subluxation, with minimal abnormalities in the other score items. In conclusion, this study identified three distinct groups of CARSH scores, representing varying levels of severity in hip involvement in JIA. These findings provide valuable insights for clinicians in assessing and managing JIA patients with hip involvement, enabling tailored treatment strategies based on the severity of the condition. Key Points ⢠While a Childhood Arthritis Radiographic Score of the Hip (CARSH) is a valid and reliable tool in hip-related juvenile idiopathic arthritis, its use is limited in daily practice due to the lack of available cut-off values. ⢠The cluster analysis defined three clusters based on the CARSH levels. ⢠Cluster 1 exhibited the highest score with more damage and disability. Cluster 2 involved a moderate score and more overweight patients. Cluster 3 included the least level of the score but with an active disease parameter.
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Artritis Juvenil , Artritis Psoriásica , Humanos , Niño , Masculino , Adolescente , Artritis Juvenil/diagnóstico , Calidad de Vida , Reproducibilidad de los Resultados , Estudios TransversalesRESUMEN
Introduction: Existing breakpoint guidelines are not optimal for interpreting antimicrobial resistance (AMR) data from animal studies and low-income countries, and therefore their utility for analysing such data is limited. There is a need to integrate diverse data sets, such as those from low-income populations and animals, to improve data interpretation. Gap statement: There is very limited research on the relative merits of clinical breakpoints, epidemiological cut-offs (ECOFFs) and normalized resistance interpretation (NRI) breakpoints in interpreting microbiological data, particularly in animal studies and studies from low-income countries. Aim: The aim of this study was to compare antimicrobial resistance in Escherichia coli isolates using ECOFFs, CLSI and NRI breakpoints. Methodology: A total of 59 non-repetitive poultry isolates were selected for investigation based on lactose fermentation on MacConkey agar and subsequent identification and confirmation as E. coli using chromogenic agar and uidA PCR. Kirby Bauer disc diffusion was used for susceptibility testing. For each antimicrobial agent, inhibition zone diameters were measured, and ECOFFs, CLSI and NRI bespoke breakpoints were used for resistance interpretation. Results: According to the interpretation of all breakpoints except ECOFFs, tetracycline resistance was significantly higher (TET) (67.8â-69.5â%), than those for ciprofloxacin (CIPRO) (18.6â-32.2â%), imipenem (IMI) (3.4â-35â%) and ceftazidime (CEF) (1.7â-45.8â%). Prevalence estimates of AMR using CLSI and NRI bespoke breakpoints did not differ for CEF (1.7â% CB and 1.7â% COWT), IMI (3.4â% CB and 4.0â% COWT) and TET (67.8â% CB and 69.5â% COWT). However, with ECOFFs, AMR estimates for CEF, IMI and CIP were significantly higher (45.8, 35.6 and 64.4â%, respectively; P<0.05). Across all the three breakpoints, resistance to ciprofloxacin varied significantly (32.2â% CB, 64.4â% ECOFFs and 18.6â% COWT, P<0.05). Conclusion: AMR interpretation is influenced by the breakpoint used, necessitating further standardization, especially for microbiological breakpoints, in order to harmonize outputs. The AMR ECOFF estimates in the present study were significantly higher compared to CLSI and NRI.
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Scientists are interested in determining age in subadults for several forensic purposes. High- resolution instrumental techniques are being increasingly used for age estimation, driven by the need to minimize errors; in this context, several studies have focused on the knee joint, recognized as a potential site for age examination in late adolescence. We analyzed 200 CT scans performed on Russian subjects (106 males and 94 females) between 13 and 20 years, without growth diseases, endocrine disorders, or osteodystrophy. Each subject underwent two scans, one for each leg. Two indicators were measured for each bone (femur, tibia and fibula): the entire length of the epiphyseal scar and the length of the part/s that is/are fused with metaphysis. Intra class Correlation Coefficient (ICC) was performed to evaluate the intra-operator reproducibility. The ratio between the two lengths was calculated for each bone (FemurR, TibiaR and FibulaR). The first aim was to evaluate a correlation between the ratios of the three bones and the three bones treated as a single parameter (given by the sum of the ratios) versus age. The results showed good correlations in both cases (τ a = 0.74, 0.64, 0.57 and 0.67). The second aim was to estimate the cut-offs derived from the sum of the three ratios respect to four age classes (14-15 years: cut-off ≤ 0.63, 15-16 years: cut-off ≤ 1.19, 16-17 years: cut-off ≥ 0.68 and 17-18 years: cut-off ≥ 1.49. The results from this research encourage further studies of the knee joint as an indicator of legal adult age.
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Epífisis , Articulación de la Rodilla , Masculino , Adulto , Femenino , Adolescente , Humanos , Reproducibilidad de los Resultados , Articulación de la Rodilla/diagnóstico por imagen , Epífisis/diagnóstico por imagen , Fémur , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The diagnosis of polycystic ovary syndrome (PCOS) remains challenging with international guidelines prioritising accurate cut-offs for individual diagnostic features. These diagnostic cut-offs are currently based on arbitrary percentiles, often from poorly characterised cohorts, and are dependent on variable laboratory ranges defined by assay manufacturers, limiting diagnostic accuracy. Cluster analysis is the recommended approach for defining normative cut-offs within populations for clinical syndromes. Few PCOS adult studies have applied cluster analysis, with no studies in adolescents. We aimed to define normative cut-offs for individual PCOS diagnostic features in a community-based population of adolescents using cluster analysis. DESIGN: This analysis utilised data from the Menstruation in Teenagers Study, a subgroup of the Raine Study, which is a population based prospective cohort of 244 adolescents whose mean age at PCOS assessment was 15.2 years. METHODS: K-means cluster analysis and receiver operating characteristics curves were used to define normative cut-offs for modified Ferriman-Gallwey (mFG) score, free testosterone (free T), free androgen index (FAI), and menstrual cycle length. RESULTS: Normative cut-offs for mFG, free T, FAI, and menstrual cycle lengths were 1.0, 23.4â pmol/L, 3.6, and 29 days, respectively. These corresponded to the 65th, 71st, 70th, and 59th population percentiles, respectively. CONCLUSION: In this novel study, we define the normative diagnostic criteria cut-offs in this unselected adolescent population and show that these cut-offs correspond to lower percentiles than conventional cut-offs. These findings highlight the pertinent need to re-define PCOS diagnostic cut-offs in adolescents. Validation is required in larger, multi-ethnic, and well-characterised adolescent cohorts.
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Síndrome del Ovario Poliquístico , Adulto , Femenino , Adolescente , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/epidemiología , Estudios Prospectivos , Testosterona , Análisis por ConglomeradosRESUMEN
RESEARCH QUESTION: What is the patient experience of women with high body mass index (BMI) with BMI restrictions that limit fertility care? DESIGN: Qualitative study using in-depth, semi-structured interview methodology. Interview transcripts were analysed for iterative themes in accordance with principles of grounded theory. RESULTS: Forty women with a BMI of 35 kg/m2 or higher with scheduled or completed appointment at the Reproductive Endocrinology and Infertility (REI) clinic completed an interview. Most participants experienced BMI restrictions as unjust. Many perceived that BMI restrictions on fertility care may be medically justified and were in support of weight loss discussions to improve chances of pregnancy; however, several argued that they should have autonomy to commence treatment following an individualized risk assessment. Participants offered recommendations to improve discussion of BMI restrictions and weight loss, including framing the conversation as supportive of their reproductive goals and offering proactive referral to weight loss support to prevent the perception that BMI is a categorical exclusion to future fertility care. CONCLUSIONS: Participant experiences highlight a need for enhanced strategies for communicating BMI restrictions and weight loss recommendations in ways that are perceived to be supportive of patients' fertility goals without further contributing to weight bias and stigma experienced in medical settings. Opportunities for training to mitigate experiences of weight stigma may be beneficial for clinical and non-clinical staff. Evaluation of BMI policies should be undertaken within the context of clinic policies that permit or prohibit fertility care for other high-risk groups.
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Preservación de la Fertilidad , Obesidad , Embarazo , Humanos , Femenino , Índice de Masa Corporal , Obesidad/terapia , Fertilidad , Pérdida de PesoRESUMEN
There is an urgent need for better immunoassays to measure antibody responses as part of immune-surveillance activities and to profile immunological responses to emerging SARS-CoV-2 variants. We optimised and validated an in-house conventional ELISA to identify and quantify SARS-CoV-2 spike- (S-), receptor binding domain- (RBD-), and nucleoprotein- (N-) directed IgG, IgM, and IgA binding antibodies in the Ugandan population and similar settings. Pre- and post-pandemic specimens were used to compare the utility of mean ± 2SD, mean ± 3SD, 4-fold above blanks, bootstrapping, and receiver operating characteristic (ROC) analyses in determining optimal cut-off optical densities at 450 nm (OD) for discriminating between antibody positives and negatives. "Limits of detection" (LOD) and "limits of quantitation" (LOQ) were validated alongside the assay's uniformity, accuracy, inter-assay and inter-operator precision, and parallelism. With spike-directed sensitivity and specificity of 95.33 and 94.15%, respectively, and nucleoprotein sensitivity and specificity of 82.69 and 79.71%, ROC was chosen as the best method for determining cutoffs. Accuracy measurements were within the expected CV range of 25%. Serum and plasma OD values were highly correlated (r = 0.93, p=0.0001). ROC-derived cut-offs for S-, RBD-, and N-directed IgG, IgM, and IgA were 0.432, 0.356, 0.201 (S), 0.214, 0.350, 0.303 (RBD), and 0.395, 0.229, 0.188 (N). The sensitivity and specificity of the S-IgG cut-off were equivalent to the WHO 20/B770-02 S-IgG reference standard at 100% level. Spike negative IgG, IgM, and IgA ODs corresponded to median antibody concentrations of 1.49, 3.16, and 0 BAU/mL, respectively, consistent with WHO low titre estimates. Anti-spike IgG, IgM, and IgA cut-offs were equivalent to 18.94, 20.06, and 55.08 BAU/mL. For the first time, we provide validated parameters and cut-off criteria for the in-house detection of subclinical SARS-CoV-2 infection and vaccine-elicited binding antibodies in the context of Sub-Saharan Africa and populations with comparable risk factors.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Uganda , Inmunoglobulina A , Anticuerpos Antivirales , Inmunoglobulina G , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina MRESUMEN
Background: The 2015 American Thyroid Association (ATA) Guidelines recommend the following size cut-offs based on sonographic appearances for subjecting nodules to fine-needle aspiration (FNA) biopsy: low risk: 15 mm and intermediate risk and high risk: 10 mm. Objective: We conducted a 'real-world' study evaluating the diagnostic performance of the ATA cut-offs against increased thresholds, in the interest of safely limiting FNAs. Methods: We performed a retrospective analysis of prospectively collected data on 604 nodules which were sonographically risk-stratified as per the ATA Guidelines and subsequently subjected to ultrasound-guided FNA. Nodules were cytologically stratified into 'benign' (Bethesda class 2) and 'non-benign' (Bethesda classes 3-6). We obtained the negative predictive value (NPV), accuracy, FNAs that could be spared, missed 'non-benign' cytologies and missed carcinomas on histology, according to the ATA cut-offs compared to higher cut-offs. Results: In low-risk nodules, the high performance of NPV (≈91%) is unaffected by increasing the cut-off to 25 mm, and accuracy improves by 39.4%; 46.8% of FNAs could be spared at the expense of few missed B3-B6 cytologies (7.9%) and no missed carcinomas. In intermediate-risk nodules, a 15 mm cut-off increases the NPV by 11.3% and accuracy by 40.7%. The spared FNAs approach 50%, while B3-B6 cytologies are minimal, with no missed carcinomas. In high-risk nodules, low NPV (<35%) and accuracy (<46%) were obtained regardless of cut-off. Moreover, the spared FNAs achieved at higher cut-offs involved numerous missed 'non-benign' cytologies and carcinomas. Conclusion: It would be clinically safe to increase the ATA cut-offs for FNA in low-risk nodules to 25 mm and in intermediate-risk nodules to 15 mm.
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Nowadays, slimming diet methodology works within a reduction of body mass using a decrease of dietary energy intake. However, there is no suitable method for understanding the dynamic process of body mass metabolic transformation over time. In the present paper, we have developed a biomathematic model to explain the temporal trend of body mass and its variations of people who have undergone a change in their diet using the solving equation of the model. Data relating to sex, age, body mass, and BMI were collected, and the compartmental model used to interpret the body mass trends was constructed by assuming that the mass results from the sum of the metabolic processes: catabolic, anabolic, distributive. The validation of the model was carried out by variance analysis both on the total and individual data sets. The results confirm that the trend of body mass and its variations over time depends on metabolic rates. These are specific to each individual and characterize the distribution of nutritional molecules in the various body districts and the processes catabolic, anabolic, distributive. Body mass and its variations are justified by the metabolic transformations of the nutritional quantities. This would explain why energetically equal diets can correspond to people of different body mass and that energy-different diets can correspond to people of body mass at all similar.
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Dieta , Obesidad , Índice de Masa Corporal , Ingestión de Alimentos , Ingestión de Energía , Humanos , Modelos Teóricos , Obesidad/metabolismoRESUMEN
The rising demographic of older adults worldwide has led to an increase in dementia cases. In order to ensure the proper allocation of care and resources to this clinical group, it is necessary to correctly distinguish between simulated versus bona-fide cognitive deficits typical of dementia. Performance Validity Tests (PVTs) are specifically designed to assess a lack of effort and the possible simulation of cognitive impairment. Previous research demonstrates that PVTs may be sensitive to dementia, thus inaccurately classifying real memory impairment as simulation. Here, we analyzed the sensitivity of PVTs in discriminating between dementia and simulation using receiver operating characteristic (ROC) curve analyses. Further, we examined the potential need for adjusting cut-off scores for three stand-alone (Test of Memory Malingering, Rey-15 Item Memory Test, and Coin in Hand-Extended Version) and one embedded (Reliable Digit Span) PVT for Portuguese older adults with dementia. The results showed that (1) all measures, except for the Coin in Hand- Extended version (CIH-EV), were sensitive to one or more sociodemographic and/or cognitive variables, and (2) it was necessary to adjust cut-off points for all measures. Additionally, the Rey-15 Item Memory Test did not demonstrate sufficient discriminating capacity for dementia. These results present important implications for clinical practice and the daily life of patients, as the use of incorrect cut-off points could impede patients from getting the resources they need.
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AIMS: Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF). METHODS AND RESULTS: This hypothesis was tested in a prospective diagnostic study enrolling unselected patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT-proBNP plasma concentrations were applied: first, using currently recommended cut-offs; second, using cut-offs lowered by 33% with body mass index (BMI) of 30-34.9 kg/m2 and by 50% with BMI ≥ 35 kg/m2 . Among 2038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT-proBNP as quantified by the area under the receiver-operating characteristic curve was lower in obese versus non-obese patients (0.890 vs. 0.938). For rapid AHF rule-out in obese patients, the currently recommended cut-off of 300 pg/ml achieved a sensitivity of 96.7% (95% confidence interval [CI] 93.8-98.2%), ruling out 29% of patients and missing 9 AHF patients. For rapid AHF rule-in, the age-dependent cut-off concentrations (age <50 years: 450 pg/ml; age 50-75 years: 900 pg/ml; age >75 years: 1800 pg/ml) achieved a specificity of 84.9% (95% CI 79.8-88.9%). Proportionally lowering the currently recommended cut-offs by BMI increased sensitivity to 98.2% (95% CI 95.8-99.2%), missing 5 AHF patients; reduced the proportion of AHF patients remaining in the 'gray zone' (48% vs. 26%; p = 0.002), achieving a specificity of 76.5% (95% CI 70.7-81.4%). CONCLUSIONS: Adjusting NT-proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF.
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Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Enfermedad Aguda , Anciano , Biomarcadores , Insuficiencia Cardíaca/diagnóstico , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Fragmentos de Péptidos , Estudios ProspectivosRESUMEN
The accuracy of a diagnostic test is often expressed using a pair of measures: sensitivity (proportion of test positives among all individuals with target condition) and specificity (proportion of test negatives among all individuals without target condition). If the outcome of a diagnostic test is binary, results from different studies can easily be summarized in a meta-analysis. However, if the diagnostic test is based on a discrete or continuous measure (e.g., a biomarker), several cut-offs within one study as well as among different studies are published. Instead of taking all information of the cut-offs into account in the meta-analysis, a single cut-off per study is often selected arbitrarily for the analysis, even though there are statistical methods for the incorporation of several cut-offs. For these methods, distributional assumptions have to be met and/or the models may not converge when specific data structures occur. We propose a semiparametric approach to overcome both problems. Our simulation study shows that the diagnostic accuracy is under-estimated, although this underestimation in sensitivity and specificity is relatively small. The comparative approach of Steinhauser et al. is better in terms of coverage probability, but may lead to convergence problems. In addition to the simulation results, we illustrate the application of the semiparametric approach using a published meta-analysis for a diagnostic test differentiating between bacterial and viral meningitis in children.
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Sensibilidad y Especificidad , Niño , Simulación por Computador , Humanos , ProbabilidadRESUMEN
Increasing protein demand has led to growing attention being given to the full utilization of proteins from side streams in industrial fish processing. In this study, proteins were recovered from three protein-rich side streams during Tra catfish (Pangasius hypophthalamus) processing (dark muscle; head-backbone; and abdominal cut-offs) by an optimized pH-shift process. Physicochemical characteristics of the resulting fish protein isolates (FPIs) were compared to industrial surimi from the same raw material batch. The pH had a significant influence on protein extraction, while extraction time and the ratio of the extraction solution to raw material had little effect on the protein and dry matter recoveries. Optimal protein extraction conditions were obtained at pH 12, a solvent to raw material ratio of 8, and an extraction duration of 150 min. The resulting FPI contained <10% of the fat and <15% of the ash of the raw material, while the FPI protein recovery was 83.0−88.9%, including a good amino acid profile. All FPIs had significantly higher protein content and lower lipid content than the surimi, indicating the high efficiency of using the pH-shift method to recover proteins from industrial Tra catfish side streams. The FPI made from abdominal cut-offs had high whiteness, increasing its potential for the development of a high-value product.
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We aimed to examine associations between skeletal muscle deficits and indices of poor health. Cut-points for skeletal muscle deficits were derived using data from the Geelong Osteoporosis Study and definitions from the revised European Consensus on Definition and Diagnosis and the Foundation for the National Institutes of Health. Participants (n = 665; 323 women) aged 60-96 year had handgrip strength measured by dynamometry and appendicular lean mass by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using the Timed Up and Go test. Sex-specific cut-points were equivalent to two standard deviations below the mean young reference range from the Geelong Osteoporosis Study. Indices of poor health included fractures, falls, and hospitalisations. Low trauma fractures since age 50 year (excluding skull, face, digits) were self-reported and confirmed using radiological reports. Falls (≥1 in the past 12 months) and hospitalisations (past month) were self-reported. Logistic regression models (age- and sex-adjusted) were used to examine associations. Receiver Operating Characteristic curves were applied to determine optimal cut-points for handgrip strength, Timed Up and Go, appendicular lean mass/height2, and appendicular lean mass/body mass index that discriminated poor health outcomes. There were 48 participants (6.9%) with hospitalisations, 94 (13.4%) with fractures, and 177 (25.3%) with at least one fall (≥1). For all cut-points, low handgrip strength was consistently associated with falls. There was little evidence to support an association between low appendicular lean mass, using any cut-point, and indices of poor health. Optimal cut-offs for predicting falls (≥1) were: handgrip strength 17.5 kg for women and 33.5 kg for men; Timed Up and Go 8.6 s for women and 9.9 s for men; appendicular lean mass/height2 6.2 kg/m2 for women and 7.46 kg/m2 for men; and appendicular lean mass/body mass index 0.6 m2 for women and 0.9 m2 for men. In conclusion, muscle strength and function performed better than lean mass to indicate poor health. These findings add to the growing evidence base to inform decisions regarding the selection of skeletal muscle parameters and their optimal cut-points for identifying sarcopenia.
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The effects of various purification techniques on kiwifruit enzyme characteristics (protease activity, kinetic parameters, and protein patterns) and production of wheat gluten bio-active peptides were investigated. The enzyme extract purified by ammonium sulfate precipitation method exhibited the highest protease activity (26), Km (0.04 ± 0.002 mM), Kcat /Km (40), and yield (96%). Using actinidin, the hard and soft wheat gluten subunit proteins produced antidiabetic inhibitory (α-glucosidase and α-amylase) peptides. The smallest Mw fraction of soft wheat gliadin peptide (<1 kDa) showed the highest inhibitory capacity against α-glucosidase (18.4 ± 0.7%) and α-amylase (53.3 ± 1.9%). The presence of high levels of amino acids with hydroxyl groups and proline in P3 sub-fraction had a critical role on α-glucosidase (47.2%) and α-amylase (71.2%) inhibitory activities. In conclusion, wheat gluten subunit peptides showed significant metabolic effects relevant to glucose and insulin control in vitro.
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INTRODUCTION/AIMS: Creatine kinase-MM (CK-MM) is a marker of skeletal muscle damage. Detection of elevated levels of CK-MM in newborns can enable an early suspicion of the diagnosis of Duchenne muscular dystrophy (DMD) before symptom onset. Our aim was to investigate CK-MM levels in DMD-affected and unaffected newborns using an immunoassay that measures CK-MM concentration in dried blood spots collected for routine newborn screening. METHODS: To validate the assay in our laboratory, CK-MM measurements and newborn demographic information were collected for 8584 de-identified specimens and 15 confirmed DMD patients. After analyzing validation data, CK-MM normal ranges were determined based on age of newborn at specimen collection. Subsequently, the assay was used to measure CK-MM concentration in 26 135 newborns as part of a consented pilot study to screen for DMD in New York State. Mean and median levels of CK-MM based on age of collection, in addition to the 2.5th, 50th, 97.5th, and 99.5th percentiles, were recalculated using the validation and screening data sets. RESULTS: Median CK-MM within 1 hour of birth was 109 ng/mL, rose to a high of 499 ng/mL at 25 hours of age, and then declined to 200 ng/mL at 2 days of life. The median continued to decline more slowly and then stabilized at approximately 40 ng/mL at 1 week of life. DISCUSSION: Because of the marked variability and elevated CK-MM levels observed within the first days of life, it is important to set multiple CK-MM age-related cut-offs when screening for DMD in newborns.
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Distrofia Muscular de Duchenne , Creatina Quinasa , Humanos , Recién Nacido , Distrofia Muscular de Duchenne/diagnóstico , Tamizaje Neonatal , Proyectos Piloto , Valores de ReferenciaRESUMEN
OBJECTIVES: International guidelines recommend fixed cut-off values for thyroglobulin (Tg). These cut-offs do not take potential assay differences into account. This study aimed to evaluate if different assays for Tg and Tg antibodies (TgAb) affect management guidance for differentiated thyroid cancer (DTC) patients. METHODS: In 793 samples derived from 413 patients with DTC, Tg and TgAb were simultaneously measured with two immunometric assays: Immulite 2000XPi and Kryptor compact plus. In addition, a qualitative measurement for TgAb interference (recovery test) was performed on the Kryptor compact plus platform. The extent to which different assays lead to different classifications of response to therapy was evaluated when applying the current cut-offs for Tg. RESULTS: Mean Tg concentrations were 37.4% lower with Kryptor as compared with Immulite. Applying guideline based cut-off values for Tg, 33 (4.7%) samples had a Tg-on concentration ≥1.0 µg/L with Immulite and <1.0 µg/L with Kryptor. Of the samples tested as TgAb+ with at least one assay (n=125), 68 (54.4%) samples showed discrepancy in TgAb status. Differences between Immulite and Kryptor measurements resulted in a change in the response to therapy classification in 94 (12.0%) measurements derived from 67 (16.2%) individual patients. CONCLUSIONS: A substantial portion of DTC patients were classified differently dependent on which Tg and TgAb assays are used, when applying the cut-off values as defined in clinical guidelines. Such differences can significantly affect clinical management. In the context of large between-method variation, the recommended Tg cut-offs in guidelines should be used with wisdom rather than as fixed cut-offs.
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Adenocarcinoma , Neoplasias de la Tiroides , Autoanticuerpos , Bioensayo , Humanos , TiroglobulinaRESUMEN
Lean body mass (LBM) comprises organs and muscle, which are the primary determinants of energy expenditure and regulation of glucose and lipid metabolism. Excessive abdominal fat is associated with metabolic abnormality. Little is known about the relationship between metabolic abnormality and LBM and waist circumference (WC), especially in the Asian general population. The aim of this study was to clarify this relationship. We performed a cross-sectional study with 499,648 subjects who received health check-ups at 16 health promotion centers in 13 Korean cities between January 2018 and October 2019. The subjects were categorized into four groups: (a) High (H)-RLBM (relative lean body mass)/Normal (N)-WC, (b) High-RLBM/Abnormal (A)-WC, (c) Low (L)-RLBM/Normal-WC, and (d) Low-RLBM/Abnormal-WC. RLBM was calculated using fat mass data that were estimated via bioelectrical impedance analysis. L-RLBM/A-WC was significantly associated with metabolically unhealthy status (OR: 4.40, 95% CI: 4.326-4.475) compared to H-RLBM/N-WC. L-RLBM/N-WC (OR: 2.170, 95% CI: 2.122-2.218) and H-RLBM/A-WC (OR: 2.713, 95% CI: 2.659-2.769) were also significantly related to metabolic unhealthy status. The cut-offs of RLBM for predicting metabolic syndrome (MetS) were 74.9 in males and 66.4 in females (p < 0.001). L-RLBM and A-WC are associated with metabolic abnormality in the Korean general population. RLBM is an anthropometric index that can be used to predict MetS in primary health care.