Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development.

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Lever sign test shows high diagnostic accuracy for anterior cruciate ligament injuries: A systematic review and meta-analysis of 3299 observations.

PURPOSE: Injuries of the anterior cruciate ligament (ACL) are common knee injuries among active and younger patients. The Lever Sign Test (LST) is a relatively newer test, of which the accuracy is disputed in the existing literature. The aim of this study was to assess the accuracy with and without anesthesia of the Lever Sign test in the literature. METHODS: PRISMA guidelines were followed, studies were identified using PubMed, EMBASE and Google Scholar. All studies that reported accuracy of LST performed by a clinical professional were included. Integrity of ACL was confirmed using magnetic resonance imaging or arthroscopy. Sensitivity and specificity were calculated using uni- and bivariate methods. RESULTS: After inclusion, 3299 observations in 2516 patients were included from 23 studies. Mean age was 31.8 years and 64.2% were male. Without anesthesia, sensitivity was 79.2% (95% CI 68.7-86.9) and specificity was 92.0% (95% CI 82.2-96.6). An area under the curve (AUC) of 86.1% was found. With anesthesia, sensitivity was 86.6% (95% CI 68.0-95.2), specificity was 93.4% (95% CI 84.5-97.3) and the AUC was 91.6%. CONCLUSION: The Lever Sign test shows very good to excellent accuracy for ACL injury, and is a useful tool for clinical practice.

A spectro-temporal modulation test for predicting speech reception in hearing-impaired listeners with hearing aids.

Spectro-temporal modulation (STM) detection sensitivity has been shown to be associated with speech-in-noise reception in hearing-impaired (HI) individuals. Based on previous research, a recent study [Zaar, Simonsen, Dau, and Laugesen (2023). Hear Res 427:108650] introduced an STM test paradigm with audibility compensation, employing STM stimulus variants using noise and complex tones as carrier signals. The study demonstrated that the test was suitable for the target population of elderly individuals with moderate-to-severe hearing loss and showed promising predictions of speech-reception thresholds (SRTs) measured in a realistic set up with spatially distributed speech and noise maskers and linear audibility compensation. The present study further investigated the suggested STM test with respect to (i) test-retest variability for the most promising STM stimulus variants, (ii) its predictive power with respect to realistic speech-in-noise reception with non-linear hearing-aid amplification, (iii) its connection to effects of directionality and noise reduction (DIR+NR) hearing-aid processing, and (iv) its relation to DIR+NR preference. Thirty elderly HI participants were tested in a combined laboratory and field study, collecting STM thresholds with a complex-tone based and a noise-based STM stimulus design, SRTs with spatially distributed speech and noise maskers using hearing aids with non-linear amplification and two different levels of DIR+NR, as well as subjective reports and preference ratings obtained in two field periods with the two DIR+NR hearing-aid settings. The results indicate that the noise-carrier based STM test variant (i) showed optimal test-retest properties, (ii) yielded a highly significant correlation with SRTs (R2=0.61) exceeding and complementing the predictive power of the audiogram, (iii) yielded significant correlation (R2=0.51) with the DIR+NR-induced SRT benefit, and (iv) did not provide significant correlation with subjective preference for DIR+NR settings in the field. Overall, the suggested STM test represents a valuable tool for diagnosing speech-reception problems that remain when hearing-aid amplification has been provided and the resulting need for and benefit from DIR+NR hearing-aid processing.

Association between three-dimensional motion analysis of the thumb and clinical parameters in patients with carpal tunnel syndrome.

We analysed the relationship between motor dysfunction of the thumb and the clinical parameters of carpal tunnel syndrome using three-dimensional motion analysis. This single-centred, prospective study included 65 hands in 51 patients with idiopathic carpal tunnel syndrome and 30 healthy hands. Three-dimensional thumb kinematics were acquired using a motion capture system with a retroreflective surface-based marker method. The trajectory area of thumb tip, adduction and abduction of the trapeziometacarpal joints and metacarpophalangeal joints were correlated with the clinical parameters. There was no significant correlation between the results of motion analysis values and patient-reported outcomes measures. Thumb movement disorder associated with carpal tunnel syndrome affected specific activities of daily living based on the pinching movements, such as 'writing' and 'buttoning clothes' among the patient-reported outcome measure items.Level of evidence: III.

Longitudinal Analysis of the ASES and Constant-Murley Scores, and the Internal Rotation/Shift and Jobe Tests Following Arthroscopic Repair of Supraspinatus Lesions.

It is essential to investigate patients post-surgery using functional surveys like the American Shoulder and Elbow Surgeons Shoulder (ASES) and the Constant-Murley shoulder (CMS) scores, as well as clinical tests, such as the Internal Rotation and Shift (IRO/Shift) and Jobe tests. In this study, 51 out of an initial 87 patients underwent an arthroscopic supraspinatus repair (22 single-row, 16 double-row, 13 debridement). Testing occurred pre-surgery, and 3 and 6 months post-surgery. Both surveys showed significant improvements over time among all 87 patients, but there were no differences between groups (lesion/no lesion) (p > 0.815) or time × group (p > 0.895). The IRO/Shift test showed a stronger ability to distinguish between both groups (positive vs. negative) with respect to the ASES and CMS scores over time, but the Jobe test did not (p > 0.100). Improvements in the CMS scores and the Jobe test were lower following repair compared to the ASES and IRO/Shift test. Most patients returned to adequate levels of functional abilities at 6 months post-surgery. The time required to return to activities of daily living and negative clinical tests was longer for the double-row repair patients compared to the single-row and debridement groups. In conclusion, both the functional surveys and the clinical tests demonstrated improvements following surgery.

A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation.

The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children's Auditory Processing Performance Scale, the Fisher's Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires.

[Management Practice of Outsourcing Hospital Tests to Independent Clinical Laboratories].

With the development of medical technology and the deepening of medical reform, hospital laboratory test continues to expand. Affected by factors such as technology and cost, the business of outsourcing laboratory test to independent clinical laboratories develops rapidly. However, this cooperation mode has not been carried out for a long time and lacks systematic management experience. Through the analysis of the motivation of hospital delivery, this study expounds the classification, judgment basis and requirements for suppliers of third-party clinical laboratory delivery, as well as the operation practice of laboratory test delivery, so as to provide reference for more standardized and effective testing delivery for hospitals.

Direct-to-Consumer Genetic Testing: A Comprehensive Review.

Emerged in the early 2000s, direct-to-consumer (DTC) genetic testing has helped consumers access and understand their genetic information without the involvement of a healthcare provider. Unlike traditional clinical-based testing, in which a healthcare provider is responsible for ordering, testing, interpreting, and communicating the results, DTC testing provides valuable insights directly to individuals about their genetic information. It empowers consumers and their families to be proactive about their health and lifestyle. The online testing format has become increasingly popular due to its accessibility and affordability. However, it raises concerns about the accuracy and reliability of the results, data security and how to ensure privacy for consumers and regulators. A hybrid model combining elements from both DTC and clinical-based genetic testing has surfaced in the market recently. In the US, current health-related DTC genetic tests are not recognized for diagnostic purposes; instead, these tests are intended to provide genetic information that is associated with certain conditions, which may encourage consumers to take the opportunity to discuss the results and their implications with a healthcare provider. This DTC genetic testing review focuses on the fundamental concepts, applications, benefits, limitations, risks, and consumer concerns, as well as the state of the DTC framework compared with the clinical-based and hybrid models. Additionally, the regulatory oversight, data protection, and healthcare professional perspective on DTC genetic testing in the US will be discussed, including current policies and regulations.

The Single Leg Bridge Test does not replace handheld dynamometer hamstring tests in a clinical setting.

OBJECTIVE: To examine the correlation of Single Leg Bridge Test (SLBT) scores with maximum isometric strength values obtained in handheld dynamometer (HHD) hamstring tests performed in a clinical setting. DESIGN: Cross-sectional study. SETTING: Physical therapy clinic. PARTICIPANTS: Fifty healthy and physically active men. MAIN OUTCOME MEASURES: Correlation between SLBT scores and force values found in three HHD hamstring tests: test 'A', volunteer in prone with hip in neutral position and the knee flexed at ∼90°; test 'B', volunteer in supine with hip and knee flexed at ∼90°; and test 'C', volunteer in the same position used to perform the SLBT. RESULTS: The volunteers' SLBT score was 27.55 ± 7.81 repetitions. The SLBT scores were poorly associated with mean (r = 0.246) and peak (r = 0.321) results provided by HHD test 'A'. There were no significant correlations between the SLBT scores and mean or peak values obtained in tests 'B' and 'C' (p > 0.05). Similarly, the SLBT between-limb asymmetry was not associated with asymmetries found in HHD hamstring tests (p > 0.05). CONCLUSIONS: HHD hamstring tests should not be replaced by the SLBT. We recommend for clinicians to applying such tests in a complementary way to assess the hamstring's functional status.

Development and Application of a Stability Index Estimation Algorithm Based on Machine Learning for Elderly Balance Ability Diagnosis in Daily Life.

BACKGROUND: The stability index estimation algorithm was derived and applied to develop and implement a balance ability diagnosis system that can be used in daily life. METHODS: The system integrated an approach based on sensory function interaction, called the clinical test of sensory interaction with balance. A capacitance and resistance sensing type force mat was fabricated, and a stability index prediction algorithm was developed and applied using the center of pressure variables. The stability index prediction algorithm derived a center of pressure variable for 103 elderly people by Nintendo Wii Balance Board to predict the stability index of the balance system (Biodex SD), and the accuracy of this approach was confirmed. RESULTS: As a result of testing with the test set, the linear regression model confirmed that the r-value ranged between 0.943 and 0.983. To confirm the similarity between the WBB and the flexible force mat, each measured center of pressure value was inputted and calculated in the developed regression model, and the result of the correlation coefficient validation confirmed an r-value of 0.96. CONCLUSION: The system developed in this study will be applicable to daily life in the home in the form of a floor mat.

Objective Assessment of Syndesmosis Stability Using the Hook Test.

The hook test is a widely used intraoperative method for assessing syndesmosis stability. However, there are no recommendations regarding the force required to perform this test. Furthermore, the reliability of the test is unclear. Ten experienced surgeons performed hook tests on a cadaver bone model. The applied forces were recorded in a blinded manner. In addition, standardized hook tests with defined forces (50, 80, and 100 N) were performed on 10 pairs of cadaver lower legs and the syndesmosis was sequentially destabilized. Diastasis of the syndesmosis was recorded using an optical 3D camera system. A median force of 81 N (Range: 50 N-145 N) was applied. A proportion of 82% of the tests showed a force < 100 N. The data showed good intraraterreliability and poor interraterreliability. In the standardized investigation of the hook test on the cadaver bone model, both the force and the instability of the syndesmosis had a significant influence on the syndesmosis diastasis. Nevertheless, even with maximum instability of the syndesmosis, diastasis > 2 mm could only be measured in 12 of the 19 evaluable specimens. The widely used hook test shows a high variability when performed in practice. Even in a standardized manner, the hook test cannot detect a relevant syndesmosis injury.

Metabolic biomarkers significantly enhance the prediction of HBV-related ACLF occurrence and outcomes.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for patients with ACLF, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognostication. METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from patients with HBV-related chronic liver disease with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set. RESULTS: ACLF significantly altered the plasma metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of 90-day mortality in patients with ACLF (area under the curve 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (area under the curve 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography-mass spectrometry. CONCLUSIONS: Based on novel metabolite biomarkers, we established tests for HBV-related ACLF with higher accuracy than existing methods. CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872. IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality affecting 25% of patients hospitalized with cirrhosis. Chronic hepatitis B is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognostication are critical for improving clinical outcomes in patients with ACLF. Based on novel metabolite biomarkers, we developed liquid chromatography-mass spectrometry tests with improved accuracy for the early diagnosis and prognostication of HBV-related ACLF. The liquid chromatography-mass spectrometry tests can be implemented in clinical labs and used by physicians to triage patients with HBV-related ACLF to ensure optimized clinical management.

Physical Examination of Ankle Sprain and Ankle Instability: Can We Really Divide It into Low and High Ankle Sprains?

Lateral ankle ligament sprains and syndesmotic injuries are two different entities. However, they may be combined under the same spectrum depending on the arch of violence during the injury. Currently, the clinical examination has a limited value in the differential diagnosis between an acute anterior talofibular ligament rupture and a syndesmotic high ankle sprain. However, its use is indispensable for raising a high index of suspicion for detecting these injuries. Based on the mechanism of injury, clinical examination plays an essential role in guiding further imaging and early diagnosis of low/high ankle instability.

Preanalytic and Analytic Quality System Considerations in Noncoding RNA Biomarker Development for Clinical Diagnostics.

A frequent topic of biomedical research is the potential clinical use of non-coding (nc) RNAs as quantitative biomarkers for a broad spectrum of health and disease. However, ncRNA analyses have not been pressed into widespread diagnostic use. Strong preclinical evidence suggests obstacles in the translation and reproducibility of this type of biomarker which may result from preanalytical and analytical variation in the non-standardized processes used to collect, process, and store samples, as well as the substantive differences between small and long ncRNA. We performed a narrative review of selected literature, through the lens of key laboratory-developed test (LDT) regulations under the Clinical Laboratory Improvement Amendments (CLIA) in the United States, to study critical gaps in ncRNA validation studies. This review describes the leading candidate ncRNA subclasses, their biogenesis and cellular function, and identifies specific pre-analytical variables with disproportionate impact on testing performance. We summarize these findings with strategic recommendations to clinicians and biomedical scientists involved in the design, conduct, and translation of ncRNA biomarker development.

Optimal Identification of Muscle Synergies From Typical Sit-to-Stand Clinical Tests.

Goal: The goal of this manuscript is to investigate the optimal methods for extracting muscle synergies from a sit-to-stand test; in particular, the performance in identifying the modular structures from signals of different length is characterized. Methods: Surface electromyography signals have been recorded from instrumented sit-to-stand trials. Muscle synergies have then been extracted from signals of different duration (i.e. 5 times sit to stand and 30 seconds sit to stand) from different portions of a complete sit-to-stand-to-sit cycle. Performance have then been characterized using cross-validation procedures. Moreover, an optimal method based on a modified Akaike Information Criterion measure is applied on the signal for selecting the correct number of synergies from each trial. Results: Results show that it is possible to identify correctly muscle synergies from relatively short signals in a sit-to-stand experiment. Moreover, the information about motor control structures is identified with a higher consistency when only the sit-to-stand phase of the complete cycle is considered. Conclusions: Defining a set of optimal methods for the extraction of muscle synergies from a clnical test such as the sit-to-stand is of key relevance to ensure the applicability of any synergy-related analysis in the clinical practice, without requiring knowledge of the technical signal processing methods and the underlying features of the signal.

Clinical tests accuracy in diagnosing subacromial impingement syndrome: A systematic review.

OBJECTIVE: To determine the sensitivity and specificity of the clinical diagnostic tests of subacromial impingement syndrome. METHODS: The systematic review comprised search on PubMed, PEDro, Cochrane Library and Google Scholar databases. For prospective cohort studies published in peer-reviewed English-language journals without any time limit, at least fully describing one clinical test. Only studies with free full text available were included. Data extracted included sensitivity and specificity for each clinical test, and variations were sorted out by the 3 reviewers by discussion. RESULTS: Of the 4137 studies identified, 2951(71.3%) were on PubMed, 119(2.9%) PEDro, 5(0.1%) Cochrane Library and 1062(25.7%) Google Scholar. After screening out all the studies that did not match the detailed inclusion criterion, 3(0.07%) studies were selected for review; 1(33.3%) each done in Spain, Turkey and France. Overall, there were 181 aged 15-82 years; 85(47%) males and 96(53%) females. Supraspinatus palpation test had a sensitivity of 92%, while the modified Neer test had specificity of 95.56% in terms of ruling out subacromial impingement syndrome. CONCLUSIONS: Supraspinatus palpation and modified Neer tests were found to be the most effective in the diagnosis of subacromial impingement syndrome.

Impact of VALID Act implementation on mass spectrometry-based clinical proteomic laboratory developed tests.

Mass spectrometry (MS)-based clinical proteomic Laboratory Developed Tests (LDTs) for the measurement of protein biomarkers related to endocrinology, cardiovascular disease, cancer, and Alzheimer's disease are gaining traction in clinical laboratories due to their value in supporting diagnostic and treatment decisions for patients. Under the current regulatory landscape, MS-based clinical proteomic LDTs are regulated by Clinical Laboratory Improvement Amendments (CLIA) under the auspices of the Centers for Medicaid and Medicare Services (CMS). However, should the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act pass, it will grant the FDA greater authority to oversee diagnostic tests, including LDTs. This could impede clinical laboratories' ability to develop new MS-based proteomic LDTs to support existing and emerging patient care needs. Therefore, this review discusses the currently available MS-based proteomic LDTs and their current regulatory landscape in the context of the potential impacts imposed by the passage of the VALID Act.

Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition.

Blood contains a great deal of health-related information and can be used to monitor human health status. Clinically, venous or fingertip blood is usually used for blood tests. However, the clinical application settings of the two sources of blood are unclear. In this study, the proteomes of pairwise venous plasma (VP) and fingertip plasma (FP) were analyzed, and the levels of 3797 proteins were compared between VP and FP. The Spearman's correlation coefficient for the relationship between protein levels of VP and FP ranges from 0.64 to 0.78 (p < 0.0001). The common pathways of VP and FP are related to cell-cell adhesion, protein stabilization, innate immune response, and complement activation, the classical pathway. The VP-overrepresented pathway is related to actin filament organization, while the FP-overrepresented pathway is related to the hydrogen peroxide catabolic process. ADAMTSL4, ADIPOQ, HIBADH, and XPO5 both in VP and FP are potential gender-related proteins. Notably, the VP proteome has a higher interpretation on age than the FP proteome, and CD14 is a potential age-related protein in VP but not in FP. Our study mapped the different proteomes between VP and FP, which can provide value for the standardization of clinical blood tests.

Protocol to establish auxiliary diagnostic model for knee osteoarthritis functional testing equipment.

In China, 50% of Knee Osteoarthritis (KOA) patients will be treated with Traditional Chinese Medicine or a combination of Traditional Chinese and Western Medicine, which call for objective efficacy evaluation methods. The collection, processing and fusion of multi-source data were taken as the main methods, with 150 KOA patients and 100 healthy people as an example to design prospective clinical tests. Data were collected with tongue inspection APP, infrared instrument and channel instrument, etc. And the analysis, screening, fusion and modelling of multi-source data were conducted. The traditional clinical tests have been combined with the customized information platform in this study, which is convenient for clinical tests, medical follow-ups and timely feedback to statistical analysis of data.