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Musculoskeletal ultrasound has become a practical and accessible diagnostic tool for musculoskeletal diseases. It is used to examine joints, tendons, vessels, and nerves due to its wide availability in rheumatology practice. Ultrasound has also been applied for years in other areas such as muscular injuries in sports activities and rheumatic diseases with inflammation such as myositis. The knowledge among rheumatologists about muscle ultrasound is increasingly growing taking into account it is not the main target of their ultrasound activity but mainly based on the evaluation of joint, synovitis, tenosynovitis, vasculitis in giant cell arteritis, and parotid gland evaluation in Sjögren´s syndrome. Thus, the present review describes anatomical and ultrasound findings including all muscles of the thigh (anterior, posterior, medial aspects) and leg (anterior, lateral, posterior superficial, deep posterior compartments) of lower limb structures to ease a comprehensive clinical and sonographic evaluation.

Abstract Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches.

Abstract Background Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. Methods We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient’s standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). Results ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. Conclusions ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.

Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN-38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two-compartment model with first-order elimination, with SN-38 formed directly by a first-order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN-38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN-38 clearance. Model evaluation was satisfactory for both irinotecan and SN-38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN-38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN-38 concentrations. In summary, the PKs of total irinotecan and SN-38 after administration of liposomal irinotecan were well-described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.

Abstract Introduction Exercise therapy is usually prescribed as first-line treatment for lower limb tendinopathies. The multitude of exercise- and non-exercise-based management options can be overwhelming for the treating sports professional and patient alike. We chose to investigate the comparative effectiveness of exercise therapy with or without adjuncts for managing the commonest lower limb tendinopathies. Methods Through an extensive systematic literature search using multiple databases, we aimed to identify eligible randomised controlled trials (RCTs) on Achilles tendinopathy, patellar tendinopathy or greater trochanteric pain syndrome (GTPS) that included at least one exercise intervention in their treatment arms. Our primary outcomes were patient-reported pain and function (Victorian Institute of Sport Assessment; VISA). Follow-up was defined as short-term (≤ 12 weeks), mid-term (> 12 weeks to

Background: Low muscle mass quantity/quality is needed to confirm sarcopenia diagnosis; however, no validated cut-off points exist. This study aimed to determine the diagnostic accuracy of sarcopenia through muscle mass quantity/quality parameters, using the bioimpedance analysis (BIA), isokinetic, and ultrasound tools in probable sarcopenic community-dwelling older adults (≥60 years). Also, it aimed to suggest possible new cut-off points to confirm sarcopenia diagnosis. Methods: A cross-sectional exploratory analysis study was performed with probable sarcopenic and non-sarcopenic older adults. BIA, isokinetic, and ultrasound parameters were evaluated. The protocol was registered on ClinicalTrials.gov (NCT05485402). Results: A total of 50 individuals were included, 38 with probable sarcopenia (69.63 ± 4.14 years; 7 men and 31 women) and 12 non-sarcopenic (67.58 ± 4.54 years; 7 men and 5 women). The phase angle (cut-off: 5.10° men, p = 0.003; 4.95° women, p < 0.001), peak torque (cut-off: 66.75 Newtons-meters (N-m) men, p < 0.001; 48.35 N-m women, p < 0.001), total work (cut-off: 64.00 Joules (J) men, p = 0.007; 54.70 J women, p = 0.001), and mean power (cut-off: 87.8 Watts (W) men, p = 0.003; 48.95 W women, p = 0.008) in leg extension, as well as the the forearm muscle thickness (cut-off: 1.41 cm (cm) men, p = 0.017; 0.94 cm women, p = 0.041), had great diagnostic accuracy in both sexes. Conclusions: The phase angle, peak torque, total work, and mean power in leg extension, as well as forearm muscle thickness, had great diagnostic accuracy in regard to sarcopenia, and the suggested cut-off points could lead to the confirmation of sarcopenia diagnosis, but more studies are needed to confirm this.

Key points Certain radiological findings of acute muscle injury on MRI performed shortly prior to return to play may be considered risk factors of reinjury. There is a high risk of reinjury when two of these five radiological findings are present (connective tissue gap, loss of tendon tension, intermuscular oedema, callus gap and interstitial feather oedema). Despite appropriate progression during rehabilitation, MRI studies appear necessary in the decision to return to competition.

Musculoskeletal ultrasound has become a practical and accessible diagnostic tool for musculoskeletal diseases. It is used to examine joints, tendons, vessels, and nerves due to its wide availability in rheumatology practice. Ultrasound has also been applied for years in other areas such as muscular injuries in sports activities and rheumatic diseases with inflammation such as myositis. The knowledge among rheumatologists about muscle ultrasound is increasingly growing taking into account it is not the main target of their ultrasound activity but mainly based on the evaluation of joint, synovitis, tenosynovitis, vasculitis in giant cell arteritis, and parotid gland evaluation in Sjögren's syndrome. Thus, the present review describes anatomical and ultrasound findings including all muscles of the thigh (anterior, posterior, medial aspects) and leg (anterior, lateral, posterior superficial, deep posterior compartments) of lower limb structures to ease a comprehensive clinical and sonographic evaluation. [ABSTRACT FROM AUTHOR]

Muscle injuries and subsequent reinjuries significantly impact athletes, especially in football. These injuries lead to time loss, performance impairment, and long-term health concerns. This review aims to provide a comprehensive overview of the current understanding of muscle reinjuries, delving into their epidemiology, risk factors, clinical management, and prevention strategies. Despite advancements in rehabilitation programs and return-to-play criteria, reinjury rates remain alarmingly high. Age and previous muscle injuries are nonmodifiable risk factors contributing to a high reinjury rate. Clinical management, which involves accurate diagnosis, individualized rehabilitation plans, and the establishment of return-to-training and return-to-play criteria, plays a pivotal role during the sports season. Eccentric exercises, optimal loading, and training load monitoring are key elements in preventing reinjuries. The potential of artificial intelligence (AI) in predicting and preventing reinjuries offers a promising avenue, emphasizing the need for a multidisciplinary approach to managing these injuries. While current strategies offer some mitigation, there is a pressing need for innovative solutions, possibly leveraging AI, to reduce the incidence of muscle reinjuries in football players. Future research should focus on this direction, aiming to enhance athletes’ well-being and performance.

The consumption of out-of-home meals is increasing. This study is aimed at assessing the effect of an intervention on healthy offerings and the management of food allergies and intolerances. Ten (control group) and eight restaurants (intervention group) were randomized in a 12-month parallel controlled trial. The outcomes were changes regarding adherence to the Mediterranean diet (AMed) and gluten management (SMAP) criteria, the traffic light rating category, nutrients, and gluten- and allergen-free content of dishes. After 12 months, and compared with baseline, there was an improvement of ≥25% in four items of the AMed criteria in the intervention group, whereas an increase in the offer of dairy desserts without added sugar, and a decrease in the first course offerings of vegetables and/or legumes were observed in the control group (p < 0.05). Also, after 12 months, there was an improvement of ≥50% in four SMAP criteria (p < 0.05) and in the mean average of all SMAP criteria (p = 0.021) compared with baseline in the intervention group, in which intra- and inter-group improvements for desserts in traffic light ratings, nutrients, and allergens were observed (p < 0.05). Therefore, the intervention showed beneficial effects, improving the quality of menus toward the Mediterranean diet pattern and gluten and food allergy/intolerance management.

Abstract The physiological effects of physical exercise are ubiquitously reported as beneficial to the cardiovascular and musculoskeletal systems. Exercise is widely promoted by medical professionals to aid both physical and emotional wellbeing; however, mechanisms through which this is achieved are less well understood. Despite numerous beneficial attributes, certain types of exercise can inflict significant significant physiological stress. Several studies document a key relationship between exercise and immune activation. Activation of the innate immune system occurs in response to exercise and it is proposed this is largely mediated by cytokine signalling. Cytokines are typically classified according to their inflammatory properties and evidence has shown that cytokines expressed in response to exercise are diverse and may act to propagate, modulate or mitigate inflammation in musculoskeletal health. The review summarizes the existing literature on the relationship between exercise and the immune system with emphasis on how exercise-induced cytokine expression modulates inflammation and the immune response.

Abstract Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN‐38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI‐1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two‐compartment model with first‐order elimination, with SN‐38 formed directly by a first‐order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN‐38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN‐38 clearance. Model evaluation was satisfactory for both irinotecan and SN‐38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN‐38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN‐38 concentrations. In summary, the PKs of total irinotecan and SN‐38 after administration of liposomal irinotecan were well‐described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.

The PID controller is the most common option in the realm of control applications and is dominant in the process control industry. Among the related analytical methods, Internal Model Control (IMC) has gained remarkable industrial acceptance due to its robust nature and good set-point responses. However, the traditional application of IMC results in poor load disturbance rejection for lag-dominant and integrating plants. This work presents an IMC-like design method which avoids this common pitfall and is devised to work well for plants of modest complexity, for which analytical PID tuning is plausible. For simplicity, the design only focuses on the closed-loop sensitivity function. The approach provides model-based tuning of single-loop PID controllers in terms of the robustness/performance and servo/regulator trade-offs. Although the robustness/performance compromise is commonly considered, it is not so common to also take into account, for example, the conflict between input and output disturbances, referred also as the servo/regulator trade-off. As interested in providing a unified tuning approach, it is shown how the proposed methodology allows to deal with different process dynamics in a unified way.

Abstract The purpose of the present study was to compare the relative absorption of a new powder presentation of silicon (Si) as orthosilicic acid with maltodextrin (Orgono Powder) compared to usual Si liquid presentations as orthosilicic acid with Equisetum arvense and Rosmarinus officinalis (G5 Siliplant) and orthosilicic acid with aloe vera (G7 Aloe). All dietary supplements were administered at the same Si oral dose (21.6 mg) in a randomized, double-blind, crossover post-prandial study conducted in 5 healthy men. Urine was collected at baseline and over the 6-h post-dose period in 2 separate 3-h collections for the analysis of Si concentration, which was conducted by inductively coupled plasma optical emission spectrometry as the gold standard method. No significant differences in total urinary Si excretion were found after the intake of these 3 dietary supplements; 34.6%, 32.4% and 27.2% of the ingested Si from G7 Aloe, G5 Siliplant and Orgono Powder, respectively, was excreted in urine over the 6-h follow-up period. The 3 different oral Si formulations tested, in powder and liquid presentations, provide highly bioavailable Si and present an equivalent relative absorption in healthy humans.