Multibody Computer Model of the Entire Equine Forelimb Simulates Forces Causing Catastrophic Fractures of the Carpus during a Traditional Race

Simple Summary Palios are traditional horseraces held in the main square of few Italian cities. Due to peculiar features of such circuits, adapted to the square architecture and thus characterized by tight curves and unconventional footing surface, horses involved are at particular risk of accidents. Prevention of catastrophic musculoskeletal injuries is a significant issue and matter of debate during these events. In particular, the negotiation of the curves in the city circuits is a significative concern. An experiment was set up to build a model of entire forelimb at the point of failure in the context of a turn comparable to that in a Palio circuit. The model was informed by live data and the output compared to post-mortem findings obtained from a horse that sustained a catastrophic fracture of the carpus during this competition. The objective of this study is to determine the magnitude and distribution of internal forces generated across the carpus under which the catastrophic injury has occurred and describe related post-mortem findings. A catastrophic fracture of the radial carpal bone experienced by a racehorse during a Palio race was analyzed. Computational modelling of the carpal joint at the point of failure informed by live data was generated using a multibody code for dynamics simulation. The circuit design in a turn, the speed of the animal and the surface characteristics were considered in the model. A macroscopic examination of the cartilage, micro-CT and histology were performed on the radio-carpal joint of the limb that sustained the fracture. The model predicted the points of contact forces generated at the level of the radio-carpal joint where the fracture occurred. Articular surfaces of the distal radius, together with the proximal articular surface of small carpal bones, exhibited diffuse wear lines, erosions of the articular cartilage and subchondral bone exposure. Even though the data in this study originated from a single fracture and further work will be required to validate this approach, this study highlights the potential correlation between elevated impact forces generated at the level of contact surfaces of the carpal joint during a turn and cartilage breakdown in the absence of pre-existing pathology. Computer modelling resulted in a useful tool to inversely calculate internal forces generated during specific conditions that cannot be reproduced in-vivo because of ethical concerns

Serum Resistin and Kidney Function: A Family-Based Study in Non-Diabetic, Untreated Individuals

Background: High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites. Methods: A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise. Results: After adjustments, resistin levels were slightly positively associated with ACR ($\beta \pm$SE = 0.049$\pm$0.023, p = 0.035) and inversely related to eGFR ($\beta \pm$SE = −1.43$\pm$0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (ρg = −0.31$\pm$0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels. Conclusion: Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function

Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes

Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. Results: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10–1.64) and 1.99 (1.55–2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10–1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06–1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). Conclusions: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry

I.S.Mu.L.T. Achilles Tendon Ruptures Guidelines

This work provides easily accessible guidelines for the diagnosis, treatment and rehabilitation of Achilles tendon ruptures. These guidelines could be considered as recommendations for good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care for the individual patient and rationalize the use of resources. This work is divided into two sessions: 1) questions about hot topics; 2) answers to the questions following Evidence Based Medicine principles. Despite the frequency of the pathology andthe high level of satisfaction achieved in treatment of Achilles tendon ruptures, a global consensus is lacking. In fact, there is not a uniform treatment and rehabilitation protocol used for Achilles tendon ruptures

SIRT1 and thrombosis

Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis

The Gray Needle: Large Grains in the HD 15115 Debris Disk from LBT/PISCES/Ks and LBTI/LMIRcam/L' Adaptive Optics Imaging

We present diffraction-limited \ks band and \lprime adaptive optics images of the edge-on debris disk around the nearby F2 star HD 15115, obtained with a single 8.4 m primary mirror at the Large Binocular Telescope. At \ks band the disk is detected at signal-to-noise per resolution element (SNRE) \about 3-8 from \about 1-2\fasec 5 (45-113 AU) on the western side, and from \about 1.2-2\fasec 1 (63-90 AU) on the east. At \lprime the disk is detected at SNRE \about 2.5 from \about 1-1\fasec 45 (45-90 AU) on both sides, implying more symmetric disk structure at 3.8 \microns . At both wavelengths the disk has a bow-like shape and is offset from the star to the north by a few AU. A surface brightness asymmetry exists between the two sides of the disk at \ks band, but not at \lprime . The surface brightness at \ks band declines inside 1\asec (\about 45 AU), which may be indicative of a gap in the disk near 1\asec. The \ks - \lprime disk color, after removal of the stellar color, is mostly grey for both sides of the disk. This suggests that scattered light is coming from large dust grains, with 3-10 \microns -sized grains on the east side and 1-10 \microns dust grains on the west. This may suggest that the west side is composed of smaller dust grains than the east side, which would support the interpretation that the disk is being dynamically affected by interactions with the local interstellar medium.Comment: Apj-accepted March 27 2012; minor correction

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions