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BACKGROUND Suboptimal endometrial receptivity is a key factor behind in vitro fertilisation (IVF) implantation failure. Direct clinical tests of the endometrium of natural killer (NK) cells and endometrial receptivity analysis (ERA) are controversial. AIMS To examine the current practice of endometrial receptivity tests (NK cells and ERA) and immunological treatments (corticosteroids, anticoagulants, antiplatelets, intravenous immunoglobulin, Intralipid, other) among fertility specialists in Australia and New Zealand. METHODS A prospective 23-item web-based survey was distributed by email via the Fertility Society of Australia and New Zealand, between August and October 2020. Data were collected and analysed using Qualtrics. RESULTS Of 238 fertility specialists, 90 completed the survey (response rate 37.8%). ERA (48/90, 53.3%) was most commonly ordered, followed by uterine NK (uNK) (36/90, 40.0%) and peripheral blood NK (pNK) (12/90, 13.3%). For all tests, the most common indication was recurrent implantation failure (RIF) (41/48, 22/36, 6/12; 85.4%, 61.1%, and 50.0%, respectively for ERA, uNK and pNK). Of those that did not offer these tests, the main reason cited was insufficient evidence (30/42, 47/54, 68/78; 71.4%, 87.0%, and 87.0%). A third of specialists offered empirical immunological treatment for RIF (30/90, 33.3%): anticoagulants (28/30, 93.3%), antiplatelets (27/30, 90.0%), and corticosteroids (25/30; 83.3%). The majority of specialists (56/90, 62.2%) stated they had refused a patient request for endometrial testing or treatment. CONCLUSIONS Tests for presumed endometrial receptivity pathology are often used in Australia and New Zealand. Immunological treatments for RIF are commonly employed empirically, without strong evidence of their effectiveness or safety. Further studies should focus on education and clinical adherence to evidence-based guidelines.

Rotator cuff tear is a leading cause of shoulder pain resulting in varying degree of disability to perform activities of daily living. A methodical history taking and focussed clinical examination helps in establishing the clinical diagnosis. A number of tests are mentioned in the literature to test the integrity of rotator cuff. This narrative review will focus upon methodology of each test, and their diagnostic accuracy. Keywords: Rotator cuff tear; Impingement; Clinical tests; Diagnosis.

Purpose Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD), assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease. Methods The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science in August 2020. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix. Results 105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies. Conclusions This is the first systematic review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time, resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features of the condition that develop in patients.

The development of fast and accurate screening tools, which could facilitate testing and prevent more costly clinical tests, is key to the current pandemic of COVID-19. In this context, some initial work shows promise in detecting diagnostic signals of COVID-19 from audio sounds. In this paper, we propose a voice-based framework to automatically detect individuals who have tested positive for COVID-19. We evaluate the performance of the proposed framework on a subset of data crowdsourced from our app, containing 828 samples from 343 participants. By combining voice signals and reported symptoms, an AUC of $0.79$ has been attained, with a sensitivity of $0.68$ and a specificity of $0.82$. We hope that this study opens the door to rapid, low-cost, and convenient pre-screening tools to automatically detect the disease., 5 pages, 3 figures, 2 tables, Accepted for publication at ICASSP 2021

Inflammatory biomarkers are closely related to infectious diseases. However, traditional clinical tests of laboratory inspection are unable to achieve rapid and accurate detection of these biomarkers on-site due to shortcomings such as complex experimental operation, expensive equipment, and long test time. Herein, we proposed a lateral flow assay (LFA) strip based on surface-enhanced Raman scattering (SERS) nanotags (SERS-LFA strips) for the simultaneous and quantitative detection of dual infection biomarkers, serum amyloid A (SAA) and C-reactive protein (CRP), respectively. In practice, mesoporous silica (mSiO2)-coated Au nanoparticles (Au NPs) were used as the SERS substrate. Mercaptobenzoic acid (MBA) was embedded in the internal gap between Au NPs and the mSiO2 shell to prepare AuMBA@mSiO2 NPs, onto which SAA and CRP antibodies were modified to prepare two AuMBA@mSiO2 SERS nanotags. The Raman intensities of the test and control lines were simultaneously identified for the qualitative detection of SAA and CRP, with limits of detection (LODs) as low as 0.1 and 0.05 ng/mL for SAA and CRP, respectively. Finally, aiming at point-of-care testing (POCT) applications, we used a smartphone-based portable Raman spectrometer to quantitatively analyze the SERS-LFA strips. The Raman signal could still be accurately detected when the concentration of SAA and CRP was 10 ng/mL, which is lower than the LOD required in clinical practice for most diseases. Therefore, taking into account its simple operation and short analysis time, by using a portable Raman spectrometer which can be equipped with a 5G cloud-based healthcare management system, the current strategy based on SERS-LFA provides the potential for the quick and on-site diagnosis of infectious diseases such as sepsis, which is of great significance for medical guidance on the treatment of widely spread infection-related diseases in remote areas that lack well-developed medical resources.

Background: Previous systematic reviews and meta-analyses on the diagnostic accuracy of shoulder clinical tests do not reach conclusions regarding subscapularis tears. Purpose: To compare the diagnostic accuracy of commonly used clinical tests for subscapularis tears. Study Design: Systematic review; Level of evidence, 3. Methods: An electronic literature search was conducted using Medline, Embase, and the Cochrane Library/Central. Eligibility criteria were original clinical studies reporting the diagnostic accuracy of clinical tests to diagnose the presence of rotator cuff tears involving the subscapularis. Results: The electronic literature search returned 2212 records, of which 13 articles were eligible. Among 8 tests included in the systematic review, the lift-off test was most frequently reported (12 studies). Four tests were eligible for meta-analysis: bear-hug test, belly-press test, internal rotation lag sign (IRLS), and lift-off test. The highest pooled sensitivity was 0.55 (95% CI, 0.28-0.79) for the bear-hug test, while the lowest pooled sensitivity was 0.32 (95% CI, 0.13-0.61), for the IRLS. In all tests, pooled specificity was >0.90. Conclusion: Among the 4 clinical tests eligible for meta-analysis (bear-hug test, belly-press test, IRLS, and lift-off test), all had pooled specificity >0.90 but pooled sensitivity Registration: PROSPERO (CRD42019137019).

Parkinson's disease is a brain-related disease that is common in every person mainly persons above age 45 years. This disease causes numbness in muscles, swallowing problems, bending of the back, shivering in hands, smell dysfunction, speaking problem, Hearing problem, and many more. Parkinson's disease has to be diagnosed as early as possible since the clinical tests, which take hours to detect, may cost a loss of time and money. An automated model for detecting Parkinson's disease in a person with greater accuracy is proposed in this paper. While several models for detecting Parkinson's disease have been established, they are all less reliable and precise. Our model is created using the gradient boosted decision tree, which not only reliably predicts Parkinson's disease in a human, but also predicts it quickly. The feature set contains 22 parameters of the voice signal, which are given to the XGBoost classifier. The developed model predicts Parkinson's disease with 96.6% of accuracy, 95.6% of sensitivity, 100% of specificity, 100% of Precision, F-Score 97.7%.

Purpose: Implementation of the International Consortium for Health Outcomes Measurements (ICHOM) standard for cataract surgery into clinical practice at an Italian tertiary referral centre. Methods: Prospective, observational, descriptive study consisting of the registry and analysis of cataract surgeries performed during a 6-month enrolment period at the University Eye Clinic of Trieste, Trieste, Italy. Outcomes were recorded and analysed according to the ICHOM Cataract Standard Set version 2.0.1. Records included clinician-reported outcome measures (CROMs) – visual outcome and complications – and patient-reported outcome measures (PROMs) – self-assessed vision with the Catquest-9SF questionnaire. Correlations between PROMs and CROMs were evaluated. A multiple linear regression was used for predicting the change in PROMs with surgery. Results: A total of 218 eyes (of 218 patients) were analysed. Postoperative corrected distance visual acuity (CDVA) was ⩾0.3 in 89.0% (194/218) of eyes. There was a statistically significant improvement of the post-operative Catquest-9SF global average score. ( p 2: 0.527) based on preoperative Catquest-9SF total score, presence or not of macular degeneration, presence or not of intraoperative complications, age >75 years old, and preoperative CDVA. Conclusions: Cataract surgery improves the functional vision, with some factors limiting the outcomes such as comorbidities. Self-perceived improvement in intermediate vision significantly influenced the improvement in self-assessed vision.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers, and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the rapid progress in basic research and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.

Purpose The purpose of this study was to describe the face mask (FM)-related ocular surface changes using clinical tests, in vivo confocal microscopy (IVCM) and impression cytology (IC), and to investigate the Dry Eye-related Quality of life Score (DEQS). Methods Sixty-six patients with dry eye disease (DED) and 62 healthy subjects (group 2) using FM were enrolled. Groups were divided into: groups 1A and 2A: < 3 hours of FM wear; groups 1B and 2B: 3 to 6 hours; and groups 1C and 2C: > 6 hours. Patients underwent DEQS questionnaire, break-up time (BUT), Schirmer test I (STI), fluorescein and lissamine staining (FS and LS), IVCM to determine corneal dendritic cell density (DCD) and goblet cell density (GCD), and IC to measure HLA-DR, at baseline and after 3 months. Results FM use duration before enrollment was 27 ± 2.3 and 30 ± 4.1 (days ± SD) for groups 1 and 2 (P > 0.05). After 3 months, DEQS worsened in groups 1B and 1C, STI in groups 1A to 1C, FS and LS in group 1C (P < 0.05); in controls, BUT and FS worsened only in group 2C (P < 0.05). DCD significantly increased in groups 1A to 1C and HLA-DR in groups 1B and 1C (P < 0.05), whereas GCD did not significantly change. DCD and HLA-DR increased only in group 2C (P < 0.05). DEQS significantly correlated with DCD (P = 0.05, r = 0.698; P < 0.001, r = 0.832) and HLA-DR (P = 0.043, r = −0.687; P < 0.001, r = 0.861) at baseline and 3 months. Conclusions Use of FM increases ocular surface inflammation and negatively impacts the quality of life in patients with DED. Translational Relevance The study of the prolonged use of FM effects may be relevant to managing DED.

Objectives: The aim of this review was to systematically review the cost-effective diagnostic utility of clinical tests to diagnose subacromial impingement syndrome. Data Sources: The following electronic databases: Medline, EMBASE, Science Direct and the Cochrane Library were searched in June 2020 to identify the studies that investigated the diagnostic accuracy of clinical tests to diagnose SAIS. The search was restricted to articles written in English. Study Selection: This study included diagnostic accuracy of cohort studies that directly compared the diagnostic utility of clinical tests for diagnosing SAIS against either surgical or indirect imaging reference standards. The PRISMA guidelines were followed to accomplish this review. Two reviewers independently performed the study’s methodological quality assessment by using the QUADAS tool. Data Extraction: The sensitivity and specificity for each clinical test waa extracted from the included studies and both positive and negative likelihood ratios were tabulated either direct from available studies or calculated from the provided sensitivity and specificity data. Data Synthesis: This review included 14 studies in total of 1756 shoulders and considered standard, modi?ed and novel clinical tests for making a differential diagnosis on SAIS. In this review, included studies’ overall methodological quality is high and there appears to be the diagnostic utility of the subacromial grinding test, lift-off, bear-hug and belly-off tests provide significant evidence to rule in SAIS when the tests are positive. Conclusion: This is an updated study of a previous systematic review on the diagnostic accuracy of clinical tests for SAIS. Making a precise differential diagnosis will ultimately ensure the appropriate therapeutic interventions, subsequently successful prognosis on SAIS patients thus, this review findings of diagnostic utility clinical tests need to be considered in the context of clinical practice of the overall patient assessment.

Background Pompe Disease (PD) is a rare inherited metabolic myopathy, caused by lysosomal-α-glucosidase (GAA) deficiency, which leads to glycogen accumulation within the lysosomes, resulting in cellular and tissue damage. Due to the emergence of a disease modifying treatment with recombinant GAA there has been a large increase in studies of late onset Pompe Disease (LOPD) during the last decade. Methods The present study evaluates muscle quality in 10 patients with LOPD receiving treatment with enzyme replacement therapy and in 10 age and gender matched healthy controls applying T1-weighted Dixon MR imaging and isokinetic dynamometry. Muscle quality was determined by muscle strength in relation to muscle size (contractile cross-sectional area, CSA) and to muscle quality (fat fraction). A follow-up evaluation of the patients was performed after 8–12 months. Patient evaluations also included: six-minute walking test (6MWT), forced vital capacity, manual muscle testing and SF-36 questionnaire. Results Fat fraction of knee flexors (0.15 vs 0.07, p p r = 0.86, knee extensors: r = 0.88, hip extensors: r = 0.83, p

Submitted by RONALDO VALDIR BRIANI (ronaldo.briani@unesp.br) on 2021-05-29T11:31:44Z No. of bitstreams: 1 Tese completa.pdf: 2244578 bytes, checksum: ed7c287afef803e140f136b7f0873e17 (MD5) Rejected by Claudia Adriana Spindola null (claudia@fct.unesp.br), reason: Boa Tarde, Solicitamos que realize correções na submissão seguindo as orientações abaixo: - Segundo a estrutura do texto, após o Abstract e palavras-chave, inclui uma folha com a Lista de Tabelas. Agradecemos a compreensão. Qualquer dúvida entre em contato pelo e-mail bibaqu.fct@unesp.br 18 99760-1512 on 2021-06-01T21:22:29Z (GMT) Submitted by RONALDO VALDIR BRIANI (ronaldo.briani@unesp.br) on 2021-06-02T13:16:53Z No. of bitstreams: 1 Tese completa.pdf: 2712460 bytes, checksum: 25430d06f7030c70ca868e811745e26e (MD5) Approved for entry into archive by Claudia Adriana Spindola null (claudia@fct.unesp.br) on 2021-06-02T13:44:15Z (GMT) No. of bitstreams: 1 briani_rv_dr_prud.pdf: 2712460 bytes, checksum: 25430d06f7030c70ca868e811745e26e (MD5) Made available in DSpace on 2021-06-02T13:44:15Z (GMT). No. of bitstreams: 1 briani_rv_dr_prud.pdf: 2712460 bytes, checksum: 25430d06f7030c70ca868e811745e26e (MD5) Previous issue date: 2021-04-30 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) A dor femoropatelar (DFP) é caracterizada por dor na região anterior do joelho exacerbada por atividades que aumentam a sobrecarga da articulação femoropatelar. Um dos principais focos de estudos em DFP são os músculos extensores de joelho, extensores e abdutores de quadril. Apesar da importância comprovada desses grupamentos musculares na DFP, essa desordem tem característica multifatorial e outros grupos musculares também podem estar comprometidos. Achados de estudos prévios indicam que alterações na funcionalidade dos flexores de joelho e músculos do tronco (flexores laterais, anteriores e extensores) também podem estar associadas com a DFP, embora mais estudos sejam necessários para avançar o entendimento nessa temática. Além disso, o comprometimento da função dos músculos do tronco e flexores de joelho pode estar associado com alterações na mecânica articular durante tarefas funcionais devido à DFP. Para entender melhor a influência da DFP na mecânica articular do tronco e membro inferior, reduzindo limitações causadas pelo carácter intermitente da DFP e o desenho transversal da maioria dos estudos, investigar a influência da exacerbação da DFP nessas variáveis pode ser uma alternativa interessante. Nesse contexto, seis estudos originais que compõem esta tese foram realizados com o objetivo geral de investigar a relação da DFP com os músculos do tronco e flexores de joelho e a influência da exacerbação da DFP na mecânica articular do tronco e membro inferior. De forma geral, os achados desses estudos indicaram comprometimento na função muscular dos flexores de joelho e dos músculos do tronco, o que está relacionado com a dor ou função objetiva de indivíduos com DFP. Além disso, foram encontradas mudanças na mecânica articular do joelho e na coordenação de tronco durante tarefas funcionais após a exacerbação da DFP. Em conjunto, esses achados contribuem no entendimento da relação dos músculos do tronco e flexores de joelho com a DFP e como a sua exacerbação influencia a mecânica articular. Patellofemoral pain (PFP) is characterized by diffuse anterior knee pain exacerbated by activities that increase the load in the patellofemoral joint. One of the main focus of PFP research has been the knee extensors, hip abductors and extensors. Despite the evidenced importance of these muscle groups to PFP, this disorder has a multifactorial characteristic and other muscle groups may also be compromised. Findings from previous studies indicate that changes in the muscle capacity of the knee flexors and trunk muscles (lateral, anterior and extensor flexors) may also be associated with PFP, although further studies are needed to further understand this topic. In addition, impaired function of the trunk and knee flexor muscles may be associated with changes in joint mechanics during functional tasks due to PFP. To better understand the influence of PFP on trunk and lower limb mechanics, overcoming limitations caused by the intermittent nature of PFP and the cross-sectional design of most studies, investigating the influence of PFP exacerbation on these variables can be an interesting alternative. In this context, six original studies that compose this thesis were carried out with the general objective of investigating the relationship of PFP with trunk and knee flexor muscles and the influence of PFP exacerbation on trunk and lower limb mechanics. Overall, the findings of these studies indicated impairments in the muscle function of the knee flexors and trunk muscles, which were related to pain or objective function of individuals with PFP. In addition, changes in knee joint mechanics and trunk coordination were found during functional tasks after the exacerbation of DFP. Put together, these findings contribute to the understanding of the relationship between trunk and knee flexor muscles with PFP and how the exacerbation of PFP influences joint mechanics. FAPESP: 17/20483-7 CAPES: 001

Background Clinical tests should replicate the stressful positions encountered during sport participation. Evaluating the kinetic and electromyographical demands of clinical tests enables clinicians to choose appropriate tests for specific sports. Purpose To describe the shoulder forces and muscle activation levels during closed chain functional tests of Line Hops (LH) and Side Hold Rotation (SHR). Study Design Descriptive biomechanical study Methods Ten asymptomatic participants were examined in a university laboratory. Two functional tests were evaluated using three-dimensional video analysis and electromyography to measure shoulder forces, moments, and muscular activity levels. Results SHR produced a peak average posterior translation force of 4.84 N/kg (CI95 4.32-5.36N/kg) and a peak average anterior translational force of 1.57 N/kg (CI95 1.10-2.01N/kg). High levels of serratus anterior (98% maximum voluntary isometric contraction (MVIC) and infraspinatus (52 %MVIC) were recorded during SHR. LH produced a posterior translational force of 4.25 N/kg (CI95 3.44–5.06N/kg). High levels of serratus anterior (105 %MVIC) and infraspinatus (87 %MVIC) were recorded during the push off phase of this activity. Conclusions LH and SHR placed large posterior translational forces that approached half of a person’s bodyweight on shoulder structures. SHR produced an anterior translation force at extremes of horizontal abduction placing approximately 18% of bodyweight on shoulder structures. The LH test required the serratus anterior to provide power to push the upper torso of the ground while both the serratus and the infraspinatus provides scapular and humeral stability, respectively. Level of Evidence 4: Case series

Clinical examination has become an important method of disease diagnosis, curative effect evaluation, prognosis judgment and health monitoring, and the biological reference interval is the reference standard to interpret test results and analyses of test information. In clinical tests, the reference interval is often affected by race, sex, age, geographical location and growth and development, so it is very important to establish a suitable reference interval for each laboratory. It is a huge and arduous task for each laboratory to establish its own reference interval. It is unrealistic for different measurement systems to establish reference intervals. According to the C28-A3c guideline from the Clinical and Laboratory Standards Institute (CLSI), clinical laboratories can appropriately transfer the reference intervals provided by other laboratories. This paper reviews whether the biomarkers in multiregional laboratories can transfer reference intervals between different measurement systems to expand the application of reference interval databases and ensure the accuracy and consistency of the test results.

Recently, sound-based COVID-19 detection studies have shown great promise to achieve scalable and prompt digital pre-screening. However, there are still two unsolved issues hindering the practice. First, collected datasets for model training are often imbalanced, with a considerably smaller proportion of users tested positive, making it harder to learn representative and robust features. Second, deep learning models are generally overconfident in their predictions. Clinically, false predictions aggravate healthcare costs. Estimation of the uncertainty of screening would aid this. To handle these issues, we propose an ensemble framework where multiple deep learning models for sound-based COVID-19 detection are developed from different but balanced subsets from original data. As such, data are utilized more effectively compared to traditional up-sampling and down-sampling approaches: an AUC of 0.74 with a sensitivity of 0.68 and a specificity of 0.69 is achieved. Simultaneously, we estimate uncertainty from the disagreement across multiple models. It is shown that false predictions often yield higher uncertainty, enabling us to suggest the users with certainty higher than a threshold to repeat the audio test on their phones or to take clinical tests if digital diagnosis still fails. This study paves the way for a more robust sound-based COVID-19 automated screening system., Accepted by INTERSPEECH 2021

Purpose To propose a new method of identifying clusters in multifocal electrophysiology (multifocal electroretinogram: mfERG; multifocal visual-evoked potential: mfVEP) that conserve the maximum capacity to discriminate between patients and control subjects. Methods The theoretical framework proposed creates arbitrary N-size clusters of sectors. The capacity to discriminate between patients and control subjects is assessed by analysing the area under the receiver operator characteristic curve (AUC). As proof of concept, the method is validated using mfERG recordings taken from both eyes of control subjects (n = 6) and from patients with multiple sclerosis (n = 15). Results Considering the amplitude of wave P1 as the analysis parameter, the maximum value of AUC = 0.7042 is obtained with N = 9 sectors. Taking into account the AUC of the amplitudes and latencies of waves N1 and P1, the maximum value of the AUC = 0.6917 with N = 8 clustered sectors. The greatest discriminant capacity is obtained by analysing the latency of wave P1: AUC = 0.8854 with a cluster of N = 12 sectors. Conclusion This paper demonstrates the effectiveness of a method able to determine the arbitrary clustering of multifocal responses that possesses the greatest capacity to discriminate between control subjects and patients when applied to the visual field of mfERG or mfVEP recordings. The method may prove helpful in diagnosing any disease that is identifiable in patients’ mfERG or mfVEP recordings and is extensible to other clinical tests, such as optical coherence tomography., Agencia Estatal de Investigación

Microfluidics and 3D printing will allow a faster research and development in pharmaceutical and medical areas, supporting new solutions for active pharmaceutical production and clinical tests with...

Background Outcome prediction in comatose patients following cardiac arrest remains challenging. Here, we assess the predictive performance of electroencephalography-based power spectra within 24 h from coma onset. Methods We acquired electroencephalography (EEG) from comatose patients (n = 138) on the first day of coma in four hospital sites in Switzerland. Outcome was categorised as favourable or unfavourable based on the best state within three months. Data were split in training and test sets. We evaluated the predictive performance of EEG power spectra for long term outcome and its added value to standard clinical tests. Results Out of 138 patients, 80 had a favourable outcome. Power spectra comparison between favourable and unfavourable outcome in the training set yielded significant differences at 5.2–13.2 Hz and above 21 Hz. Outcome prediction based on power at 5.2–13.2 Hz was accurate in training and test sets. Overall, power spectra predicted patients’ outcome with maximum specificity and positive predictive value: 1.00 (95% with CI: 0.94–1.00 and 0.89–1.00, respectively). The combination of power spectra and reactivity yielded better accuracy and sensitivity (0.81, 95% CI: 0.71–0.89) than prediction based on power spectra alone. Conclusions On the first day of coma following cardiac arrest, low power spectra values around 10 Hz, typically linked to impaired cortico-thalamic structural connections, are highly specific of unfavourable outcome. Peaks in this frequency range can predict long-term outcome.

Practice effects have been observed among performance-based clinical tests administered to prosthesis-users. Their impact on test applications remains unknown.To determine whether scoring a clinical balance test using conventional procedures that do not accommodate practice effects reduces its diagnostic accuracy relative to scoring it using recommended procedures that do accommodate practice effects.Cross-sectional study.Narrowing Beam Walking Test data from 40 prosthesis users was scored using recommended methods (i.e. average of trials 3-5) and conventional methods applied to other tests (i.e. mean or best of trials 1-3). Area under the receiver operating characteristic curve for each method was compared to 0.50, to determine if it was better than chance at identifying prosthesis-users with a history of falls, and to 0.80, to determine if it surpassed a threshold recommended for diagnostic accuracy.Receiver operating characteristic curve area decreased when the Narrowing Beam Walking Test was scored using conventional rather than recommended procedures. Furthermore, when scored using conventional procedures, the NBWT no longer discriminated between prosthesis-users with and without a history of falls with a probability greater than chance, or exceeded recommended diagnostic thresholds.Scoring the Narrowing Beam Walking Test using conventional procedures that do not accommodate practice effects decreased its diagnostic accuracy among prosthesis-users relative to recommended procedures. Conventional scoring procedures may limit the effectiveness of performance-based tests used to screen for fall risk in prosthesis-users because they do not mitigate practice effects. The influence of practice effects on other tests, and test applications (e.g. clinical evaluation and prediction), is warranted.Scoring a clinical balance test using conventional procedures that do not mitigate practice effects reduced its diagnostic accuracy. Changing administration and scoring procedures to accommodate practice effects should be considered to improve the diagnostic accuracy of other performance-based balance tests.

Context:Altered diaphragm function is linked to decreased core stabilization, postural changes, and decreased function. Two clinical tests used to assess breathing are the Hi-lo and lateral rib expansion (LRE) tests. It is currently unknown how breathing classification based on these tests differ and how their results are affected by varying test positions.Objective:To compare the results of breathing tests when conducted in varying test positions.Design:Prospective cross-sectional study.Setting:University laboratory.Participants:A total of 50 healthy adults (females 31 and males 29; age 29.3 [4.1] y; height 170.0 [10.4] cm; weight70.7 [15.1] kg).Intervention(s):Hi-lo and LRE tests in supine, seated, standing, and half-kneeling body positions. All tests were recorded and later scored by a single examiner. A generalized estimating equations approach with breathing test and body position as factors was used for analysis. Pairwise comparison with Bonferroni correction was used to adjust for multiple tests. Statistical significance was set atP = .05, 2 tailed.Main Outcome Measures:Hi-lo and LRE tests were scored based on the presence or absence of abdominal excursion, LRE, and superior rib cage migration. Following scoring, results were classified as functional or dysfunctional based on observation of these criteria.Results:A significant breathing test × test position interaction (P P P P P = .52). In the LRE test, all positions were similar (P > .99) except for half-kneeling, which was significantly different from all other positions (P Conclusions:The Hi-lo test and LRE tests assess different breathing mechanics. Clinicians should use these tests in combination to gain a comprehensive understanding of a person’s breathing pattern. The Hi-lo test should be administered in multiple testing positions.

The design and functional capabilities of the portable device for laser-and-ultrasound therapy BINOM®-FIZIO LUZT are described together with the experience of its use for treating patients with chronic obstructive lung disease (COLD). Infrared laser pulses and ultrasound generated by an array of sources are the therapeutic agents used for treatment. The developed device makes it possible to implement a new physical therapy technique for simultaneous (concomitant) treatment with low-intensity laser radiation and ultrasound. Clinical tests showed the device to be cost-effective and improve the clinical effect of combination treatment. It allows better expectoration, peripheral blood parameters, and respiratory function to be achieved.

Objective To assess the risk of developing atherosclerotic cardiovascular disease (ASCVD) in Pakistani population. Methodology This cross-sectional study includes 9885 subjects with ASCVD risk. Baseline demographic characteristics were obtained by using predesigned questionnaire. Clinical tests were analyzed by collecting fasting blood sample. Risk calculator application (Software) developed by ACC/AHA used to score the risk of ASCVD. Risk score with age group Results Mean age of subjects was 49.42±10.58 years. Significant difference for basic demographic and clinical characteristics (p Conclusion Our findings are comparable as per the reported international data highlighting that history of current smoking, high cholesterol, type 2 diabetes and hypertension are considered as a major potential underlying risk factors for ASCVD in Pakistani individuals.

The expanding CRISPR-Cas9 technology is an easily accessible, programmable, and precise gene-editing tool with numerous applications, most notably in biomedical research. Together with advancements in genome and transcriptome sequencing in the era of metadata, genomic engineering with CRISPR-Cas9 meets the developmental requirements of precision medicine, and clinical tests using CRISPR-Cas9 are now possible. This review summarizes developments and established preclinical applications of CRISPR-Cas9 technology, along with its current challenges, and highlights future applications in translational research. Keywords: CRISPR-Cas9, gene editing, off-target, gene therapy, tumor immunotherapy

Linburg–Comstock variation, the tendinous interconnection between flexor pollicis longus and flexor digitorum profundus, is known to have a wide frequency range. Its prevalence is reported with a range of 13–66%. The aim of the study was to assess this variation in general population and to correlate it with gender and side. This prospective study included 215 subjects (82 males and 133 females). Two clinical tests were conducted to diagnose the variation and to detect any related symptomatology. The primary outcome was set to be the prevalence of Linburg–Comstock variation. Secondary outcomes were defined as gender-based prevalence, side-based prevalence, and Linburg–Comstock variation prevalence association with gender and side. Linburg–Comstock variation was clinically diagnosed in 130 (60.47%) participants. Unilateral and bilateral prevalence were of 17.21% and 43.26%, respectively, yielding a statistically significant difference. Right-sided and left-sided presence were calculated at 7.44% and 9.77%. Bilateral prevalence was statistically more common in females. Right-sided variation was found to be more frequent in males while left-sided variation was more prevalent in females. The index finger was the most commonly involved with prevalence of 91.03%. Symmetry was noted in 67.74% of subjects. The results of our study demonstrated a relatively high prevalence of the Linburg–Comstock variation in Serbian population. We noted a few unusual cases and this finding point to the existence of the broader spectrum of Linburg–Comstock variation, and complexity of the flexor apparatus of the hand, so, further investigations about this topic are needed to improve our knowledge. Due to the possibility of false-positive result during clinical testing we suggest to use expanded clinical method.

BackgroundTear film stability is important for healthy visual function, and yet little is known of the ageing mechanisms. The aim of this study was to investigate parallels between biochemical changes and clinical physical parameters, which occur in the tear film of two subject populations differing in age by over 30 years.MethodsTwo distinct age groups were chosen: 11 ‘younger’ (23.7±2.1 years) and 19 ‘older’ (63.0±4.0 years) subjects. A series of clinical tests were performed to access tear volume, tear film stability and general ocular health. Tear protein analyses from extracted Schirmer strips were conducted with the Agilent 2100 Bioanalyzer.ResultsClinical investigations highlighted significant differences between the age groups. For example: McMonnies scores (p=0.009) and bulbar redness (p=0.038) were higher for the older group, whereas tear meniscus height was larger (p=0.018) in the younger group. Similarly, relative plasma-derived albumin levels were higher (17.1%±12.4%) in the tears of the older, compared with the younger (5.0%±9.6%) group. A protein peak at ∼23 kDa was observed in 53% of the older group samples but in only 36% of the samples of the younger subjects (p=0.122).ConclusionsDistinct differences in tear film composition between the two age groups were observed. Parallels in terms of clinical symptoms which reflected a biochemical response (and vice versa) were found, but specific correlations between clinical measurements and biomarkers for individual subjects were not observed.

International audience; OBJECTIVE:Pregnancy-related changes in ligament laxity have been shown to be associated with various disorders such as back pain or pelvic floor disorders. The purpose of this study was to assess laxity changes during pregnancy by confronting different methods in order to suggest a simple clinical tool helping to prevent the aforementioned problems.DESIGN:Seventeen pregnant women were evaluated at the first, second and third trimesters as cases and 16 non-pregnant women participated as controls. Ligamentous laxity was measured using an extensometer for the metacarpophalangeal joint of the index, a fingertip to floor test and a sit and reach test to assess hip and lumbar flexibility and the Beighton score. Statistical analysis included independent samples t-tests, analysis of variance and Pearson correlation coefficients.RESULTS:Laxity of the metacarpophalangeal joint increased by 11% from the first to the second trimester of pregnancy and stabilized until delivery. The Beighton score was significantly higher in the second trimester of pregnancy (p

Salivary urea was reported to be a useful biomarker to reflect the blood urea nitrogen in chronic kidney disease patients. However, as a new biomarker, enormous clinical trials are required to define the intended-use and to verify the specification. In this report, we demonstrated a low-cost easy-operated real-time sensing system (optical fiber-urea-sensing, OFUS, system) to detect salivary urea. We aim to make the system easily reproduced by the community to stimulate abundant clinical tests worldwide. The OFUS system is composed of a simple three-dimensional printed tank to link with two optical fibers, one connecting with a commercial light-emitting diode to deliver the input light signal, the other connecting with a commercial cadmium sulfide photo-conductive cell to detect the sensing signal. To allow on-site detection without any sample pretreatment, only 1 μl saliva is needed to be mixed with 10 μl urease solution and 90 μl pH indicator solution in the reaction tank and the detection time is only 20 s. A stable and reproducible calibration curve can be easily built with a detection range as 24–300 mg/dL. The OFUS system successfully detected saliva with added synthetic urea and samples from chronic kidney disease patients. A good agreement between the OFUS system and the commercial kit was obtained. A good correlation between salivary urea and the blood urea nitrogen was also confirmed.

The function of pulmonary allografts is regularly impaired by alloimmune reactions with quite variable clinical outcomes, different involved effector cells and molecules, as well as affected anatomical compartments. Acute rejection of grafts after lung transplantation (LuTx) is not only associated with the subsequent development of acute graft dysfunction, but can also contribute - among other immunological and nonimmunological factors - to the development of chronic lung allograft dysfunction (CLAD), which is the main reason for the limited long-term survival after LuTx. In addition to ACR and analogous to other solid organ transplants, the importance of antibody-mediated (humoral) rejection (AMR) in LuTx has also been recognized. There are currently no specific laboratory, radiological, or clinical tests available for either ACR or AMR. Only by the synoptic examination of histopathological changes and interpretation against the background of microbiological, virological, serological, and functional findings, can adequate sensitivity and specificity be achieved in the diagnostics of rejection. In this article, the current criteria for histopathological diagnostics of rejection following LuTx are summarized and the most important differential diagnoses are discussed.

Purpose: To investigate to what extent the OSDI can be utilized as a discriminative test for clinical findings. Methods: One thousand and ninety patients with dry eye disease (DED) were consecutively included and examined for osmolarity, tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), meibum quality (MQ), and diagnosis of meibomian gland dysfunction (MGD). Receiver-operating characteristic curve (ROC) analysis considering optimum balanced sensitivity and specificity (close to 50%) was used for assessment. Results: The present study on more than 1,000 patients indicates that the OSDI in the ROC curve analysis is a poor discriminator of pathological scores for TFBUT ≤ 5 (AUC = 0.553; p = .012) and ≤10 s (AUC = 0.608; p = .002), OSS ≥ 3 (AUC = 0.54; p = .043), ST ≤ 5 (AUC = 0.550; p = .032) and ≤10 mm/5 min (AUC = 0.544; p = .016), and ME ≥ 1 (AUC = 0.594; p = 308 and >316 mOsm/L, OPI, OSS > 1, MQ, and MGD could not be discriminated by OSDI (p > .05). Conclusion: Cut-off values for the OSDI can be defined to discriminate pathological TFBUT (≤5 and ≤10), OSS (≥3), ST (≤5 and ≤10) and ME, however, the discriminability was low. Our comprehensive study emphasises the importance of taking both symptoms and signs into account in DED management.

International audience; The aim of this study was to explore the relationships between physical performance variables and bone parameters such as bone mineral density (BMD), bone mineral content, hip geometry indices, and trabecular bone score in a group of young overweight and obese adult women. Sixty-eight overweight/obese (body mass index ≥25 kg/m; 25.5-42.4 kg/m) young women whose ages range from 18 to 35 yr participated in this study. Body composition and bone outcomes were measured by dual-energy X-ray absorptiometry. Maximum oxygen consumption (VO max, in liter per minute) was determined indirectly using a progressive shuttle run test. One-repetition-maximum half-squat was directly measured. Vertical jump was measured and maximum power (P max) of the lower limbs was calculated. Lean mass was positively correlated to whole body (WB) BMD, total hip BMD, femoral neck (FN) BMD, femoral neck cross-sectional area (FN CSA) and femoral neck cross sectional moment of inertia (FN CSMI) (p < 0.05). VO max (in liter per minute) and muscle power were positively correlated to WB BMD, total hip BMD, FN BMD, FN CSA, and FN CSMI (p < 0.05). One-repetition-maximum half-squat was positively correlated with lumbar spine trabecular bone score, WB BMD, FN BMD, FN CSA and FN CSMI (p < 0.05). This study suggests that lean mass, vertical jump, VO max (liter per minute), muscle power and one-repetition-maximum half squat are positive determinants of BMD and hip geometry indices in young overweight and obese women.

BACKGROUND: Hamstring tightness is a common condition typically assessed via the active knee extension (AKE), passive straight leg raise (PSLR), V-sit and reach (VSR), and finger-floor-distance (FFD). PURPOSE: The purpose of this study was to investigate the relationships between four common clinical tests of apparent hamstring tightness. A secondary purpose was to compare the differences in correlations between sub-groups based on positive test findings. STUDY DESIGN: Descriptive, correlational laboratory design. METHODS: Recreationally active individuals (N = 81; 23.7 ± 5.9 years) performed the AKE, PSLR, VSR, and FFD in a randomized order, and subsequent correlational analyses were conducted. RESULTS: Strong correlations were identified between the VSR and FFD (r = -.798, r(2) = .637, p

Background: The meniscus of the knee are vital for load bearing and shock absorption. Meniscal injury are common in young active adults who engaged in athletic activities. Following meniscal injury the presentation may vary from mild joint discomfort to frank locking of the joint. This creates a lot of morbidity to the patient. Various clinical tests are available for examining the integrity of the meniscus. The Thessaly test and McMurray test are very useful and cheap screening tools for identifying patient with suspected meniscal injuries. Before advising any patient presenting with traumatic knee pain for expensive investigations like MRI for suspected meniscus injury, these two clinical tests can serve as useful adjuncts in the management of such patients as not all meniscus tear need invasive treatment.Objectives: To assess the validity of a new clinical test (Thessaly) as a means of diagnosing meniscal tears of the knee by comparing the findings of Thessaly test with those of MRI and /or arthroscopy.Materials and Methods: This cross-sectional study was done between June 2016 to June 2017 at chettinad hospital & research institute on consecutive patients who presented with suspected meniscal injury. These patients were screened for meniscal injuries by performing the McMurray and Thessaly test. Patients with strong clinical suspicion for meniscal tear were then advised MRI of the injured knee. The findings of MRI were then correlated with the clinical findings to measure the diagnostic accuracy.Results: A total of 71 patients were included in the study. The mean of age was 29.77 years with a standard deviation of 7.8. Injury during sports activity accounting for 56.34% of the study sample was the most common mode of injury. The McMurray test was positive in 66.20% and Negative in 33.80% of the study population. The Thessaly test at 5 degree of knee flexion was positive in 63.38% and Negative in 36.62% of the study population. The Thessaly test at 20 degrees of knee flexion was positive in 73.24% and Negative in 26.76% of the study population. Thessaly test in 20 degree flexion is more sensitive than McMurray test for diagnosis of meniscal lesions. Whereas McMurray test has better specificity and better predictive values compared to Thessaly test. Conclusions: Both McMurray test and Thessaly test either singly or combined cannot be used as an alternative to MRI in confirming the diagnosis of meniscal lesions. However, they can be used as an effective screening tool in the identification of patients with meniscal lesions who may benefit from further investigations like MRI.

Impaired motor control post-stroke is typically measured using clinical assessments employing categorical and subjective scoring. We investigated quantitative kinematic parameters of a complex movement with therapy in chronic stroke. Tri-axial accelerometry of the more-affected arm of 24 patients was recorded during early- (day 2-3) and late- (days 12-14) therapy, and for 13 patients at 6-month follow-up. Clinical assessments included the classification of motor-function as low, moderate, or high. Kinematic parameters were measured during Wii-baseball swings to assess the effect of time and the level of motor-function. Clinical tests improved over time (all p

Background: There is limited information about the agreement and reliability of clinical shoulder tests. Objectives: To assess the interrater agreement and reliability of clinical shoulder tests in patients with shoulder pain treated in primary care. Methods: Patients with a primary report of shoulder pain underwent a set of 21 clinical shoulder tests twice on the same day, by pairs of independent physical therapists. The outcome parameters were observed and specific interrater agreement for positive and negative scores, and interrater reliability (Cohen’s kappa (κ)). Positive and negative interrater agreement values of ≥0.75 were regarded as sufficient for clinical use. For Cohen’s κ, the following classification was used

Lumbosacral transitional vertebrae (LSTV) anomalies may present as bio-mechanical dysfunctions leading to low back pain (LBP). Unilateral or incomplete/partial LSTVs have been documented to be associated with significant sacroiliac joint (SIJ) joint asymmetries. Objective evaluation of outcomes from routine clinical testing for sacral dysfunctions on these subsets of LSTV cannot be found in the literature. Based on quantitative studies available on LSTV-associated anatomical variations at the SIJ, this study hypothesizes probable outcomes of standard palpatory clinical tests used to evaluate sacral dysfunctions in unilateral LSTV anomalies. Since LSTV is reported in a sizeable percentage in the general population and due to its proposed etiological relationship with LBP, these entities warrant attention in terms of the anatomical bases of related clinical assessments and their outcomes, as proposed in this hypothesis.

The growing need for biological information at the single cell level has driven the development of improved cytometry technologies. Flow cytometry is a particularly powerful method that has evolved over the past few decades. Flow cytometers have become essential instruments in biomedical research and routine clinical tests for disease diagnosis, prognosis, and treatment monitoring. However, the increasing number of cellular parameters unveiled by genomic, proteomic, and metabolomic data platforms demands an augmented multiplexability. Also, the need for identification and quantification of relevant biomarkers at low levels requires outstanding analytical sensitivity and reliability. In addition, growing awareness of the advantages associated with miniaturization of analytical devices is pushing forward the progress in integrated and compact, microfluidic-based devices at the point-of-care. In this context, novel types of flow cytometers are emerging during the search to tackle these challenges. Notwithstanding the relevance of other promising alternatives to standard optical flow cytometry (e.g., mass cytometry, various optical and electrical microcytometers), this report focuses on a recent microcytometric technology based on magnetic sensors and magnetic particles integrated into microfluidic structures for dynamic bioanalysis of fluid samples-magnetic flow cytometry. Its concept, main developments, targeted applications, as well as the challenges and trends behind this technology are presented and discussed. Graphical abstract ᅟ "Kindly advise whether there is online abstract figure for this paper. If so, kindly resupply.The graphical abstract is correctly supplied.

The protein cluster comprising a bovine hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), Hb–HSAm cluster (m = 3.0 ± 0.2), is a promising artificial O2 carrier as a red blood cell substitute. Evaluating the safety and efficacy of the Hb–HSAm cluster solution in preclinical and clinical tests necessitates enlargement of the preparation scale and establishment of a simple purification system. This paper describes details of the ideal synthesis of the Hb–HSAm cluster and its O2 binding property. Results show that (i) N-succinimidyl 3-maleimidopropionate (SMP) is an appropriate cross-linker and (ii) anion-exchange chromatography (AEC) is effective for purification. Soluble SMP allows the combination of Hb with HSA in a high protein concentration. Results demonstrate that AEC enables us to separate the cluster and HSA by increasing the ionic strength of the medium. Individual cluster components (Hb–HSA4, Hb–HSA3, Hb–HSA2, and Hb–HSA) showed equal O2 affinity. Furthermore, we conducted chromoge...

Background: Different physical examination tests have been used to preoperatively determine both the presence and size of a primary subscapularis tear. On the contrary, no clinical trial has yet been published to assess the diagnostic validity of the aforementioned tests in diagnosing subscapularis retears after arthroscopic subscapularis repair. Objective: To investigate the diagnostic value of the most commonly used clinical tests in the diagnosis of subscapularis tendon retears after arthroscopic repair. Methods: A retrospective (prospectively collected data) case series involving 37 patients who were suffering from symptomatic complete subscapularis tendon tear was conducted. All patients underwent an all-arthroscopic subscapularis repair with the same operative technique. They were postoperatively evaluated (final end point of follow-up: 12 months) with the use of ultrasound, Constant-Murlay score (CS), bear hug test, internal rotation lag sign, Napoleon test and lift-off test. Sensitivity, specificity, accuracy, positive and negative prognostic values were calculated for each test. Results: Shoulder function was significantly improved according to the final CS. The internal rotation lag sign was the most sensitive for the diagnosis of postoperative subscapularis retears, while the Napoleon sign had the highest specificity. Although postoperative clinical tests yielded no false negative findings, they were poorly predictive as for new ruptures. Ten patients (27%), who were found with a positive (for re-rupture), postoperative, clinical test, had a sonographically intact subscapularis tendon repair. Conclusion: We strongly support the use of subscapularis-specific clinical tests as a composite, in combination with a specific interpretation of their results. If all tests are found negative for retear, then we could assume that the arthroscopic repair remains intact and no further diagnostic examination might be necessary. On the contrary, if at least one subscapularis-specific clinical test is positive for retear, then the patient will likely require additional imaging control for definite diagnosis.