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Introduction Temporomandibular disorders (TMDs) are musculoskeletal disorders characterised by jaw pain and typically temporomandibular joint limitations. Resistance training (RT) has been shown to be effective at reducing pain and improving function for different musculoskeletal conditions (eg, neck pain, low back pain); however, the effectiveness of RT for patients with TMDs remains unclear. This systematic review will evaluate the effectiveness of RT on pain and temporomandibular joint range of motion in people with TMDs.Methods and analysis The report of this protocol aligns with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The search strategy will be conducted from 1 March 2024 to 31 March 2024 via the following electronic databases: MEDLINE (OVID interface), EMBASE (OVID interface), SCOPUS, Web of Science, PubMed and Cochrane Central Register of Controlled Trials. Any randomised controlled trials or non-randomised studies of interventions in adults with TMD that examine RT targeting the masticatory muscles, compared to other interventions not including RT, will be included. Primary outcomes will be jaw pain intensity and maximal mouth opening. Secondary outcomes will include measures of neuromuscular performance and pressure pain thresholds. Two independent reviewers will conduct the screening of articles for inclusion, data extraction, risk-of-bias assessment using the revised Cochrane risk-of-bias tool for included studies and will evaluate the overall quality of evidence following the Grading of Recommendations Assessment, Development and Evaluation framework. A meta-analysis will be performed where applicable. Alternately, a narrative synthesis will be performed by adhering to the synthesis without meta-analysis guidelines. Data will be summarised according to the outcome measures or, when this is not possible, according to other pertinent variables such as TMD type (ie, temporomandibular joint disorders, masticatory muscle disorders and mixed disorders).Ethics and dissemination Ethical approval is not necessary, since this study does not involve the collection of primary data. The results will be disseminated through presentations at scientific conferences and publication in a peer-reviewed journal.PROSPERO registration number CRD42023476269.

Abstract Sustainable production aims at creating products from processes that minimize environmental impact, energy consumption and natural resources. Customers and markets are ever more leaning towards digital, custom, and flexible solutions with lower environmental impact. Hence, Industry 4.0 (I4.0) solutions are increasingly including social and environmental sustainability aspects. We focus on the realization of an infrastructure integrating industrially relevant application modules by combining system reconfigurability and artificial intelligence, towards sustainable production. To meet the final goal of sustainable production, we address four challenges considering flexibility and sustainability in production in a holistic way: (1) developing infrastructural and methodological tools to support companies to explore the potential of I4.0 towards sustainable production; (2) managing the configurability and customization possibilities of products; (3) effectively handling the flexibility provided by a production system with rapid reconfiguration capabilities; (4) integrating hardware and software flexibility by using reconfigurable robotics and machine learning methods. By developing and connecting different application modules, we obtain a physical demonstrator which represents on the one hand an exemplary scenario of reconfigurable and flexible production system; on the other, it enables new research activities and insights with a see, touch & feel approach for industrial and research realities.

Abstract Stealth solutions of scalar-tensor gravity and less-known de Sitter spaces that generalize them are analyzed regarding their possible role as thermal equilibria at non-zero temperature in the new first-order thermodynamics of scalar-tensor gravity. No stable equilibria are found, further validating the special role of general relativity as an equilibrium state in the landscape of gravity theories, seen through the lens of first-order thermodynamics.

Abstract We consider black holes generically sourced by quantum matter described by regular wavefunctions. This allows for integrable effective energy densities and the removal of Cauchy horizons in spherically symmetric configurations. Moreover, we identify the ultrarigid rotation of the Kerr spacetime as causing the existence of an inner horizon in rotating systems, and describe general properties for quantum matter cores at the centre of rotating black holes with integrable singularities and no Cauchy horizon.

Accurate velocity information is often essential to the control of robot manipulators, especially for precise tracking of fast trajectories. However, joint velocities are rarely directly measured and instead estimated to save costs. While many approaches have been proposed for the velocity estimation of robot joints, no comprehensive experimental evaluation exists, making it difficult to choose the appropriate method. This paper compares multiple estimation methods running on a six degrees-of-freedom manipulator. We evaluate: 1) the estimation error using a ground-truth signal, 2) the closed-loop tracking error, 3) convergence behavior, 4) sensor fault tolerance, 5) implementation and tuning effort. To ensure a fair comparison, we optimally tune the estimators using a genetic algorithm. All estimation methods have a similar estimation error and similar closed-loop tracking performance, except for the nonlinear high-gain observer, which is not accurate enough. Sliding-mode observers can provide a precise velocity estimation despite sensor faults.

Abstract We revisit the analogy between a minimally coupled scalar field in general relativity and a perfect fluid, correcting previous identifications of effective temperature and chemical potential. This provides a useful complementary picture for the first-order thermodynamics of scalar-tensor gravity, paving the way for the Einstein frame formulation (which eluded previous attempts) and raises interesting questions to further develop the analogy.

Introduction: Geometric pattern formation is crucial in many tasks involving large-scale multi-agent systems. Examples include mobile agents performing surveillance, swarms of drones or robots, and smart transportation systems. Currently, most control strategies proposed to achieve pattern formation in network systems either show good performance but require expensive sensors and communication devices, or have lesser sensor requirements but behave more poorly.Methods and result: In this paper, we provide a distributed displacement-based control law that allows large groups of agents to achieve triangular and square lattices, with low sensor requirements and without needing communication between the agents. Also, a simple, yet powerful, adaptation law is proposed to automatically tune the control gains in order to reduce the design effort, while improving robustness and flexibility.Results: We show the validity and robustness of our approach via numerical simulations and experiments, comparing it, where possible, with other approaches from the existing literature.

Static and stationary regular black holes are examined under a minimal set of requirements consisting of (i) the existence of a well defined event horizon and (ii) the weak energy condition for matter sourcing the geometry. We perform our analysis by means of the gravitational decoupling approach and find hairy solutions free of curvature singularities. We identify the matter source producing a deformation of the Minkowski vacuum such that the maximum deformation is the Schwarzschild solution for the static case, and the Kerr metric for the stationary case.

Trajectory planning is a crucial and challenging problem for research on intelligent robotic and mechatronic systems, which play a pivotal role in modern manufacturing processes, and especially within the framework of Industry 4 [...]

Abstract Since, in Einstein gravity, a massless scalar field with lightlike gradient behaves as a null dust, one could expect that it can act as the matter source of Vaidya geometries. We show that this is impossible because the Klein–Gordon equation forces the null geodesic congruence tangent to the scalar field gradient to have zero expansion, contradicting a basic property of Vaidya solutions. By contrast, exact plane waves travelling at light speed and sourced by a scalar field acting as a null dust are possible.

Abstract It is now established that, contrary to common belief, (electro-)vacuum Brans–Dicke gravity does not reduce to general relativity (GR) for large values of the Brans–Dicke coupling $$\omega $$ ω . Since the essence of experimental tests of scalar–tensor gravity consists of providing lower bounds on $$\omega $$ ω , in light of the misguided assumption of the equivalence between the limit $$\omega \rightarrow \infty $$ ω→∞ and the GR limit of Brans–Dicke gravity, the parametrized post-Newtonian (PPN) formalism on which these tests are based could be in jeopardy. We show that, in the linearized approximation used by the PPN formalism, the anomaly in the limit to general relativity disappears. However, it survives to second (and higher) order and in strong gravity. In other words, while the weak gravity regime cannot tell apart GR and $$\omega \rightarrow \infty $$ ω→∞ Brans–Dicke gravity, when higher order terms in the PPN analysis of Brans–Dicke gravity are included, the latter never reduces to the one of GR in this limit. This fact is relevant for experiments aiming to test second order light deflection and Shapiro time delay.

We consider the quantum description of a toy model universe in which the Schwarzschild-de Sitter geometry emerges from the coherent state of a massless scalar field. Although highly idealised, this simple model allows us to find clear hints supporting the conclusion that the reaction of the de Sitter background to the presence of matter sources induces i) a modified Newtonian dynamics at galactic scales and ii) different values measured for the present Hubble parameter. Both effects stem from the conditions required to have a normalisable quantum state.

Lung cancer remains the leading cause of cancer deaths worldwide. International societies have promoted the molecular analysis of MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping for the clinical stratification of non-small cell lung cancer (NSCLC) patients. Different technical approaches are available to detect MET exon 14 skipping in routine practice. Here, the technical performance and reproducibility of testing strategies for MET exon 14 skipping carried out in various centers were evaluated. In this retrospective study, each institution received a set (n = 10) of a customized artificial formalin-fixed paraffin-embedded (FFPE) cell line (Custom METex14 skipping FFPE block) that harbored the MET exon 14 skipping mutation (Seracare Life Sciences, Milford, MA, USA), which was previously validated by the Predictive Molecular Pathology Laboratory at the University of Naples Federico II. Each participating institution managed the reference slides according to their internal routine workflow. MET exon 14 skipping was successfully detected by all participating institutions. Molecular analysis highlighted a median Cq cut off of 29.3 (ranging from 27.1 to 30.7) and 2514 (ranging from 160 to 7526) read counts for real-time polymerase chain reaction (RT-PCR) and NGS-based analyses, respectively. Artificial reference slides were a valid tool to harmonize technical workflows in the evaluation of MET exon 14 skipping molecular alterations in routine practice.

Enforcing the cessation of motion is a common action in robotic systems to avoid the damage that the robot can exert on itself, its environment or, in shared environments, people. This procedure raises two main concerns, which are addressed in this paper. On the one hand, the stopping procedure should respect the collision free path computed by the motion planner. On the other hand, a sudden stop may produce large current peaks and challenge the limits of the motor’s control capabilities, as well as degrading the mechanical performance of the system, i.e., increased wear. To address these concerns, we propose a novel method to enforce a mechanically feasible, smooth and path-consistent stop of the robot based on a time-minimization algorithm. We present a numerical implementation of the method, as well as a numerical study of its complexity and convergence. Finally, an experimental comparison with an off-the-shelf stopping scheme is presented, showing the effectiveness of the proposed method.

Loss of bone and muscle mass and strength (i. e., osteosarcopenia) is a highly prevalent clinical condition in older adults, associated with an increased risk of fragility fractures and unfavorable clinical outcomes. Although sarcopenia is a potential risk factor for osteoporosis and subsequent fracture, and the management of this hazardous duet is the key to preventing osteoporotic fracture, evidence pertaining to the treatment of sarcopenia for the purpose of preventing fragile fractures remains insufficient. Given this scenario we aimed at prospectively compare the long-term effectiveness of bisphosphonates vs. denosumab, on bone and muscle, in a cohort of old age hip fractured patients by virtue of a timely osteo-metabolic and sarcopenic assessment. Ninety-eight patients consecutively enrolled at the IRCCS Hospital San martino, Genoa, Italy, received at baseline comprehensive geriatric assessment and Bone Densitometry (DXA) with the quantitative and quantitative bone analysis and evaluation of relative skeletal muscle index (RSMI) and longitudinally after 1 year form hip surgery. The results showed a slightly and non-significant osteo-metabolic improvement in the Alendronate group compared to the Denosumab group, and a positive trend of RSMI measurements in the Denosumab group. Although preliminary in nature, this is the first report to longitudinally analyze osteosarcopenia in a real-world cohort of very old age patients after hip fracture and moved a step forward in the understanding of the best osteo-metabolic therapy for long- term treatment, exploring as well the potential dual role of denousumab as antiresorptive and muscle strength specific drug for osteosarcopenia in this vulnerable population.

Abstract We study the extent of quantum gravitational effects in the internal region of non-singular, Hayward-like solutions of Einstein’s field equations according to the formalism known as horizon quantum mechanics. We grant a microscopic description to the horizon by considering a huge number of soft, off-shell gravitons, which superimpose in the same quantum state, as suggested by Dvali and Gomez. In addition to that, the constituents of such a configuration are understood as loosely confined in a binding harmonic potential. A simple analysis shows that the resolution of a central singularity through quantum physics does not tarnish the classical description, which is bestowed upon this extended self-gravitating system by General Relativity. Finally, we estimate the appearance of an internal horizon as being negligible, because of the suppression of the related probability caused by the large number of virtual gravitons.

The construction sector is one of the major global economies and is characterised by low productivity and high inefficiencies, but could highly benefit from the introduction of robotic equipment in terms of productivity, safety, and quality. As the development and the availability of robotic solutions for the construction sector increases, the evaluation of their potential benefits compared to conventional processes that are currently adopted on construction sites becomes compelling. To this end, we exploit Bayesian decision theory and apply an axiomatic design guideline for the development of a decision-theoretic expert system that: (i) evaluates the utility of available alternatives based on evidence; (ii) accounts for uncertainty; and (iii) exploits both expert knowledge and preferences of the users. The development process is illustrated by means of exemplary use case scenarios that compare manual and robotic processes. A use case scenario that compares manual and robotic marking and spraying is chosen for describing the development process in detail. Findings show how decision making in equipment selection can be supported by means of dedicated systems for decision support, developed in collaboration with domain experts.

Abstract The horizon quantum mechanics is an approach that was previously introduced in order to analyze the gravitational radius of spherically symmetric systems and compute the probability that a given quantum state is a black hole. In this work, we first extend the formalism to general space-times with asymptotic (ADM) mass and angular momentum. We then apply the extended horizon quantum mechanics to a harmonic model of rotating corpuscular black holes. We find that simple configurations of this model naturally suppress the appearance of the inner horizon and seem to disfavor extremal (macroscopic) geometries.

We try to shed some light on the role of matter in the final stages of black hole evaporation from the fundamental frameworks of classicalization and the black-to-white hole bouncing scenario. Despite being based on very different grounds, these two approaches attempt at going beyond the background field method and treat black holes as fully quantum systems rather than considering quantum field theory on the corresponding classical manifolds. They also lead to the common prediction that the semiclassical description of black hole evaporation should break down and the system be disrupted by internal quantum pressure, but they both arrive at this conclusion neglecting the matter that formed the black hole. We instead estimate this pressure from the bootstrapped description of black holes, which allows us to express the total Arnowitt–Deser–Misner mass in terms of the baryonic mass still present inside the black hole. We conclude that, although these two scenarios provide qualitatively similar predictions for the final stages, the corpuscular model does not seem to suggest any sizeable deviation from the semiclassical time scale at which the disruption should occur, unlike the black-to-white hole bouncing scenario. This, in turn, makes the phenomenology of corpuscular black holes more subtle from an astrophysical perspective.

We develop several formal analogies between the logistic equation and the spatially homogeneous and isotropic relativistic cosmology described by the Einstein–Friedmann equations. These analogies produce an effective Lagrangian and Hamiltonian and new symmetries for the logistic equation.

Bootstrapped Newtonian gravity was developed with the purpose of estimating the impact of quantum physics in the nonlinear regime of the gravitational interaction, akin to corpuscular models of black holes and inflation. In this work, we set the ground for extending the bootstrapped Newtonian picture to cosmological spaces. We further discuss how such models of quantum cosmology can lead to a natural solution to the cosmological constant problem.

We consider the effects of gravitons in the collapse of baryonic matter that forms a black hole. We first note that the effective number of (soft off-shell) gravitons that account for the (negative) Newtonian potential energy generated by the baryons is conserved and always in agreement with Bekenstein's area law of black holes. Moreover, their (positive) interaction energy reproduces the expected post-Newtonian correction and becomes of the order of the total ADM mass of the system when the size of the collapsing object approaches its gravitational radius. This result supports a scenario in which the gravitational collapse of regular baryonic matter produces a corpuscular black hole without central singularity, in which both gravitons and baryons are marginally bound and form a Bose–Einstein condensate at the critical point. The Hawking emission of baryons and gravitons is then described by the quantum depletion of the condensate and we show the two energy fluxes are comparable, albeit negligibly small on astrophysical scales. Keywords: Gravitational collapse, Black holes, No singularity

The application of robotics in construction is hindered by the site environment, which is unstructured and subject to change. At the same time, however, buildings and corresponding sites can be accurately described by Building Information Modeling (BIM). Such a model contains geometric and semantic data about the construction and operation phases of the building and it is already available at the design phase. We propose a method to leverage BIM for simple yet efficient deployment of robotic systems for construction and operation of buildings. With our proposed approach, BIM is used to provide the robot with a priori geometric and semantic information on the environment and to store information on the operation progress. We present two applications that verify the effectiveness of our proposed method. This system represents a step forward towards an easier application of robots in construction.

Decision making is a relevant task in the building construction sector, and various systems and methods for decision support are emerging. By means of a systematic literature review, this article identifies the methods for decision making in building construction and the lifecycle phases for which decision support systems are proposed. The selected articles are analyzed and grouped according to the adopted decision-making methods and the defined lifecycle phases. The findings show that multiple criteria decision analysis is the most used method for decision support in building construction and that the construction phase is the most addressed phase within the relevant existing works. The findings related to the construction phase are further refined by grouping the articles into application areas and by reviewing in detail the proposed methods therein. The scarce availability of data and project cases is identified as the most common barrier for the successful development and implementation of decision support systems in the building construction sector. This work provides a basis for scientists and practitioners for identifying suitable methods for decision-making support in a specific lifecycle phase of a building.

We study a quantum-corrected Schwarzschild black hole proposed recently in Loop Quantum Gravity. Prompted by the fact that corrections to the innermost stable circular orbit of Schwarzschild diverge, we investigate time-like and null radial geodesics. Massive particles moving radially outwards are confined, while photons make it to infinity with infinite redshift. This unsettling physics, which deviates radically from both Schwarzschild (near the horizon) and Minkowski (at infinity) is due to repulsion by the negative quantum energy density that makes the quasilocal mass vanish as one approaches spatial infinity.

The many technical and computational problems that appear to be constantly emerging in various branches of physics and engineering beg for a more detailed understanding of the fundamental mathematics that serves as the cornerstone of our way of understanding natural phenomena [...]

In this paper, after a brief review of the physical notion of quality factor in viscoelasticity, we present a complete discussion of the attenuation processes emerging in the Maxwell–Prabhakar model, recently developed by Giusti and Colombaro. Then, taking profit of some illuminating plots, we discuss some potential connections between the presented model and the modern mathematical modelling of seismic processes.

Hip fracture (HF) is a common event in older adults and is associated with significant morbidity, mortality, reduction of quality of life and costs for the healthcare systems. The expected rise in the total number of HF worldwide, due to improvements in life expectancy, and the growing awareness of HF detrimental consequences have led to the development and implementation of models of care alternative to the traditional ones for the acute and post-acute management of HF older adults. These services were set to streamline hospital care, minimize inhospital complications, provide early discharge, improve short- and long-term functional and clinical outcomes, and reduce healthcare costs associated with hip and other fragility fractures. The main feature that distinguishes these models is the different healthcare professional that retains the responsibility and leadership during the acute and post-acute phases. This narrative review has been conceived to provide a brief description of the models implemented in the last twenty years, to describe their potential beneficial effects on the shortand long-term outcomes, and to define the strengths and limitations of these models. On the basis of available studies, it seems that the more complex and sophisticated services, characterized by a multidisciplinary approach with a co-leadership (geriatrician and orthopedic surgeon) or a geriatrician leadership demonstrated to produce better outcomes compared to the traditional or simplest models.

Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional and prospective studies. Due to the high epidemiological and clinical impact of this newly discovered comorbidity of acromegaly, this topic has progressively become more important and prominent over the years, and the pertinent literature has been enriched by new findings on the pathophysiology and treatment. The aim of this narrative review was to discuss these novel findings, integrating them with the seminal observations, in order to give the reader an updated view of how the field of acromegaly and bone is developing, from strong clinical observations to a mechanistic understanding and possible prevention and treatment.

Summary: Obesity is characterized by the accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys), without a concomitant increase in apoptosis. These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRβ repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest a potential role for partially dysfunctional PD-1+CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.

Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and Methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition.

Abstract Background We applied an artificial intelligence-based model to predict fragility fractures in postmenopausal women, using different dual-energy x-ray absorptiometry (DXA) parameters. Methods One hundred seventy-four postmenopausal women without vertebral fractures (VFs) at baseline (mean age 66.3 ± 9.8) were retrospectively evaluated. Data has been collected from September 2010 to August 2018. All subjects performed a spine x-ray to assess VFs, together with lumbar and femoral DXA for bone mineral density (BMD) and the bone strain index (BSI) evaluation. Follow-up exams were performed after 3.34 ± 1.91 years. Considering the occurrence of new VFs at follow-up, two groups were created: fractured versus not-fractured. We applied an artificial neural network (ANN) analysis with a predictive tool (TWIST system) to select relevant input data from a list of 13 variables including BMD and BSI. A semantic connectivity map was built to analyse the connections among variables within the groups. For group comparisons, an independent-samples t-test was used; variables were expressed as mean ± standard deviation. Results For each patient, we evaluated a total of n = 6 exams. At follow-up, n = 69 (39.6%) women developed a VF. ANNs reached a predictive accuracy of 79.56% within the training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map showed that a low BSI at the total femur is connected to the absence of VFs. Conclusion We found a high performance of ANN analysis in predicting the occurrence of VFs. Femoral BSI appears as a useful DXA index to identify patients at lower risk for lumbar VFs.

An unbiased and replicable profiling of type 1 diabetes (T1D)-specific circulating immunome at disease onset has yet to be identified due to experimental and patient selection limitations. Multicolor flow cytometry was performed on whole blood from a pediatric cohort of 107 patients with new-onset T1D, 85 relatives of T1D patients with 0-1 islet autoantibodies (pre-T1D_LR), 58 patients with celiac disease or autoimmune thyroiditis (CD_THY) and 76 healthy controls (HC). Unsupervised clustering of flow cytometry data, validated by a semi-automated gating strategy, confirmed previous findings showing selective increase of naïve CD4 T cells and plasmacytoid DCs, and revealed a decrease in CD56brightNK cells in T1D. Furthermore, a non-selective decrease of CD3+CD56+ regulatory T cells was observed in T1D. The frequency of naïve CD4 T cells at disease onset was associated with partial remission, while it was found unaltered in the pre-symptomatic stages of the disease. Thanks to a broad cohort of pediatric individuals and the implementation of unbiased approaches for the analysis of flow cytometry data, here we determined the circulating immune fingerprint of newly diagnosed pediatric T1D and provide a reference dataset to be exploited for validation or discovery purposes to unravel the pathogenesis of T1D.

Backgroundacute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients.Methodscross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality.Resultstwo hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 – 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004).Discussionwe described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.

With the aim of finding a suitable synthesizable superalkali species, using the B3LYP/6-31G* density functional level of theory we provide results for the interaction between the buckminsterfullerene C60 and the superalkali Li3F2. We show that this endofullerene is stable and provides a closed environment in which the superalkali can exist and interact with CO2. It is worthwhile to mention that the optimized Li3F2 structure inside C60 is not the most stable C2v isomer found for the “free” superalkali but the D3h geometry. The binding energy at 0 K between C60 and Li3F2 (D3h) is computed to be 119 kJ mol−1. Once CO2 is introduced in the endofullerene, it is activated, and the OCO^ angle is bent to 132°. This activation does not follow the previously studied CO2 reduction by an electron transfer process from the superalkali, but it is rather an actual reaction where a F (from Li3F2) atom is bonded to the CO2. From a thermodynamic analysis, both CO2 and the encapsulated [Li3F2⋅CO2] are destabilized in C60 with solvation energies at 0 K of 147 and < −965 kJ mol−1, respectively.

ABSTRACT Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Abstract  All hip fracture (HF) subjects are candidates for calcium and vitamin D (CaD) supplementation. Up to 50% of HF older adults present with secondary hyperparathyroidism (HPTH) resulting from hypovitaminosis D on hospital admission. To investigate the patterns and predictors of persistence with CaD supplementation in the elderly after HF, we considered all patients aged 70 years or older who were discharged alive after surgical repair of HF in the period of 1 year from an Orthopaedic Unit. Baseline characteristics of the subjects and osteoporosis treatment prescribed at discharge were retrieved from medical record review. A telephone interview at 6 months evaluated whether patients were currently taking CaD supplementation. Nonpersistence was defined when subjects ceased therapy within 6 months. Univariate and multivariate models were applied to determine the relationship between 6 months persistence with CaD and the variables collected: age, living situation, prescription of a bisphosphonate, baseline walking ability, number of drugs used, presence of dementia, number of active clinical issues at discharge (ACIs), discharge location, and being referred to a center for metabolic bone diseases (preplanned visit) at discharge. Of 428 subjects enrolled, 117 were excluded for different reasons (incomplete data, no therapy, death). A total of 311 subjects were discharged with a prescription of CaD (calcium 1,000 mg, cholecalciferol 800 UI, once daily) and were considered for the analysis. At 6 months, only 114 patients (36.7%) were currently taking CaD supplementation. In a univariate analysis, the following variables were significantly related with persistence: absence of dementia, prescription of a bisphosphonate, six or fewer drugs being used (drugs used ≤6), two or less ACIs (≤2 ACIs) at discharge, ability to walk without aid at baseline, being discharged home, and being referred to a preplanned visit. In a multivariate model, the prescription of a bisphosphonate at discharge (OR 3.178, 95% CI 1.477–6.836, P = 0.003), a preplanned visit (OR 1.953, 95% CI 1.066–3.514, P = 0.03), the absence of dementia (OR 1.877, 95% CI 1.021–3.451, P = 0.043), and ≤6 drugs used (OR 1.842, 95% CI 1.066–3.182, P = 0.029) remained the most significant predictors of persistence with CaD. In HF elderly, who are at high risk of hypovitaminosis D and HPTH, persistence with CaD supplementation is very low. The enrolment in a postsurgical program for the management of bone disease can significantly increase persistence. Moreover, factors related to the complexity of older adult patients (polypharmacotherapy, dementia) seem to be particularly important in compliance with prescribed drugs. [ABSTRACT FROM AUTHOR]

Tatiana Mancini1, Teresa Porcelli2, Andrea Giustina21Department of Internal Medicine and Medical Specialties, San Marino Hospital, San Marino, Republic of San Marino, 2Department of Medical and Surgical Sciences, University of Brescia, Brescia, ItalyAbstract: Endogenous Cushing syndrome is an endocrine disease caused by excessive secretion of adrenocorticotropin hormone in approximately 80% of cases, usually by a pituitary corticotroph adenoma (Cushing disease [CD]). It is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. The goals of treatment of CD include the reversal of clinical features, the normalization of biochemical changes with minimal morbidity, and long-term control without recurrence. Generally, the treatment of choice is the surgical removal of the pituitary tumor by transsphenoidal approach, performed by an experienced surgeon. Considering the high recurrence rate, other treatments should be considered. Second-line treatments include more radical surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. Drug treatment has been targeted at the hypothalamic or pituitary level, at the adrenal gland, and also at the glucocorticoid receptor level. Frequently, medical therapy is performed before surgery to reduce the complications of the procedure, reducing the effects of severe hypercortisolism. Commonly, in patients in whom surgery has failed, medical management is often essential to reduce or normalize the hypercortisolemia, and should be attempted before bilateral adrenalectomy is considered. Medical therapy can be also useful in patients with CD while waiting for pituitary radiotherapy to take effect, which can take up to 10 years or more. So far, results of medical treatment of CD have not been particularly relevant; however, newer tools promise to change this scenario. The aim of this review is to analyze the results and experiences with old and new medical treatments of CD and to reevaluate medical therapies for complications of CD and hypopituitarism in patients with cured CD.Keywords: ketoconazole, somatostatin analogs, dopamine agonists, rosiglitazone, Cushing disease, glucocorticoids, hypopituitarism

BACKGROUND: The long-acting somatostatin analogue octreotide is used either as an adjuvant or primary therapy to lower growth hormone (GH) levels in patients with acromegaly and may also induce pituitary tumor shrinkage. OBJECTIVE: We performed a meta-analysis to accurately assess the effect of octreotide on pituitary tumor shrinkage. DATA SOURCES: A computerized Medline and Embase search was undertaken to identify potentially eligible studies. STUDY ELIGIBILITY CRITERIA: Eligibility criteria included treatment with octreotide, availability of numerical metrics on tumor shrinkage and clear definition of a clinically relevant reduction in tumor size. Primary endpoints included the proportion of patients with tumor shrinkage and mean percentage reduction in tumor volume. DATA EXTRACTION AND ANALYSIS: The electronic search identified 2202 articles. Of these, 41 studies fulfilling the eligibility criteria were selected for data extraction and analysis. In total, 1685 patients were included, ranging from 6 to 189 patients per trial. For the analysis of the effect of octreotide on pituitary tumor shrinkage a random effect model was used to account for differences in both effect size and sampling error. RESULTS: Octreotide was shown to induce tumor shrinkage in 53.0% [95% CI: 45.0%-61.0%] of treated patients. In patients treated with the LAR formulation of octreotide, this increased to 66.0%, [95% CI: 57.0%-74.0%). In the nine studies in which tumor shrinkage was quantified, the overall weighted mean percentage reduction in tumor size was 37.4% [95% CI: 22.4%-52.4%], rising to 50.6% [95% CI: 42.7%-58.4%] with octreotide LAR. LIMITATIONS: Most trials examined were open-label and had no control group. CONCLUSIONS: Octreotide LAR induces clinically relevant tumor shrinkage in more than half of patients with acromegaly.

Background. The role of bisphosphonates (BPs) in the management of patients with hypercalciuria (HC) associated with osteoporosis is still uncertain. The aim of the study was to evaluate the effect of alendronate and indapamide alone or in combination on bone mineral density (BMD) and 24-h urinary calcium excretion (24-CaU) in post-menopausal women with HC and low BMD. Methods. A total of 77 post-menopausal women with HC (24-CaU > 4mg/kg/day) and low BMD [T-score Results. Overall 67 women completed the study and were included in the final analysis. Patients in the three groups were similar with regard to baseline characteristics. BMD did not significantly change from baseline after 1 year of treatment with indapamide (LS: +1 ± 3.1%; FN: −0.3 ± 3.5%; TH: −0.4 ± 3.1%), while it showed a significant increase from baseline in the other two groups (ALN; LS: +5.8 ± 4.2%, P P = 0.018; TH: +2 ± 3.6%, P = 0.006) (ALN + IND; LS: +8.2 ± 5.3%, P P = 0.007; TH: +2.9 ± 4.2%, P = 0.004). Patients in the combination group showed a significantly higher increase of BMD at LS compared to ALN (P = 0.04). After 1 year, 24-CaU values significantly decreased from baseline in all groups (IND, 239 ± 78 versus 364 ± 44, P P P P P = 0.012). Conclusions. These results show a benefit, in terms of BMD improvement and 24-CaU reduction, associated with BPs’ therapy in combination with indapamide in HC associated with osteoporosis. The combination therapy demonstrated a reduction of 24-CaU and an increase in LS BMD superior to that observed with alendronate alone. Our results support a new potential approach with BPs associated with thiazide diuretics or indapamide in the management of post-menopausal women with HC and associated bone loss. Studies on the larger sample size are needed to demonstrate the efficacy on the fracture outcome. [ABSTRACT FROM AUTHOR]