Effect of Fe-O ReaxFF on Liquid Iron Oxide Properties Derived from Reactive Molecular Dynamics.

As iron powder nowadays attracts research attention as a carbon-free, circular energy carrier, molecular dynamics (MD) simulations can be used to better understand the mechanisms of liquid iron oxidation at elevated temperatures. However, prudence must be practiced in the selection of a reactive force field. This work investigates the influence of currently available reactive force fields (ReaxFFs) on a number of properties of the liquid iron-oxygen (Fe-O) system derived (or resulting) from MD simulations. Liquid Fe-O systems are considered over a range of oxidation degrees ZO, which represents the molar ratio of O/(O + Fe), with 0 < ZO < 0.6 and at a constant temperature of 2000 K, which is representative of the combustion temperature of micrometric iron particles burning in air. The investigated properties include the minimum energy path, system structure, (im)miscibility, transport properties, and the mass and thermal accommodation coefficients. The properties are compared to experimental values and thermodynamic calculation results if available. Results show that there are significant differences in the properties obtained with MD using the various ReaxFF parameter sets. Based on the available experimental data and equilibrium calculation results, an improved ReaxFF is required to better capture the properties of a liquid Fe-O system.

Atomistic insight into the effects of electrostatic fields on hydrocarbon reaction kinetics.

Reactive Molecular Dynamics (MD) and Density Functional Theory (DFT) computations are performed to provide insight into the effects of external electrostatic fields on hydrocarbon reaction kinetics. By comparing the results from MD and DFT, the suitability of the MD method in modeling electrodynamics is first assessed. Results show that the electric field-induced polarization predicted by the MD charge equilibration method is in good agreement with various DFT charge partitioning schemes. Then, the effects of oriented external electric fields on the transition pathways of non-redox reactions are investigated. Results on the minimum energy path suggest that electric fields can cause catalysis or inhibition of oxidation reactions, whereas pyrolysis reactions are not affected due to the weaker electronegativity of the hydrogen and carbon atoms. MD simulations of isolated reactions show that the reaction kinetics is also affected by applied external Lorentz forces and interatomic Coulomb forces since they can increase or decrease the energy of collision depending on the molecular conformation. In addition, electric fields can affect the kinetics of polar species and force them to align in the direction of field lines. These effects are attributed to energy transfer via intermolecular collisions and stabilization under the external Lorentz force. The kinetics of apolar species is not significantly affected mainly due to the weak induced dipole moment even under strong electric fields. The dynamics and reaction rates of species are studied by means of large-scale combustion simulations of n-dodecane and oxygen mixtures. Results show that under strong electric fields, the fuel, oxidizer, and most product molecules experience translational and rotational acceleration mainly due to close charge transfer along with a reduction in their vibrational energy due to stabilization. This study will serve as a basis to improve the current methods used in MD and to develop novel methodologies for the modeling of macroscale reacting flows under external electrostatic fields.

Predicting mortality and re-hospitalization for heart failure: a machine-learning and cluster analysis on frailty and comorbidity.

BACKGROUND: Machine-learning techniques have been recently utilized to predict the probability of unfavorable outcomes among elderly patients suffering from heart failure (HF); yet none has integrated an assessment for frailty and comorbidity. This research seeks to determine which machine-learning-based phenogroups that incorporate frailty and comorbidity are most strongly correlated with death or readmission at hospital for HF within six months following discharge from hospital. METHODS: In this single-center, prospective study of a tertiary care center, we included all patients aged 65 and older discharged for acute decompensated heart failure. Random forest analysis and a Cox multivariable regression were performed to determine the predictors of the composite endpoint. By k-means and hierarchical clustering, those predictors were utilized to phenomapping the cohort in four different clusters. RESULTS: A total of 571 patients were included in the study. Cluster analysis identified four different clusters according to frailty, burden of comorbidities and BNP. As compared with Cluster 4, we found an increased 6-month risk of poor outcomes patients in Cluster 1 (very frail and comorbid; HR 3.53 [95% CI 2.30-5.39]), Cluster 2 (pre-frail with low levels of BNP; HR 2.59 [95% CI 1.66-4.07], and in Cluster 3 (pre-frail and comorbid with high levels of BNP; HR 3.75 [95% CI 2.25-6.27])). CONCLUSIONS: In older patients discharged for ADHF, the cluster analysis identified four distinct phenotypes according to frailty degree, comorbidity, and BNP levels. Further studies are warranted to validate these phenogroups and to guide an appropriate selection of personalized, model of care.

Osteoimmunology of Spondyloarthritis.

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.

Bone Involvement in Patients with Spondyloarthropathies.

Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.

A novel effervescent formulation of oral weekly alendronate (70 mg) improves persistence compared to alendronate tablets in post-menopausal women with osteoporosis.

BACKGROUND: A novel effervescent buffered solution of 70 mg alendronate (ALN-EX) was developed to improve upper gastrointestinal (GI) tolerability over alendronate tablets (ALN-T). Whether a better GI tolerability can improve persistence remains to be determined. AIM: This study evaluated persistence and reasons for discontinuation in patients treated with ALN-EX compared to a historical cohort on ALN-T. METHODS: Post-menopausal women (PMW) from a standardized clinical database with BMD T-score < -2.5, or between -2 and -2.5 and at least one vertebral fracture, starting ALN-EX between July 2015 and June 2016 were included. A historical cohort comprised of randomly selected and age-matched PMW on ALN-T was used as a control. Persistence at 6 and 12 months and reasons for discontinuation (e.g. adverse events; AE) were compared between the two groups. RESULTS: A total of 144 PMW on ALN-EX and 216 PMW on ALN-T were analysed. Persistence at 6 and 12 months was 91% and 81% in the ALN-EX group vs. 75% and 69% in the ALN-T group, this difference attaining statistical significance at both 6- (p < 0.001) and 12 months (p = 0.009). A significantly higher proportion of patients receiving ALN-T discontinued treatment due to GI AEs (4% ALN-EX vs. 11% ALN-T; p = 0.027), or patient's decision to discontinue (6% ALN-EX vs. 13% ALN-T; p = 0.016). The adjusted odds ratio of persisting on ALN-EX treatment at 12 months was 2.02 (95% CI: 1.21-3.41, p = 0.008). CONCLUSION: Our findings demonstrate that ALN-EX can provide greater persistence and improved tolerability compared to ALN-T, allowing it to be a viable alternative option in the management of osteoporosis.

Dietary calcium intake in a cohort of individuals evaluated for low bone mineral density: a multicenter Italian study.

BACKGROUND: A low calcium intake is a well-known factor that influences the bone mineral density (BMD) maintenance. In the presence of inadequate calcium intake, secondary hyperparathyroidism develops, leading to an increased bone turnover and fracture risk. AIMS: To assess the dietary calcium intake in relation with osteoporosis and fragility fracture in a cohort of Italian individuals evaluated for low BMD. METHODS: A 7-day food-frequency questionnaire was administered to 1793 individuals, who were consecutively referred at the Centers of the Italian Society for Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) for low BMD. RESULTS: In 30.3% and 20.9% of subjects, the calcium intake was inadequate (< 700 mg/day) and adequate (> 1200 mg/day), respectively. As compared with patients with adequate calcium intake, those with inadequate calcium intake were younger (65.5 ± 10.8 vs 63.9 ± 11.5 years, p = 0.03) and they more frequently reported adverse reactions to food (3.2% vs 7.2% p = 0.01) and previous major fragility fractures (20.8% vs 27.0%, p = 0.03). Patients with calcium intake < 700 mg/day showed a higher prevalence of diabetes mellitus, idiopathic hypercalciuria and food allergy/intolerance (8.1%, 5.1%, 7.2%, respectively) than patients with calcium intake > 700 mg/day (5.3%, 3.0%, 4.1%, respectively, p < 0.04 for all comparisons), also after adjusting for age, gender and body mass index. In 30.3% of fractured subjects, the calcium intake was < 700 mg/day. DISCUSSION: In Italy, a low calcium intake is highly prevalent in individuals at risk for low BMD. Importantly, an inadequate calcium intake is highly prevalent even in patients with history of fragility fractures. CONCLUSIONS: Only about a fifth of patients being assessed for low BMD in an Italian SIOMMMS referral Centre have an adequate calcium intake.

Reactive Molecular Dynamics Investigation of Toluene Oxidation under Electrostatic Fields: Effect of the Modeling of Local Charge Distribution.

A reactive Molecular Dynamics (MD) study of toluene oxidation at high temperatures under externally applied electrostatic fields has been performed. The impact of the modeling of local charge distribution has been investigated by comparing the widely used Charge Equilibration (QEq) method with the Charge Transfer with Polarization Current Equalization (QTPIE) method, which shields charge transfers up to atomic orbitals and introduces molecular polarization. Using the latter method, it is possible to improve the computation of the atomic charges, which are a critical aspect for the numerical study of electric fields, and to capture important effects of the electric field on rotational and vibrational energies of the toluene molecule. Results show that a more comprehensive treatment of inter- and intramolecular charge distribution achieved through the QTPIE method leads to substantially different applied forces and oxidation rates of toluene compared to the QEq method. Using the QTPIE method, no significant effects of the electrostatic field on the toluene oxidation rate were observed for the range of temperatures and pressures studied here, which is in disagreement with the results obtained with the QEq method where a clear impact of the electrostatic field on the average oxidation rate was found. Therefore, when studying electric field effects with MD simulations, the choice of the method used for the charge equilibration is a key modeling assumption whose impact should be carefully evaluated.

The effect of gender on methotrexate prescription attitudes in Italian rheumatoid arthritis patients: the MARI study.

OBJECTIVES: The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy. METHODS: The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender. RESULTS: There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002). CONCLUSIONS: In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

Surgical delay is a risk factor of delirium in hip fracture patients with mild-moderate cognitive impairment.

AIM: To investigate the relationship between onset of delirium and time to surgery in hip fracture (HF) patients with a different degree of cognitive impairment. METHODS: Retrospective analysis of a prospective database of 939 older adults, aged ≥ 75 years admitted with a fragility HF. Subjects underwent a Comprehensive Geriatric Assessment on admission, evaluating health status, prefracture functional status in basic and instrumental activities of daily living, and walking ability. According to the Short Portable Mental Status Questionnaire score, patients were stratified into three categories: cognitively healthy (0-2 errors), mildly to moderately impaired (3-7 errors) and severely impaired (8-10 errors). Time to surgery (from admission) was expressed as days. The occurrence of delirium was ascertained daily by Confusion Assessment Method. RESULTS: Two hundred ninety-two (31.1%) patients experienced delirium during in-hospital stay. They were older, with a higher degree of comorbidity and functional impairment compared to patients without delirium. In multivariate analysis, surgical delay resulted a significant independent risk factor for delirium (HR 1.11, 95% CI 1.01-1.24), along with age, prefracture functional disability and cognitive impairment. When the analysis was performed accounting for the cognitive categories, surgical delay demonstrated to increase the risk of delirium only in the subcategory of mildly to moderately impaired patients, while no significant effect was demonstrated in patients cognitively healthy or severely impaired. CONCLUSIONS: The study supports the concept that older adults with HF should undergo surgery quickly. Patients with mild-to-moderate cognitive impairment should be primarily considered as the best target for interventions aiming to reduce time to surgery.

Atypical femoral fractures in Italy: a retrospective analysis in a large urban emergency department during a 7-year period (2007-2013).

The aim of this study was to determine the incidence of atypical femoral fractures (AFFs) seen in a large emergency department in Italy. It was a retrospective study of all men and women aged 40 years or older admitted to the Emergency Department of Parma University Hospital for a femoral fracture. Cases were identified in the hospital database with use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 820 or 821 or text strings. All the radiographic images of fractures not clearly identified as proximal or condylar were retrieved and evaluated by three independent reviewers. Fractures were considered as atypical if all three reviewers agreed on at least four of five major features defined by the 2013 American Society for Bone and Mineral Research criteria. In the 7-year period (2007-2013), with a total follow-up of 1,383,154 patient-years, we found 22 AFFs in 21 patients, accounting for 7.1% of low-trauma subtrochanteric/femoral shaft fractures and 0.6% of all femoral fractures. The incidence was very low (1.6 in 100,000 patient-years in both sexes combined). In contrast, the incidence of classic fractures of the proximal end of the femur was at least two orders of magnitude higher (typical/atypical rate ratio 152). Bisphosphonate use was reported in 13 patients (62%; mean treatment duration 9 years; range 5-14 years). Among 286 patients with typical subtrochanteric/femoral shaft fractures, 20 were being treated with bisphosphonate (7%; odds ratio 22; 95% confidence interval 8-58; p < 0.001). This study confirms the very low incidence of AFFs in the largest Italian cohort of patients to date. Even though the risk is higher in patients treated with bisphosphonates, AFFs are very rare, and typical femoral fractures are at least 100-fold more frequent.

Pseudoxanthoma Elasticum-Like in ß-Thalassemia Major, a matter of α-Klotho and Parathyroid Hormone?

Pseudoxanthoma elasticum-like (PXL) condition is one of the complications faced by patients with ß-thalassemia major (ß-TM). Histopathological features include abnormal, mineralized and fragmented elastic fibers in skin, eyes and arterial blood vessels (elastorrhexia). The pathogenesis of PXL lesions in ß-TM is not yet completely understood. This study was aimed at analyzing a possible implication of α-Klotho in the clinical manifestation of PXL in patients with ß-TM (30 with and 78 without PXL). A significant correlation was observed between Klotho, parathyroid hormone (PTH) and serum calcium (Ca). Our analysis seems to indicate α-Klotho and PTH as factors that can affect the development of PXL.

Klotho, a new marker for osteoporosis and muscle strength in ß-thalassemia major.

Aim of this study was to compare plasma levels of the secreted protein Klotho in ß-thalassemia major patients and in healthy controls. Also, we examined the existence of correlations between the protein level and osteoporosis, poor muscle strength and fractures. A total of 106 patients with ß-thalassemia major and 95 healthy blood donors were enrolled. Klotho level in plasma was measured by mean of an ELISA test and the hand-grip strength using a dynamometer. Intact parathyroid hormone (PTH), 25-hydroxy vitamin D (Vitamin D), serum calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), ferritin, creatinine were measured by standard clinical techniques. DXA was used to measure bone mineral density (BMD) at the lumbar spine (L2-L4), femoral neck and total hip. We found that the Klotho protein concentration was lower in the blood of patients with ß-thalassemia major than in healthy controls, and it was directly correlated to the hand-grip strength. In ß-thalassemia major patients, the secreted Klotho was lower than in healthy controls. The preliminary investigation into the correlation between markers of osteo- and sarcopenia and Klotho demonstrated a decreased Klotho concentration in ß-TM patients and a higher probability of having had fragility fractures.

Bisphosphonates in the management of thalassemia-associated osteoporosis: a systematic review of randomised controlled trials.

Bisphosphonates are potent inhibitors of bone resorption, widely used for the management of osteoporosis and fracture prevention. Recent evidence suggests that bisphosphonates may have beneficial effects in the treatment of thalassemia-associated osteoporosis, a complex and multifactorial condition. Here we summarise available data about the efficacy and tolerability of bisphosphonates in beta--thalassemic patients. Randomised controlled trials (RCTs) of bisphosphonates in beta-thalassemia were identified searching PubMed. Studies were reviewed to retrieve relevant clinical information. The following variables were considered to assess the safety and efficacy of bisphosphonates-bone mineral density (BMD), markers of bone turnover, incidence of fragility fracture, bone pain, back pain, and clinical adverse events. Five RCTs were identified, investigating alendronate, clodronate, zoledronic acid and neridronate. All bisphosphonates produced a significant decrease of the markers of bone turnover. Alendronate, neridronate, and zoledronic acid significantly improved BMD at the lumbar spine, femoral neck and total hip. Zoledronic acid and neridronate were also shown to reduce bone and back pain. Probably due to the small sample sizes and to the short duration of the trials, it was not possible to establish the anti-fracture efficacy of bisphosphonates; however, they were well tolerated and adverse events were rare but expected on the basis of previous studies. Sufficient evidence exists to support the use of bisphosphonates in the management of thalassemia-associated osteoporosis (to prevent bone loss and improve the BMD). Further research is warranted to establish their anti-fracture efficacy and long-term safety.

Effect of Electric Fields on the Decomposition of Phosphate Esters.

Phosphate esters decompose on metal surfaces and form protective polyphosphate films. For many applications, such as in lubricants for electric vehicles and wind turbines, an understanding of the effect of electric fields on molecular decomposition is urgently required. Experimental investigations have yielded contradictory results, with some suggesting that electric fields improve tribological performance, while others have reported the opposite effect. Here, we use nonequilibrium molecular dynamics (NEMD) simulations to study the decomposition of tri-n-butyl phosphate (TNBP) molecules nanoconfined between ferrous surfaces (iron and iron oxide) under electrostatic fields. The reactive force field (ReaxFF) method is used to model the effects of chemical bonding and molecular dissociation. We show that the charge transfer with the polarization current equalization (QTPIE) method gives more realistic behavior compared to the standard charge equilibration (QEq) method under applied electrostatic fields. The rate of TNBP decomposition via carbon-oxygen bond dissociation is faster in the nanoconfined systems than that in the bulk due to the catalytic action of the surfaces. In all cases, the application of an electric field accelerates TNBP decomposition. When electric fields are applied to the confined systems, the phosphate anions are pulled toward the surface with high electric potential, while the alkyl cations are pulled to the surface with lower potential, leading to asymmetric film growth. Analysis of the temperature- and electric field strength-dependent dissociation rate constants using the Arrhenius equation suggests that, on reactive iron surfaces, the increased reactivity under an applied electric field is driven mostly by an increase in the pre-exponential factor, which is linked to the number of molecule-surface collisions. Conversely, the accelerated decomposition of TNBP on iron oxide surfaces can be attributed to a reduction in the activation energy with increasing electric field strength. Single-molecule nudged-elastic band (NEB) calculations also show a linear reduction in the energy barrier for carbon-oxygen bond breaking with electric field strength, due to stabilization of the charged transition state. The simulation results are consistent with experimental observations of enhanced and asymmetric tribofilm growth under electrostatic fields.

Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component. Unfortunately, the rarity of the disease caused a lack of information about its pathogenesis and molecular landscape. The latest guidelines recommend a multimodal approach that usually includes radical surgery, platinum/etoposide-based chemotherapy, or chemoradiation. Here, we are presenting a case of metastatic mixed adenocarcinoma-large cell neuroendocrine carcinoma of the cervix in a 49-year-old female patient. The molecular characterization of the lesion highlighted the ubiquitous presence of human papillomavirus-18 DNA both in the adenocarcinomatous and the neuroendocrine components, suggesting a role for the virus in the pathogenesis. Moreover, a different set of mutations was detected in the two parts, thus ruling out a possible clonal evolution of the neuroendocrine component from the adenocarcinoma one. More studies are needed to clarify the molecular landscape of these rare lesions and identify putative targets for therapy.

The essential role of combined calcium and vitamin D supplementation in the osteoporosis scenario in italy: Expert opinion paper.

An Italian multidisciplinary working group discussed the current Italian scenario of osteoporosis management during a meeting and highlighted the essential role of calcium and vitamin D supplementation in the prevention of fragility fractures. PURPOSE: This paper aims to review and discuss data on calcium and vitamin D requirements and the role of combined calcium and vitamin D supplementation in the treatment of patients with osteoporosis. METHODS: The discussion of the experts covered literature data on calcium and vitamin D supplementation, gaps in the diagnosis and treatment of osteoporosis, and the role of the primary care physician in identifying and treating patients with osteoporosis. Articles for consideration were identified through PubMed searches using different combinations of pertinent keywords. RESULTS: The discussion highlighted that insufficient calcium or vitamin D intake increases the risk of fragility fractures. The experts also drew attention to the essential role of calcium and vitamin D supplementation in achieving an anti-fracture effect and supporting the efficacy of anti-osteoporotic agents without increasing nephrolithiasis and cardiovascular risks. In addition, the discussion underlined the role of the primary care physician in the initial clinical approach to patients with osteoporosis. CONCLUSIONS: The experts believe that efficient treatment for patients with osteoporosis should include calcium and vitamin D supplementation to achieve adequate levels that are able to inhibit the parathyroid hormone and bone resorption.

Effectiveness of resistance training of masticatory muscles for patients with temporomandibular disorders: protocol for a systematic review.

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.