Mechanics of Psoas Tendon Snapping. A Virtual Population Study.

Internal snapping of the psoas tendon is a frequently reported condition, especially in young adolescents involved in sports. It is defined as an increased tendon excursion over bony or soft tissue prominence causing local irritation and inflammation of the tendon leading to groin pain and often is accompanied by an audible snap. Due to the lack of detailed dynamic visualization means, the exact mechanism of the condition remains poorly understood and different theories have been postulated related to the etiology and its location about the hip. In the present study we simulated psoas tendon behavior in a virtual population of 40,000 anatomies and compared tendon movement during combined abduction, flexion and external rotation and back to neutral extension and adduction. At risk phenotyopes for tendon snapping were defined as the morphologies presenting with excess tendon movement. There were little differences in tendon movement between the male and female models. In both populations, abnormal tendon excursion correlated with changes in mainly the femoral anatomy (male r = 0.72, p < 0.001, female r = 0.66, p < 0.001): increased anteversion and valgus as well as a decreasing femoral offset and ischiofemoral distance. The observed combination of shape components correlating with excess tendon movement in essence presented with a medial positioning of the minor trochanter. This finding suggest that psoas snapping and ischiofemoral impingement are possibly two presentations of a similar underlying rotational dysplasia of the femur

The Development and Content Validation of the Sjögren's Related Quality of Life Instrument (SRQoL)

INTRODUCTION: Several clinical outcome assessment (COA) instruments assess Sjögren's disease (Sjögren's) symptoms, but do not provide comprehensive assessment of the health-related quality of life (HRQoL) impact of Sjögren's. This study aimed to develop a patient-reported outcome (PRO) instrument for the assessment of HRQoL, intended for use in clinical trials and clinical practice in the assessment of treatment benefit.METHODS: Review of study sponsor proprietary data and qualitative interviews informed the development of a conceptual model, the Sjögren's Related Quality of Life (SRQoL) and patient global impression of severity (PGI-S) and change (PGI-C) items. Combined concept elicitation and cognitive debriefing interviews with patients with Sjögren's explored their HRQoL impact experience and content validity of the SRQoL and PGI items.RESULTS: Twenty participants were interviewed about their Sjögren's experience. Following inductive analysis of interviews, concepts were categorized into eight domains: emotional well-being (e.g., worry and stress; n = 20/20; 100%), sleep (e.g., daytime sleepiness and waking up during the night; n = 20/20; 100%), activities of daily living (e.g., difficulty looking at screens and difficulty driving; n = 20/20; 100%), cognition (e.g., concentration difficulties and word finding difficulties; n = 19/20; 95.0%), physical functioning (e.g., difficulty walking and difficulty exercising; n = 19/20; 95.0%), social and family functioning (e.g., dependent on others and relationship difficulties; n = 17/20; 85.0%), work (n = 15/20; 75.0%), and sexual functioning (n = 12/20; 60.0%). SRQoL and PGI items, instructions, response options, and recall period were well understood and relevant to participants.CONCLUSIONS: The SRQoL is a new PRO instrument to assess Sjögren's impact on HRQoL, developed in accordance with regulatory guidance. This study provides considerable insight into the patient experience of Sjögren's and evidence to support the content validity of the SRQoL. Future research should evaluate the psychometric properties of the SRQoL to support its use in clinical trials and clinical practice and further validate its use as an assessment of treatment benefit.</p

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies

Biocontrol Potential of Forest Tree Endophytes

Peer reviewe

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

This is the final version. Available from Nature Research via the DOI in this record. Data availability: All data used in this review is available from publicly available and herein referenced sources. A list of included studies is provided in Supplementary Data 1. All data generated or analyzed during this study are included in this published article and its supplementary information files. Source data for the figures are available as Supplementary Data 2.BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.Wellcome TrustWellcome Trus

Predicting creditworthiness in retail banking with limited scoring data

The preoccupation with modelling credit scoring systems including their relevance to predicting and decision making in the financial sector has been with developed countries, whilst developing countries have been largely neglected. The focus of our investigation is on the Cameroonian banking sector with implications for fellow members of the Banque des Etats de L'Afrique Centrale (BEAC) family which apply the same system. We apply logistic regression (LR), Classification and Regression Tree (CART) and Cascade Correlation Neural Network (CCNN) in building our knowledge-based scoring models. To compare various models’ performances, we use ROC curves and Gini coefficients as evaluation criteria and the Kolmogorov-Smirnov curve as a robustness test. The results demonstrate that an improvement in terms of predicting power from 15.69% default cases under the current system, to 7.68% based on the best scoring model, namely CCNN can be achieved. The predictive capabilities of all models are rated as at least very good using the Gini coefficient; and rated excellent using the ROC curve for CCNN. Our robustness test confirmed these results. It should be emphasised that in terms of prediction rate, CCNN is superior to the other techniques investigated in this paper. Also, a sensitivity analysis of the variables identifies previous occupation, borrower's account functioning, guarantees, other loans and monthly expenses as key variables in the forecasting and decision making processes which are at the heart of overall credit policy