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Context: Currently, Chagas disease represents an important public health problem affecting more than 8 million people worldwide. The vector of this disease is the Trypanosoma cruzi (Tc) parasite. Our research specifically focuses on the structure and aggregation states of the enzyme aldo-keto reductase of Tc (TcAKR) reported in this parasite. TcAKR belongs to the aldo-keto reductase (AKR) superfamily, enzymes that catalyze redox reactions involved in crucial biological processes. While most AKRs are found in monomeric forms, some have been reported to form dimeric and tetrameric structures. This is the case for some TcAKR. To better understand how TcAKR multimers form and remain stable, we conducted a comprehensive computational analysis using molecular dynamics (MD) simulations. Our approach to elucidating the aggregation states of TcAKR involved two strategies. Initially, we explored the dynamic behaviour of pre-assembled TcAKR dimers. Subsequently, we examined the self-aggregation of eight monomers. This investigation led to the identification of crucial residues that contribute to the stabilization of protein-protein interactions. It was also found that TcAKRs can form stable supramolecular assemblies, with each monomer typically surrounded by three first neighbours. These findings align with experimental reports of tetrameric or more complex supramolecular structures. Our computational studies could guide further experimental investigations aiming at drug development and assist in designing strategies to modulate aggregation. Method: Atomistic molecular dynamics simulations were carried out. The TcAKR 3D model structure was obtained by homology modelling using the Swiss Model for the TcAKR sequence (GenBank accession no. EU558869). Further, we checked the model with Alphafold2 and found a high degree of similarity between models. Several tools were used to build the dimers including CLUSPRO, GRAMM-Docking, Hdock, and Py-dock. Protein superstructures were built using the PACKMOL package. CHARMM-GUI was used to set up the simulation systems. GROMACS version 2020.5 was used to perform the simulations with the CHARMM36 force field for the protein and ions and the TIP3P model for water. Further analyses were performed using VMD, GROMACS, AMBER tools, MDLovoFit, bio3d, and in-house programs. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the role of myocardial perfusion imaging (MPI) stress tests using stress cardiac magnetic resonance (sCMR) and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in non-cardiac surgery (NCS) pre-operatory management. Materials and methods: This monocentric retrospective study enrolled patients with coronary artery disease or a minimum of two cardiovascular risk factors undergoing intermediate-to-high-risk non-cardiac surgeries. The primary composite endpoint comprised cardiac death, cardiogenic shock, acute coronary syndromes (ACS), and cardiogenic pulmonary edema occurring within 30 days after surgery, while the secondary endpoint was ACS. Results: A total of 1590 patients were enrolled; among them, 669 underwent a MPI stress test strategy (sCMR: 287, SPECT-MPI: 382). The incidence of 30-day cardiac events was lower in the stress-tested group compared to the non-stress-tested group (1.2% vs. 3.4%; p 0.006). Adopting a stress test strategy showed a significant reduction in the risk of the composite endpoint (OR: 0.33, 95% CI: 0.15–0.76, p 0.009) and ACS (OR: 0.41, 95% CI: 0.17–0.98, p 0.046) at multivariable analysis, with similar cardiac events rate between stress CMR and SPECT (1.1% vs. 1.3%, p 0.756). Stress CMR showed a greater accuracy to predict coronary artery revascularizations (sCMR c-statistic: 0.95, ischemic cut-point: 5.5%; SPECT c-statistic: 0.85, ischemic cut-point: 7.5%). Conclusion: Stress test strategy is related to a lower occurrence of cardiac events in high-risk patients scheduled for intermediate-to-high-risk non-cardiac surgeries. Both sCMR and SPECT-MPI comparably reduce the likelihood of cardiac complications, albeit sCMR offers greater accuracy in predicting coronary artery revascularization. [ABSTRACT FROM AUTHOR]

This paper presents a framework designed to collect, archive, and share time series data coming from sensor networks at Istituto Nazionale di Geofisica e Vulcanologia, Osservatorio Etneo (Italy), which we have developed and called Time Series Database management System (TSDSystem). The framework proposes a flexible database model for the standardization of sensor networks data and implements an optimized technology for storage and retrieval of acquired time series data. It is designed for the implementation of multiparametric databases and then suitable for development in volcanological observatories worldwide. The proposed framework provides a web service to perform writing and reading data via a standard web communication protocol, which easily enables interaction with other instruments or automatic systems. All results provided by the TSDSystem web service are represented using common data formats in the context of online services. In particular, the station networks metadata representation follows a schema inspired by the International Federation of Digital Seismograph Networks, widely known in seismology. A web GUI (graphical user interface) is provided to test and document the web service. Additionally, basic built-in web applications are supplied with the web GUI to perform joint and synchronized time series data visualization as well as representation of stations on a geographical map. The web GUI also offers administration tools for data access policy management, creation of monitoring dashboards and data publication through web pages. The framework implements an authorization system that can be used to restrict both writing or reading operations. The TSDSystem can also be a useful tool for engineering surveillance systems. The implementing code of the framework is available with an open source license on a public repository together with a user manual. [ABSTRACT FROM AUTHOR]

Aims: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. Methods and results: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63–0.98; HF: HR = 1.00, 95% CI 0.82–1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71–0.92; HF: HR = 0.97, 95% CI 0.81–1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72–0.89; HF: HR = 1.00 95% CI 0.88–1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78–0.96; HF: HR = 0.83, 95% CI 0.72–0.95, pinteraction = 0.69). Conclusion: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264). [ABSTRACT FROM AUTHOR]

Abstract The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo‐substitutes support the formation of new blood vessels and neuromuscular junctions—pivotal aspects for cell survival and muscle contractile functionalities—together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo‐substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

Background: Burn injuries occurring due to thermal, electrical, flame-related, and chemical causes result in acute and chronic wounds. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are both autologous platelet concentrates (APCs) that may augment wound healing. We conducted a systematic review to examine patient outcomes when this biologic technology is used in the management of burn wounds. Methods: The following databases were queried to identify relevant articles used for literature review: PubMed, Embase, and Scopus. The main outcome measures of this review were efficacy of PRP and PRF for use in primary burn wounds, skin graft donor site wounds, and skin graft adherence. Results: Our review identified 14 eligible articles, reporting on a total of 781 patients. Included studies investigated PRP (n = 12) and PRF (n = 2) in the context of primary burn wounds and skin grafting. Overall, PRP and PRF were shown to accelerate burn wound re-epithelialization and healing, though there was less consensus with regards to the effects on scar quality. Additionally, PRP and PRF were demonstrated to improve graft take and skin graft donor site healing. No significant adverse events or reactions were reported in the literature. However, prolonged operative time, the necessity for multiple venipunctures, and a lack of significant improvement in healthcare costs present notable limitations of this therapy. Conclusions: PRP and PRF may improve wound healing and may be considered as adjunct therapies in the treatment of primary burn wounds and skin graft donor site wounds. We encourage future, high-quality, prospective studies to be conducted to help fill these knowledge gaps and improve clinicians' understanding of the use of PRP and PRF for burn wound and skin graft donor wound healing. Level of Evidence: Not ratable [ABSTRACT FROM AUTHOR]

Infrasound signals are used to investigate and monitor active volcanoes during eruptive and degassing activity. Infrasound amplitude information has been used to estimate eruptive parameters such as plume height, magma discharge rate, and lava fountain height. Active volcanoes are characterized by pronounced topography and, during eruptive activity, the topography can change rapidly, affecting the observed infrasound amplitudes. While the interaction of infrasonic signals with topography has been widely investigated over the past decade, there has been limited work on the impact of changing topography on the infrasonic amplitudes. In this work, the infrasonic signals accompanying 57 lava fountain paroxysms at Mt. Etna (Italy) during 2021 were analyzed. In particular, the temporal and spatial variations of the infrasound amplitudes were investigated. During 2021, significant changes in the topography around the most active crater (the South East Crater) took place and were reconstructed in detail using high resolution imagery from unoccupied aerial system surveys. Through analysis of the observed infrasound signals and numerical simulations of the acoustic wavefield, we demonstrate that the observed spatial and temporal variation in the infrasound signal amplitudes can largely be explained by the combined effects of changes in the location of the acoustic source and changes in the near-vent topography, together with source acoustic amplitude variations. This work demonstrates the importance of accurate source locations and high-resolution topographic information, particularly in the near-vent region where the topography is most likely to change rapidly and illustrates that changing topography should be considered when interpreting local infrasound observations over long time scales. [ABSTRACT FROM AUTHOR]

Abstract Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro‐generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG‐fibrinogen hydrogel. Once engineered to express placental‐derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG‐fibrinogen‐embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient‐specific muscle creation for a large number of pathological conditions involving muscle tissue wasting.

Purpose of Review: Heart failure (HF) is commonly associated with iron deficiency (ID), defined as insufficient levels of iron to meet physiological demands. ID's association with anaemia is well understood but it is increasingly recognised as an important comorbidity in HF, even in the absence of anaemia. This review summarises contemporary evidence for the measurement and treatment of ID, in both HFrEF and HFpEF, and specific HF aetiologies, and highlights important gaps in the evidence-base. Recent Findings: ID is common among patients with HF and associated with increased morbidity and mortality. Correcting ID in patients with HF can impact upon functional status, exercise tolerance, symptoms, and overall quality of life, irrespective of anaemia status. Summary: ID is a modifiable comorbidity in HF. Therefore, recognising and treating ID has emerging therapeutic potential and is important for all clinicians who care for patients with HF to understand the rationale and approach to treatment. [ABSTRACT FROM AUTHOR]

Five tephra layers named BRH1 to 5 were sampled in an ice cliff located on the north-eastern flank of Mount Melbourne (northern Victoria Land, Antarctica). The texture, componentry, mineralogy, and major and trace element compositions of glass shards have been used to characterize these layers. These properties suggest that they are primary fall deposits produced from discrete eruptions that experienced varying degrees of magma/water interaction. The major and trace element glass shard analyses on single glass shards indicate that Mount Melbourne Volcanic Field is the source of these tephra layers and the geochemical diversity highlights that the eruptions were fed by compositionally diverse melts that are interpreted to be from a complex magma system with a mafic melt remobilizing more evolved trachy-andesitic to trachytic magma pockets. Geochemical compositions, along with textural and mineralogical data, have allowed correlations between two of the englacial tephra and distal cryptotephra from Mount Melbourne, recovered within a marine sediment core in the Edisto Inlet (~ 280 km northeast of Mount Melbourne), and constrain the age of these englacial tephra layers to between the third and the fourth century CE. This work provides new evidence of the intense historical explosive activity of the Mount Melbourne Volcanic Field and better constrains the rates of volcanism in northern Victoria Land. These data grant new clues on the eruptive dynamics and tephra dispersal, and considerably expand the geochemical (major and trace elements) dataset available for the Mount Melbourne Volcanic Field. In the future, this will facilitate the precise identification of tephra layers from this volcanic source and will help define the temporal and spatial correlation between Antarctic records using tephra layers. Finally, this work also yields new valuable time-stratigraphic marker horizons for future dating, synchronization, and correlations of different palaeoenvironmental and palaeoclimatic records across large regions of Antarctica. [ABSTRACT FROM AUTHOR]

Cardiac conduction system pacing provides physiological ventricular activation by directly stimulating the conduction system. This review describes the two types of conduction system pacing: His bundle pacing (HBP) and left bundle area pacing (LBAP). The most significant advantage of HB pacing is that it can provide a regular, narrow QRS; however, the disadvantages are challenging implantation and a high risk of re-intervention due to lead dislodgement and the development of high pacing threshold. LBAP provides optimum physiological activation of the left ventricle by engaging the left bundle/fascicular fibers. LBAP is more physiological than traditional RV apical pacing and could be an attractive alternative to conventional cardiac resynchronization therapy (CRT). The advantages of LBAP are a relatively more straightforward implantation technique than HBP, better lead stability and pacing thresholds. HBP and LBAP are more physiological than right ventricular pacing and may be used instead of conventional pacemakers. Both HBP and LBBP are being investigated as alternatives to conventional CRT. [ABSTRACT FROM AUTHOR]

Microseism is the continuous background seismic signal caused by the interaction between the atmosphere, the hydrosphere and the solid Earth. Several studies have dealt with the relationship between microseisms and the tropical cyclones, but none focused on the small-scale tropical cyclones that occur in the Mediterranean Sea, called Medicanes. In this work, we analysed the Medicane Apollo which impacted the eastern part of Sicily during the period 25 October–5 November 2021 causing heavy rainfall, strong wind gusts and violent sea waves. We investigated the microseism accompanying this extreme Mediterranean weather event, and its relationship with the sea state retrieved from hindcast maps and wave buoys. The spectral and amplitude analyses showed the space–time variation of the microseism amplitude. In addition, we tracked the position of Apollo during the time using two different methods: (i) a grid search method; (ii) an array analysis. We obtained a good match between the real position of Apollo and the location constraint by both methods. This work shows that it is possible to extract information on Medicanes from microseisms for both research and monitoring purposes. [ABSTRACT FROM AUTHOR]

Introduction: The safety of performing one-stage bilateral total hip arthroplasty (THA) remains controversial among the orthopedic community. The aim of the present study was to determine the incidence and predictors of blood transfusions in one-stage bilateral THA performed in a high-volume single center. Patients and methods: Patients undergoing one-stage bilateral THA between 2015 and 2017 were included. The following data were collected from the hospital medical records: age, body mass index (BMI), American Society of Anaesthesiologists (ASA) score, smoking habit, comorbidities, preoperative serum creatinine, serum iron, ferritin, C-reactive protein (CRP), and hemoglobin (Hb). The Hb levels at postoperative day 1 and 3 were also collected. Results: A total of 367 patients with a mean age of 56.1 years (range, 32–79) were included. Forty-eight (13%) patients were transfused with a mean number of 1.6 blood units per patient. In non-transfused patients, the average Hb drop was 3.6 (SD ± 1) g/dL and 4.9 g/dL (SD ± 1.3) at postoperative day 1 and day 3, respectively. The average preoperative Hb level was 14.64 (SD ± 1.21) g/dL. In the univariate logistic regression, the following variables were predictive factors for transfusions: male gender (OR 0.447; P = 0.01), preoperative hemoglobin level (OR 0.622; P = 0.001), preoperative ferritin level (OR 0.995; P = 0.016), BMI (OR 0.837; P = 0.001), cardiopathy (OR 3.534; P = 0.046), preoperative anaemia (OR 10.54; P = 0.011). In the multivariate logistic regression only preoperative hemoglobin level (OR 0.666; P = 0.01), and BMI (OR 0.868; P = 0.007) were statistically significant. Conclusions: The incidence of blood transfusions after one-stage bilateral THA is low in non-anemic patients operated on at a high-volume arthroplasty center. The main predictors of blood transfusions are preoperative Hb level and BMI. [ABSTRACT FROM AUTHOR]

Infrasound is increasing applied as a tool to investigate magma dynamics at active volcanoes, especially at open-vent volcanoes, such as Mt. Etna (Italy), which are prodigious sources of infrasound. Harmonic infrasound signals have been used to constrain crater dimensions and track the movement of magma within the shallow plumbing system. This study interprets the remarkable systematic change in monotonic infrasound signals preceding a lava fountaining episode at Mt. Etna on 20 February 2021. We model the changing tones (0.7 to 3 Hz fundamental frequency) as a rise in the magma column from 172 ± 25 m below the crater rim to 78 ± 8 m over the course of 24 h. The infrasonic gliding disappears approximately 4 h before the onset of lava fountaining as the magma column approaches the flare of the crater and acoustic resonance is no longer supported. The featured 20 February event was just one of 52 lava fountain episodes that occurred at Mt. Etna over the course of 9 months in 2021 and was the only lava fountain episode where dramatic gliding was observed as a subsequent partial collapse of the crater prevented future resonance. The results presented here demonstrate that analysis of infrasonic gliding can be used to track the position of the magma free surface and hence may provide information on the processes taking place within the plumbing system before eruptive activity. [ABSTRACT FROM AUTHOR]

The tiger mosquito, Aedes albopictus, has adjusted well to urban environments by adopting artificial water containers as oviposition sites. Its spread in temperate regions is favoured by the deposition of cold-tolerant diapausing eggs that survive winter temperatures to a certain degree. The probability of establishment in new geographical areas is estimated using predictive models usually based on meteorological data measured at coarse resolution. Here, we investigated if we could obtain more precise and realistic risk scenarios for the spread of Ae. albopictus when considering the winter microclimatic conditions of catch basins, one of the major sites of oviposition and egg overwintering in temperate urban areas. We monitored winter microclimatic conditions of catch basins in four Swiss cities and developed a regression model to predict the average microclimatic temperatures of catch basins, based on available meteorological parameters, accounting for the observed differences between cities. We then used the microclimatic model to correct the predictions of our previously developed risk model for the prediction of Ae. albopictus establishment. Comparison of the predictive model's results based on local climate data and microclimate data indicated that the risk of establishment for Ae. albopictus in temperate urban areas increases when microhabitat temperatures are considered. [ABSTRACT FROM AUTHOR]

Purpose of the Review: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. Recent Findings: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Summary: Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications. [ABSTRACT FROM AUTHOR]

Introduction: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) is not routinely recommended for the diagnosis of infective endocarditis (IE) due to the lack of clinical impact. Materials and methods: Between January 2016 and January 2020, clinical data from patients with a possible diagnosis of IE were reviewed retrospectively to evaluate the value of 18F-FDG-PET/CT in the diagnosis of IE. 18F-FDG PET/CT scan was performed as an additional diagnostic tool in possible IE when echocardiography was inconclusive or in patients with definite IE to identify extracardiac complications. Cases were classified according to modified Duke criteria as rejected, definite or possible. Results: 313 patients with suspected IE were included. 72 (23%) patients underwent 18F-FDG PET/CT. 18F-FDG PET/CT resulted in a reclassification of Duke criteria in 29/72 (40%) patients, from "possible" to "definite" (n, 10) and to "rejected" (n, 19). Patients who benefited from a Duke criteria reclassification following 18F-FDG PET/CT were more frequently classified as possible IE at inclusion or had a non-conclusive baseline echocardiography (100% vs 58%; p 0.001) and had more likely a prosthetic metallic valve replacement (59% vs 21%; p 0.001). Abnormal perivalvular uptake was identified in 46 patients (71% prosthetic vs 50% native; p 0.118). 18F-FDG PET/CT identified extracardiac uptake consistent with septic emboli in 14/72 (19%) patients. In addition, extracardiac uptake indicative of an alternative diagnosis was identified in 5 patients (2% prosthetic vs 17% native; p 0.039). Conclusion: The use of 18F-FDG-PET/CT has shown to be useful in the diagnosis of IE, particularly in prosthetic IE and may provide additional value in the detection of septic emboli and/or the identification of an alternative diagnosis different from IE. [ABSTRACT FROM AUTHOR]

Introduction: Culture-negative infective endocarditis (IE) accounts for 7–31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE. Methods: Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens. Results: 36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei. Conclusion: 16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed. [ABSTRACT FROM AUTHOR]

The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4–5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4–5D. Guidance is provided for clinicians caring for CKD stages 4–5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism. [ABSTRACT FROM AUTHOR]

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture. [ABSTRACT FROM AUTHOR]

The key players of the chronic kidney disease-mineral and bone disorders (CKD-MBD) are calcium, phosphate, PTH, FGF23, and the vitamin D hormonal system. The progressive reduction of kidney function greatly modifies the tightly interrelated mechanisms that control these parameters. As a result, important changes occur in the bone and mineral hormonal axis, leading to changes in bone turnover with relevant consequences in clinical outcomes, such as decrease in bone mass with increased bone fragility and bone fractures and increased vascular and valvular calcification, also with great impact in the cardiovascular outcomes. So far, the knowledge of the mineral and bone disorders in CKD and the increased variety of efficacious therapies should lead to a better prevention and management of CKD-MBD. [ABSTRACT FROM AUTHOR]

In the course of chronic kidney disease (CKD), alterations in the bone-vascular axis augment the risk of bone loss, fractures, vascular and soft tissue calcification, left ventricular hypertrophy, renal and myocardial fibrosis, which markedly increase morbidity and mortality rates. A major challenge to improve skeletal and cardiovascular outcomes in CKD patients requires a better understanding of the increasing complex interactions among the main modulators of the bone-vascular axis. Serum parathyroid hormone (PTH), phosphorus (P), calcium (Ca), fibroblast growth factor 23 (FGF23), calcidiol, calcitriol and Klotho are involved in this axis interact with RANK/RANKL/OPG system and the Wnt/β-catenin pathway. The RANK/RANKL/OPG system controls bone remodeling by inducing osteoblast synthesis of RANKL and downregulating OPG production and it is also implicated in vascular calcification. The complexity of this system has recently increased due the discovery of LGR4, a novel RANKL receptor involved in bone formation, but possibly also in vascular calcification. The Wnt/β-catenin pathway plays a key role in bone formation: when this pathway is activated, bone is formed, but when it is inhibited, bone formation is stopped. In the progression of CKD, a downregulation of the Wnt/β-catenin pathway has been described which occurs mainly through the not coincident elevations of sclerostin, Dickkopf1 (Dkk1) and the secreted Frizzled Related Proteins (sFRPs). This review analyzes the interactions of PTH, P, Ca, FGF23, calcidiol, calcitriol and Klotho with the RANKL/RANKL/OPG system and the Wnt/β-catenin, pathway and their implications in bone and cardiovascular disorders in CKD. [ABSTRACT FROM AUTHOR]

The most common neurologic symptoms in COVID-19 are headache, anosmia, and dysgeusia. Optic neuritis is an unusual manifestation of SARS-CoV-2 infection. We report a case of a patient who initially consulted for vision loss in the absence of respiratory symptoms. She was diagnosed with optic neuritis following SARS-CoV-2 infection. Delay in diagnosis of neuro-ophthalmic manifestations of COVID-19 may lead to irreversible optic atrophy. A mechanism in which viral antigens would induce an immune response against self-proteins, or direct SARS Cov-2 infection of the central nervous system, may be involved in optic nerve injury. [ABSTRACT FROM AUTHOR]

Open conduit basaltic volcanoes can be potentially hazardous as the eruptive activity may turn suddenly from a steady state to highly explosive. Unexpected changes in explosion intensity are recurrent at Stromboli volcano, where major explosions and large-scale paroxysms sometimes break off the ordinary, Strombolian activity with little or no warning. Two powerful paroxysmal eruptions took place at Stromboli volcano during the summer 2019, causing widespread fires, consistent damages across the island, injuries and one fatality. Prediction of similar events is really challenging for the modern volcanology, though models propaedeutic to early-warning monitoring systems are not properly assessed yet in many volcanoes worldwide. Here, we present a multi-parametric study that combines petrological and geophysical data to investigate processes generating the two paroxysms. The time information derived by Li enrichments in plagioclase crystals correlates with tilt time series derived by seismometers installed on the island, highlighting the dominant role of shallow conduit processes in triggering the 2019 paroxysmal activity. Our dataset conceives a mechanism of gas slug formation and fast upward migration that finally triggered the eruptions in very limited times. The proposed model questions our capability to forecast such kind of paroxysms in times that are rapid enough to allow mitigation of the associated risk. [ABSTRACT FROM AUTHOR]

The NF-κB pathway represents a crucial signaling mechanism in sensing and integrating a multitude of environmental and intracellular stimuli and directing a coordinated response that from the cellular level may impact on the entire organism. A plethora of chaperone proteins work at multiple steps of the pathway, from membrane receptor activation to transcription factor binding to DNA. Indeed, chaperones are required to assist protein conformational changes, to assemble supramolecular complexes and to regulate protein ubiquitination, required for pathway activation. Some chaperones acquired a role as integral components of the signaling complexes, needed for signal progression. Here we describe the chaperones involved in the NF-κB pathway and their specific roles in the different contexts. [ABSTRACT FROM AUTHOR]

Although light is essential for photosynthesis, when in excess, it may damage the photosynthetic apparatus, leading to a phenomenon known as photoinhibition. Photoinhibition was thought as a light-induced damage to photosystem II; however, it is now clear that even photosystem I may become very vulnerable to light. One main characteristic of light induced damage to photosystem II (PSII) is the increased turnover of the reaction center protein, D1: when rate of degradation exceeds the rate of synthesis, loss of PSII activity is observed. With respect to photosystem I (PSI), an excess of electrons, instead of an excess of light, may be very dangerous. Plants possess a number of mechanisms able to prevent, or limit, such damages by safe thermal dissipation of light energy (non-photochemical quenching, NPQ), slowing-down of electron transfer through the intersystem transport chain (photosynthesis-control, PSC) in co-operation with the Proton Gradient Regulation (PGR) proteins, PGR5 and PGRL1, collectively called as short-term photoprotection mechanisms, and the redistribution of light between photosystems, called state transitions (responsible of fluorescence quenching at PSII, qT), is superimposed to these short term photoprotective mechanisms. In this manuscript we have generated a number of higher order mutants by crossing genotypes carrying defects in each of the short-term photoprotection mechanisms, with the final aim to obtain a direct comparison of their role and efficiency in photoprotection. We found that mutants carrying a defect in the ΔpH-dependent photosynthesis-control are characterized by photoinhibition of both photosystems, irrespectively of whether PSBS-dependent NPQ or state transitions defects were present or not in the same individual, demonstrating the primary role of PSC in photoprotection. Moreover, mutants with a limited capability to develop a strong PSBS-dependent NPQ, were characterized by a high turnover of the D1 protein and high values of Y(NO), which might reflect energy quenching processes occurring within the PSII reaction center. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) anatomy has routinely been considered an exclusion in the setting of transcatheter aortic valve implantation (TAVI) because of the large dimension of the aortic annulus having a more calcified, bulky, and irregular shape. The study aims to develop a patient-specific computational framework to virtually simulate TAVI in stenotic BAV patients using the Edwards SAPIEN 3 valve (S3) and its improved version SAPIEN 3 Ultra and quantify stent frame deformity as well as the severity of paravalvular leakage (PVL). Specifically, the aortic root anatomy of n.9 BAV patients who underwent TAVI was reconstructed from pre-operative CT imaging. Crimping and deployment of S3 frame were performed and then followed by fluid-solid interaction analysis to simulate valve leaflet dynamics throughout the entire cardiac cycle. Modeling revealed that the S3 stent frame expanded well on BAV anatomy with an elliptical shape at the aortic annulus. Comparison of predicted S3 deformity as assessed by eccentricity and expansion indices demonstrated a good agreement with the measurement obtained from CT imaging. Blood particle flow analysis demonstrated a backward blood jet during diastole, whereas the predicted PVL flows corresponded well with those determined by transesophageal echocardiography. This study represents a further step towards the use of personalized simulations to virtually plan TAVI, aiming at improving not only the efficacy of the implantation but also the exploration of "off-label" applications as the TAVI in the setting of BAV patients. Graphical abstract Computational frameworks of TAVI in patients with stenotic bicuspid aortic valve. [ABSTRACT FROM AUTHOR]

Visfatin/extracellular-nicotinamide-phosphoribosyltranferase-(eNampt) is a multifaceted adipokine enhanced in type-2-diabetes and obesity. Visfatin/eNampt cause in vitro endothelial dysfunction and vascular inflammation, although whether the same effects are achieved in vivo is unknown. Toll-like receptor-4 (TLR4), a main surface pattern recognition receptor of innate immune system is a potential target for visfatin/eNampt. We studied its capacity to generate vascular dysfunction in vivo, focusing on TLR4 role and downstream activation of nod-like-receptor-protein-3 (NLRP3)-inflammasome. 4 month-old C57BL/6 mice were exposed to 7 days infusion of visfatin/eNampt, alone or together with FK 866 (Nampt enzymatic inhibitor), CLI 095 (TLR4 blocker), MCC 950 (NLRP3-inflammasome inhibitor), or anakinra (interleukin(IL)-1-receptor antagonist). Endothelial dysfunction was tested in isolated microvessels. In human umbilical endothelial cells (HUVEC), proteins related to the NLRP3-inflammasome phosphorylated p-65, NLRP3, caspase-1, pro-IL-1β, and mature IL-1β were determined by Western blot, while the inflammasome related apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC-specks) was studied by immunofluorescence. Impaired endothelium-dependent relaxations were observed in isolated mesenteric microvessels from visfatin/eNampt-infused mice. This effect was attenuated by co-treatment with FK 866 or CLI 095, supporting a role for Nampt enzymatic activity and TLR4 activation. Moreover, cultured HUVEC exposed to visfatin/eNampt showed higher expression and activation of NLRP3-inflammasome. Again, this effect relied on Nampt enzymatic activity and TLR4 activation, and it was abrogated by the inflammasome assembly blockade with MCC 950. The endothelial dysfunction evoked by visfatin/eNampt infusion in vivo was also sensitive to both MCC 950 and anakinra treatments, suggesting that the NLRP3-inflammasome-driven tissular release of IL-1β is the final mediator of endothelial damage. We conclude that Visfatin/eNampt produces in vivo vascular dysfunction in mice by a Nampt-dependent TLR4-mediated pathway, involving NLRP3-inflammasome and paracrine IL-1β. Thus, those targets may become therapeutic strategies for attenuating the adipokine-mediated vascular dysfunction associated to obesity and/or type-2-diabetes. [ABSTRACT FROM AUTHOR]

Heart failure is a complex clinical syndrome and represents the final path of numerous heart diseases. Coronary artery disease is recognized as the primary risk factor for heart failure development, being the main etiological factor in more than 50% of heart failure patients in North America and Europe. Regardless of overt coronary artery disease, myocardial ischemia is a common finding in failing hearts, likely due to structural or functional coronary circulation alterations. Ischemia is a self-propagating process which irreversibly impairs the cardiac function and negatively impacts prognosis. Thus, a better and thorough understanding of myocardial ischemia pathophysiology in heart failure would likely lead to significantly improved outcomes in these patients. This review aims to describe the mechanisms of myocardial ischemia and coronary artery disease in heart failure, focusing on coronary circulation dysfunctions due to increased parietal stress or non-obstructive coronary disease, and discussing the association and management of coronary artery disease in patients with heart failure. [ABSTRACT FROM AUTHOR]

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD. [ABSTRACT FROM AUTHOR]

We propose a three-dimensional non-hydrostatic shock-capturing numerical model for the simulation of wave propagation, transformation and breaking, which is based on an original integral formulation of the contravariant Navier-Stokes equations, devoid of Christoffel symbols, in general time-dependent curvilinear coordinates. A coordinate transformation maps the time-varying irregular physical domain that reproduces the complex geometries of coastal regions to a fixed uniform computational one. The advancing of the solution is performed by a second-order accurate strong stability preserving Runge-Kutta fractional-step method in which, at every stage of the method, a predictor velocity field is obtained by the shock-capturing scheme and a corrector velocity field is added to the previous one, to produce a non-hydrostatic divergence-free velocity field and update the water depth. The corrector velocity field is obtained by numerically solving a Poisson equation, expressed in integral contravariant form, by a multigrid technique which uses a four-colour Zebra Gauss-Seidel line-by-line method as smoother. Several test cases are used to verify the dispersion and shock-capturing properties of the proposed model in time-dependent curvilinear grids. [ABSTRACT FROM AUTHOR]

During the late 70' and in the 80', the aluminium bone disease helped to put in the first line the importance of the bone abnormalities in CKD outcomes [[5]]. Since then, the term I renal osteodystrophy i was reserved for the bone histological diagnosis of the CKD-MBD, based on parameters of bone turnover, mineralization and volume. In the late 60' and 70', the measurement of key biochemical parameters such as parathyroid hormone (PTH) became available [[2]], the imaging diagnosis techniques improved [[3]] and the analysis of undecalcified bone became possible to better interpret the bone biopsies [[4]]. Although the diagnosis of CKD-MBD in the current clinical practice is mainly based on non-invasive and worldwide available biochemical and imaging techniques, the gold standard for the diagnosis of CKD bone disease is the bone biopsy. [Extracted from the article]

Purpose: Millions of U.S. households have children who have witnessed intimate partner violence (IPV) between their caregivers. The far-reaching negative influences of IPV on children encompass numerous psychological outcomes and delays in various domains of child development. Given the critical role of self-regulation in cognitive and social functioning, which is necessary for navigating complex social situations and academic success, investigating the impact of IPV on its development is of particular importance. Thus, the objective of this study is to conduct a systematic review of empirical research examining the relationship between IPV exposure and the development of children’s self-regulation.This study systematically reviewed 13 peer-reviewed studies published between 2000 and 2021 that quantitatively examined the effects of IPV exposure on self-regulation in children and adolescents. Studies were found using selected keywords across four scientific databases.Among the 13 studies included in the review, 10 studies identified significant negative effects of IPV exposure on various aspects of self-regulation (i.e., emotional regulation, executive function, and behavioral regulation), and two studies identified indirect pathways through parenting and maternal depression.Previous studies indicate that the normal development of self-regulation in children may be disrupted by stressful and conflict-ridden home environments. Further research is necessary to explore the mechanisms and timing by which IPV exposure influences the development of self-regulation in children, as well as protective factors that may mitigate IPV’s negative effects.Methods: Millions of U.S. households have children who have witnessed intimate partner violence (IPV) between their caregivers. The far-reaching negative influences of IPV on children encompass numerous psychological outcomes and delays in various domains of child development. Given the critical role of self-regulation in cognitive and social functioning, which is necessary for navigating complex social situations and academic success, investigating the impact of IPV on its development is of particular importance. Thus, the objective of this study is to conduct a systematic review of empirical research examining the relationship between IPV exposure and the development of children’s self-regulation.This study systematically reviewed 13 peer-reviewed studies published between 2000 and 2021 that quantitatively examined the effects of IPV exposure on self-regulation in children and adolescents. Studies were found using selected keywords across four scientific databases.Among the 13 studies included in the review, 10 studies identified significant negative effects of IPV exposure on various aspects of self-regulation (i.e., emotional regulation, executive function, and behavioral regulation), and two studies identified indirect pathways through parenting and maternal depression.Previous studies indicate that the normal development of self-regulation in children may be disrupted by stressful and conflict-ridden home environments. Further research is necessary to explore the mechanisms and timing by which IPV exposure influences the development of self-regulation in children, as well as protective factors that may mitigate IPV’s negative effects.Results: Millions of U.S. households have children who have witnessed intimate partner violence (IPV) between their caregivers. The far-reaching negative influences of IPV on children encompass numerous psychological outcomes and delays in various domains of child development. Given the critical role of self-regulation in cognitive and social functioning, which is necessary for navigating complex social situations and academic success, investigating the impact of IPV on its development is of particular importance. Thus, the objective of this study is to conduct a systematic review of empirical research examining the relationship between IPV exposure and the development of children’s self-regulation.This study systematically reviewed 13 peer-reviewed studies published between 2000 and 2021 that quantitatively examined the effects of IPV exposure on self-regulation in children and adolescents. Studies were found using selected keywords across four scientific databases.Among the 13 studies included in the review, 10 studies identified significant negative effects of IPV exposure on various aspects of self-regulation (i.e., emotional regulation, executive function, and behavioral regulation), and two studies identified indirect pathways through parenting and maternal depression.Previous studies indicate that the normal development of self-regulation in children may be disrupted by stressful and conflict-ridden home environments. Further research is necessary to explore the mechanisms and timing by which IPV exposure influences the development of self-regulation in children, as well as protective factors that may mitigate IPV’s negative effects.Conclusions: Millions of U.S. households have children who have witnessed intimate partner violence (IPV) between their caregivers. The far-reaching negative influences of IPV on children encompass numerous psychological outcomes and delays in various domains of child development. Given the critical role of self-regulation in cognitive and social functioning, which is necessary for navigating complex social situations and academic success, investigating the impact of IPV on its development is of particular importance. Thus, the objective of this study is to conduct a systematic review of empirical research examining the relationship between IPV exposure and the development of children’s self-regulation.This study systematically reviewed 13 peer-reviewed studies published between 2000 and 2021 that quantitatively examined the effects of IPV exposure on self-regulation in children and adolescents. Studies were found using selected keywords across four scientific databases.Among the 13 studies included in the review, 10 studies identified significant negative effects of IPV exposure on various aspects of self-regulation (i.e., emotional regulation, executive function, and behavioral regulation), and two studies identified indirect pathways through parenting and maternal depression.Previous studies indicate that the normal development of self-regulation in children may be disrupted by stressful and conflict-ridden home environments. Further research is necessary to explore the mechanisms and timing by which IPV exposure influences the development of self-regulation in children, as well as protective factors that may mitigate IPV’s negative effects. [ABSTRACT FROM AUTHOR]

Current radiological literature is strongly focussed on radiation imaging risks. Indeed, given there is a small but actual augment in cancer risk from exposure to ionizing radiation in children, it is important to understand what the risk of alternative techniques could be. We retrospectively review literature data concerning possible MR imaging risks, focussing on the biological effects of MR, sedation and gadolinium compound risks when dealing with infant patients. The main concerns can be summarized in: (1) Biological effects of non-ionizing electromagnetic fields (EMF) employed—whose mechanisms of interaction with human tissues are polarization, induced current, and thermal heating, respectively. (2) Risks associated with noises produced during MRI examinations. (3) Hazards from ferromagnetic external and/or implanted devices—whose risk of being unintentionally brought inside MR room is higher in children than in adults. (4) Risks associated with sedation or general anaesthesia, essential problem in performing MR in very young patients, due to the exam long-lasting. (5) Risks related to gadolinium-based contrast agents, especially considering the newly reported brain deposition. [ABSTRACT FROM AUTHOR]

This paper presents evidence from a unique reform model that allowed teachers and other educators in a large urban district to collaborate with one another in the development of an innovation meant to improve student ownership and responsibility. In this longitudinal case study, we describe school stakeholders’ learning about the design, the process of knowledge-transfer to school teams, and how school teams shared their ongoing learning with one another. School implementation teams were initially reluctant to share their learning with one another. By engaging in a shared innovation development process with structures for routine sharing, over time, implementation team members were increasingly interested in sharing their learning with one another. We discuss the implications for school improvement efforts. [ABSTRACT FROM AUTHOR]

The last 5 years have witnessed growing support amongst government institutions and educational foundations for applying continuous improvement research (CIR) in school settings. CIR responds to the challenge of implementing effective educational innovations at scale by working with practitioners in local contexts to understand 'what works, for whom, and under what conditions.' CIR works to achieve system improvement through the use of plan-do-study-act (PDSA) cycles, which are multiple tests of small changes. This comparative case study of two urban school districts examined how innovation design teams took up PDSA in their work to improve high school student outcomes, and their perceptions of PDSA as an approach to innovation development, adaptation, and implementation. Findings revealed both possibilities and challenges for implementing PDSA. Nearly all participants reported the value in PDSA, and participants pointed to connections to previous experiences and PDSA training as helping to build capacity. However, we found mixed levels of enthusiasm for actually conducting PDSA cycles, and capacity constraints regarding time and data collection. [ABSTRACT FROM AUTHOR]

Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned. [ABSTRACT FROM AUTHOR]

In this paper a new finite-volume non-hydrostatic and shock-capturing three-dimensional model for the simulation of wave-structure interaction and hydrodynamic phenomena (wave refraction, diffraction, shoaling and breaking) is proposed. The model is based on an integral formulation of the Navier-Stokes equations which are solved on a time dependent coordinate system: a coordinate transformation maps the varying coordinates in the physical domain to a uniform transformed space. The equations of motion are discretized by means of a finite-volume shock-capturing numerical procedure based on high order WENO reconstructions. The solution procedure for the equations of motion uses a third order accurate Runge-Kutta (SSPRK) fractional-step method and applies a pressure corrector formulation in order to obtain a divergence-free velocity field at each stage. The proposed model is validated against several benchmark test cases. [ABSTRACT FROM AUTHOR]

On 5 July 2014, an eruptive fissure opened on the eastern flank of Etna volcano (Italy) at ~3.000 m a.s.l. Strombolian activity and lava effusion occurred simultaneously at two neighbouring vents. In the following weeks, eruptive activity led to the build-up of two cones, tens of meters high, here named Crater N and Crater S. To characterize the short-term (days) dynamics of this multi-vent system, we performed a multi-parametric investigation by means of a dense instrumental network. The experimental setup, deployed on July 15-16th at ca. 300 m from the eruption site, comprised two broadband seismometers and three microphones as well as high speed video and thermal cameras. Thermal analyses enabled us to characterize the style of eruptive activity at each vent. In particular, explosive activity at Crater N featured higher thermal amplitudes and a lower explosion frequency than at Crater S. Several episodes of switching between puffing and Strombolian activity were noted at Crater S through both visual observation and thermal data; oppositely, Crater N exhibited a quasi-periodic activity. The quantification of the eruptive style of each vent enabled us to infer the geometry of the eruptive system: a branched conduit, prone to rapid changes of gas flux accommodated at the most inclined conduit (i.e. Crater S). Accordingly, we were able to correctly interpret acoustic data and thereby extend the characterization of this two-vent system. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis represents a significant and increasing healthcare burden in Europe, but most patients at increased risk of fracture do not receive medication, resulting in a large treatment gap. Identification of patients who are at particularly high risk will help clinicians target appropriate treatment more precisely and cost-effectively, and should be the focus of future research. Introduction: The purpose of the study was to review data on the identification and treatment of patients with osteoporosis at increased risk of fracture. Methods: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review current data on the epidemiology and burden of osteoporosis and the patterns of medical management throughout Europe. Results: In Europe in 2010, the cost of managing osteoporosis was estimated at €37 billion and notably the costs of treatment and long-term care of patients with fractures were considerably higher than the costs for pharmacological prevention. Despite the availability of effective treatments, the uptake of osteoporosis therapy is low and declining, in particular for secondary fracture prevention where the risk of a subsequent fracture following a first fracture is high. Consequently, there is a significant treatment gap between those who would benefit from treatment and those who receive it, which urgently needs to be addressed so that the burden of disease can be reduced. Conclusions: Implementation of global fracture prevention strategies is a critical need. Future research should focus on identifying specific risk factors for imminent fractures, periods of high fracture risk, patients who are at increased risk of fracture and therapies that are most suited to such high-risk patients and optimal implementation strategies in primary, secondary and tertiary care. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) successfully prevents allograft rejection, but nephrotoxicity is still a dose-limiting adverse effect. TLR4 activation promotes kidney damage but whether this innate immunity receptor mediates CsA nephrotoxicity is unknown. The in vivo role of TLR4 during CsA nephrotoxicity was studied in mice co-treated with CsA and the TLR4 inhibitor TAK242 and also in TLR4 mice. CsA-induced renal TLR4 expression in wild-type mice. Pharmacological or genetic targeting of TLR4 reduced the activation of proinflammatory signaling, including JNK/c-jun, JAK2/STAT3, IRE1α and NF-κB and the expression of Fn14. Expression of proinflammatory factors and cytokines was also decreased, and kidney monocyte and lymphocyte influx was prevented. TLR4 inhibition also reduced tubular damage and drastically prevented the development of kidney fibrosis. In vivo and in vitro CsA promoted secretion of the TLR ligand HMGB1 by tubular cells upstream of TLR4 activation, and prevention of HMGB1 secretion significantly reduced CsA-induced synthesis of MCP-1, suggesting that HMGB1 may be one of the mediators of CsA-induced TLR4 activation. These results suggest that TLR4 is a potential pharmacological target in CsA nephrotoxicity. [ABSTRACT FROM AUTHOR]

From January 2011 to December 2015, Mt. Etna was mainly characterized by a cyclic eruptive behavior with more than 40 lava fountains from New South-East Crater. Using the RMS (Root Mean Square) of the seismic signal recorded by stations close to the summit area, an automatic recognition of the different states of volcanic activity (QUIET, PRE-FOUNTAIN, FOUNTAIN, POST-FOUNTAIN) has been applied for monitoring purposes. Since values of the RMS time series calculated on the seismic signal are generated from a stochastic process, we can try to model the system generating its sampled values, assumed to be a Markov process, using Hidden Markov Models (HMMs). HMMs analysis seeks to recover the sequence of hidden states from the observations. In our framework, observations are characters generated by the Symbolic Aggregate approXimation (SAX) technique, which maps RMS time series values with symbols of a pre-defined alphabet. The main advantages of the proposed framework, based on HMMs and SAX, with respect to other automatic systems applied on seismic signals at Mt. Etna, are the use of multiple stations and static thresholds to well characterize the volcano states. Its application on a wide seismic dataset of Etna volcano shows the possibility to guess the volcano states. The experimental results show that, in most of the cases, we detected lava fountains in advance. [ABSTRACT FROM AUTHOR]

In this paper we propose a new model based on a contravariant integral form of the fully non-linear Boussinesq equations (FNBE) in order to simulate wave transformation phenomena, wave breaking, runup and nearshore currents in computational domains representing the complex morphology of real coastal regions. The above-mentioned contravariant integral form, in which Christoffel symbols are absent, is characterized by the fact that the continuity equation does not include any dispersive term. The Boussinesq equation system is numerically solved by a hybrid finite volume-finite difference scheme. A high-order upwind weighted essentially non-oscillatory (WENO) finite volume scheme that involves an exact Riemann solver is implemented. The wave breaking is represented by discontinuities of the weak solution of the integral form of the non-linear shallow water equations (NSWE). On the basis of the shock-capturing high order WENO scheme a new procedure, for the computation of the structure of the solution of a Riemann problem associated with a wet/dry front, is proposed in order to simulate the run up hydrodynamics in swash zone. The capacity of the proposed model to correctly represent wave propagation, wave breaking, run up and wave induced currents is verified against test cases present in literature. The results obtained are compared with experimental measures, analytical solutions or alternative numerical solutions. The proposed model is applied to a real case regarding the simulation of wave fields and nearshore currents in the coastal region opposite San Mauro Cilento (Italy). [ABSTRACT FROM AUTHOR]

There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD ( n = 49) with those who underwent HTx ( n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication ( n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe. [ABSTRACT FROM AUTHOR]

The existence of a workforce crisis in behavioral health has been recognized for decades. However, workforce problems often have been viewed as too large, too complex, and too daunting for individual states to tackle. This article reviews the progress of one state in systematically strengthening its workforce as part of a federally supported effort to transform mental health services. The workforce priorities in Connecticut are identified and the specific workforce transformation projects and their impact are described. The success in sustaining these initiatives after cessation of federal support is reviewed. The authors conclude by offering five recommendations to guide comprehensive state workforce development. This work has particular salience for the many states across the nation that have identified behavioral health service and workforce needs as obstacles to comprehensive health care reform. [ABSTRACT FROM AUTHOR]