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Employing a novel control function regression method that accounts for the endogenous matching of banks and executives, we find that equity portfolio vega, the sensitivity of executives’ equity portfolio value to their firms’ stock return volatility, leads to systemic risk that manifests during subsequent economic contractions but not expansions. We further find that vega encourages systemically risky policies, including maintaining lower common equity Tier 1 capital ratios, relying on more run-prone debt financing, and making more procyclical investments. Collectively, our evidence suggests that executives’ incentive-compensation contracts promote systemic risk-taking through banks’ lending, investing, and financing practices.

Limited data are available on the use of the prone position in cardiac surgery. Concerns in performing this maneuver in open cardiac surgery due to the risk of post-sternotomy wound infections and hemodynamic instability do not seem to be supported by existing evidence. Indeed, available data show that prone positioning may improve gas exchange in cardiac surgery patients as well. However, previous studies of prone positioning in this setting were heterogeneous in patient characteristics and outcomes evaluated. As a result, whether prone positioning also may be effective in reducing mortality in patients with postoperative acute respiratory failure, particularly in those who underwent surgery under extracorporeal circulation, remains to be clearly elucidated. The aim of this article is to provide an overview of available literature, which seems to suggest the efficacy of prone positioning, and to make an in-depth analysis of the studies on this topic by evaluating the efficacy of this maneuver on hard endpoints.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Objectives Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. Methods This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox’s regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. Results In the derivation cohort, the median age was 69 (IQR, 58–77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59–77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253–2.418], p p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796–0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758–0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). Conclusion Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. Key Points •Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. •Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. •The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Malignant melanoma (MM) is a highly aggressive neoplasm with a growing worldwide incidence. It is not uncommon that the disease is already metastatic at the time of the first diagnosis. Regional lymph nodes and skin are the first and most common metastatic sites, followed by distant visceral sites (lungs, liver, and central nervous system) and bone. In this clinical setting, fine-needle aspiration (FNA) often represents the first diagnostic approach. FNA is a useful tool to obtain a rapid and accurate diagnosis, in conjunction with ancillary techniques and molecular analysis, as recommended by recent guidelines. The aim of this review was to describe the cytomorphology, immunocytochemical tools, and molecular tools used for the diagnosis of MM metastases on FNA.

The aim of this study is to compare the efficacy of single-point injection of botulinum toxin A versus multi-point operative protocols found in the literature in reducing hypertrophy in patients with masticatory muscle hypertrophy. A systematic review was performed in accordance with the Park et al., 2018 guidelines, selecting articles from PubMed, Google Scholar, Web of Science and Ovid databases up to July 8, 2020.28 studies met the eligibility criteria. 748 patients were treated for masseter hypertrophy (MH) and 4 patients for temporal muscle hypertrophy. As for MH: in 45.2% of cases 3 injection sites (IS) were used, in 18.8% 1 IS, in 16.2% 2 IS, in 13% 5 IS, in 4.1% 6 IS, 2.7% 4 IS. At three months, the mean reduction in masseter muscle thickness is 26–31% when 1 IS was used, 28% in 2 IS, 12–27% in 3 IS and 22–30% in 6 IS. Heterogeneity of results, high bias level and selective reports led to a difficult efficacy comparison of the injection techniques described. Data suggest that the lowest number of IS possible should be used until stronger evidences are presented. Homogeneity in pre- and post-operative protocols is needed to establish a reliable setting for the condition under study.

Since COVID-19 has emerged as a word public health problem, attention has been focused on how immune suppressive drugs used for the treatment of autoimmune disorders influence the risk for SARS-CoV-2 infection and the development of the acute respiratory distress syndrome (ARDS). Here we discuss the disease-modifying agents approved for the treatment of multiple sclerosis (MS) within this context. Interferon (IFN)-1a and -1b, which display antiviral activity, could be protective in the early stage of COVID-19 infection, although SARS-CoV-2 may have developed resistance to IFNs. However, in the hyper inflammation stage, IFNs may become detrimental by facilitating macrophage invasion in the lung and other organs. Glatiramer acetate and its analogues should not interfere with the development of COVID-19 and may be considered safe. Teriflunomide, a first-line oral drug used in the treatment of relapsing-remitting MS (RRMS) may display antiviral activity by depleting cellular nucleotides necessary for viral replication. The other first-line drug, dimethyl fumarate, may afford protection against SARS-CoV-2 by activating the Nrf-2 pathway and reinforcing the cellular defences against oxidative stress. Concern has been raised on the use of second-line treatments for MS during COVID-19 pandemic. However, this concern is not always justified. For example, fingolimod, might be highly beneficial during the hyperinflammatory stage of COVID-19 for a number of mechanisms including the reinforcement of the endothelial barrier. Caution is suggested for the use of natalizumab, cladribine, alemtuzumab, and ocrelizumab, although MS disease recurrence after discontinuation of these drugs may overcome a potential risk for COVID-19 infection.

Background and aims Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. Methods and results This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p, Graphical abstract Image 1

Oliguric acute kidney injury due to traumatic rhabdomyolysis can be potentially lethal if the proper medical therapy combined with extracorporeal detoxification is not performed. Different extracorporeal techniques are available to overcome this syndrome. Here, we report the first case of removal of myoglobin and successful recovery from acute kidney injury in an elderly septic patient using supra-hemodiafiltration with endogenous reinfusion technique (HFR-Supra) combined with the medical therapy.

The International Natural Product Sciences Taskforce: et al., Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities., A.C. and E.I. thank the Ministerio de Ciencia, Innovación y Universidades, Spain (Project AGL2017-89417-R) for support. F.A.M. acknowledges the support by Ministerio de Economia y Competitividad, Spain (project AGL2017-88083-R).

Introduction: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD), but the underlying pathological mechanism has not been fully understood. Voxel-based morphometry could be used to evaluate regional atrophy and its relationship with cognitive performances in early PD-MCI. Patients and Methods: One hundred and six patients with PD were recruited from a larger cohort of patients, the Parkinson’s Disease Cognitive Impairment Study (PaCoS). Subject underwent a T1-3D MRI and a complete clinical and neuropsychological evaluation. Patients were divided into PD with normal cognition (PD-NC) and PD-MCI according to the MDS level II criteria–modified for PD-MCI. A subgroup of early patients with short disease duration (≤ 2years) was also identified. VBM analysis between PD-NC and PD-MCI and between early PD-NC and PD-MCI was performed using two-sample t tests with whole-brain statistical threshold of p < 0.001 uncorrected in the entire PD group and p < 0.05 FWE inside ROIs, in the early PD. Results: Forty patients were diagnosed with MCI and 66 were PD-NC. PD-MCI patients showed significant gray matter (GM) reduction in several brain regions, including frontal gyrus, precuneus, angular gyrus, temporal lobe, and cerebellum. Early PD-MCI showed reduction in GM density in superior frontal gyrus and cerebellum. Moreover, correlation analysis between neuropsychological performances and GM volume of early PD-MCI patients showed associations between performances of Raven and superior frontal gyrus volume, Stroop time and inferior frontal gyrus volume, accuracy of Barrage and volume of precuneus. Conclusion: The detection of frontal and cerebellar atrophy, even at an early stage, could be used as an early marker of PD-related cognitive impairment.

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4 years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches.

Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.

Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are differentiated by the time of onset of cognitive and motor symptoms (‘1-year rule’). We explored the neuropsychological continuum of DLB and PDD subjects with different timing of dementia onset. Objective: Our aim was to compare the neuropsychological profile of DLB and PDD patients with different timing of dementia onset. Methods: Neuropsychological findings at the diagnosis of dementia of 66 PDD and 42 DLB patients were retrospectively compared. Patients with PDD were divided into three tertile subgroups according to the time interval between the onset of parkinsonism and dementia (N = 24, 2–4 years; N = 17, 5–7 years; N = 25 ≥8 years, respectively). Results: DLB patients performed worse on the Stroop and semantic fluency tests than PDD, even in comparison to PD with early dementia onset. No significant differences among PDD subgroups were reported. Conclusion: Executive and semantic language tests could differentiate DLB and PD patients with earlier development of dementia relative to parkinsonism.

Summary Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severely impacted the management of critically ill patients, including nutritional therapy. This study aimed to verify an association between mortality and the energy and protein provided to critically ill patients affected by the SARS-CoV-2 and receiving enteral nutrition support. Methods Patients with confirmed COVID-19, with >7 days of stay in the ICU, on enteral nutrition were followed from the moment of hospitalization until discharge from the ICU or death. Data about age, gender, Simplified Acute Physiology Score III (SAPS3), intensive care unit (ICU) length of stay, days on mechanical ventilation (MV), clinical endpoint outcome (discharge or death), and daily energy and protein provision were collected from electronic medical records. Cox regression analyses and Kaplan-Meyer curves were used in statistical analysis. Results Fifty-two patients (66.2 ± 13.1 years; 53.8% women) were enrolled in the present study. The mean length of hospitalizations and SAPS3 score were 17.8 ± 9.8 days and 78.7 ± 14.7, respectively; all patients needed mechanical ventilation (mean of days was 16.42 ± 9.1). For most patients (73.1%) the endpoint was death. Twenty-five percent of patients had protein supply >0.8 g/IBW/day. Survival during COVID-19 hospitalization at ICU was significantly different among patients according to protein supply (p = 0.005). Hazard Ratios (HR) for protein supply showed that a protein intake >0.8 g/IBW/day was associated with significantly lower mortality (HR 0.322, p = 0.049). Conclusion Our study suggests that a protein supply at least > 0.8 g/IBW/day could be related to reduced mortality in ICU patients with COVID-19.

BACKGROUND To show a novel modified technique to perform minimally invasive anterior odontoid screw fixation. METHODS Twenty-nine patients with a mean age of 45 years were treated with a modified percutaneous anterior odontoid screw fixation. All patients were affected by Type II or rostral shallow Type III odontoid fractures. A modified guide tube was used in all these patients, with reduction of soft tissue dissection for percutaneous approach. RESULTS There were no complications related to the modified technique. Good results and optimal screw placement were achieved in 28 out of 29 patients. Only in 1 patient we observed, after mobilization, screw displacement, probably due to severe osteoporosis. CONCLUSIONS In our opinion, this modified percutaneous minimally invasive technique for anterior odontoid screw fixation, along with the use of a soft tissue dilator not fixed to the spine, has not yet been reported in literature and is strongly recommended to reduce invasiveness of odontoid screw placement.

Epigenetic-sensitive mechanisms, mainly DNA methylation, mirror the relationship between environmental and genetic risk factors able to affect the sensitiveness to development of obesity and its comorbidities. Bariatric and metabolic surgery may reduce obesity-related cardiovascular risk through tissue-specific DNA methylation changes. Among the most robust results, differential promoter methylation of ACACA, CETP, CTGF, S100A8, and S100A9 genes correlated significantly with the levels of mRNA before and after gastric bypass surgery (RYGB) in obese women. Additionally, promoter hypermethylation of NFKB1 gene was significantly associated with reduced blood pressure in obese patients after RYGB suggesting useful non-invasive biomarkers. Of note, sperm-related DNA methylation signatures of genes regulating the central control of appetite, such as MC4R, BDNF, NPY, and CR1, and other genes including FTO, CHST8, and SH2B1 were different in obese patients as compared to non-obese subjects and patients who lost weight after RYGB surgery. Importantly, transgenerational studies provided relevant evidence of the potential effect of bariatric and metabolic surgery on DNA methylation. For example, peripheral blood biospecimens isolated from siblings born from obese mothers before bariatric surgery showed different methylation signatures in the insulin receptor and leptin signaling axis as compared to siblings born from post-obese mothers who underwent surgery. This evidence suggests that bariatric and metabolic surgery of mothers may affect the epigenetic profiles of the offspring with potential implication for primary prevention of severe obesity. We update on tissue-specific epigenetic signatures as potential mechanisms underlying the restoration of metabolic health after surgery suggesting useful predictive biomarkers.

Orthognathic surgery and the Le Fort I osteotomy result in noticeable alterations to the nasal/nasolabial anatomy. The alar base cinch technique is a surgical technique to control lateralization of the base of the nose and is well described in the literature. The aim of this scoping review was to identify every unique alar cinch suture technique reported in orthognathic surgery and to propose a classification for the different techniques described. A search was conducted in the PubMed, Cochrane Library, and Scopus electronic databases covering the period May 1980 to July 2020, which identified 10 articles that were eligible for this review. Among these, there were several proposals for modifications to the technique, and different studies to show the effectiveness of one type among all others. Despite observing multiple techniques and variations of these while performing this review, the lack of a classification for alar cinch suture was noticed. Therefore, we propose a classification of the alar cinch suture that includes four types, which cover all of the cinching techniques described. It is believed that the use of a standardized classification may be useful to avoid duplicate publishing of techniques and to set a standard for further studies.

Puberty represents a milestone during a person's life and is characterized by several physical and psychological changes which end with the achievement of sexual maturation and of fertility. Puberty onset depends on a series of sophisticated, not completely understood, mechanisms certainly involving Gonadotropin-Releasing Hormone (GnRH) and its effects on pituitary gonadotropins. As recent evidence has demonstrated that pubertal timing deeply affects future adult health life, many efforts have been performed in order to clarify the exact actors involved in the onset and progression of puberty. Genetic factors are undoubtedly essential players in the regulation of pubertal development, accounting for approximately 50-80% of its variability. Mutations in genes such as KISS1, MKRN3, and DLK1 have been associated with central precocious puberty. Interestingly, a possible involvement of epigenetic mechanisms has been proposed as additional element able to affect pubertal phase. Environmental factors have recently attracted much attention. Indeed, an overall decrease in the age of puberty has been observed in the last decades. As genetic factors require long time to exert their effect, other players, such as environmental ones, may be involved. Special focus has been posed on nutritional status, endocrine-disrupting chemicals with non-conclusive results. Pubertal timing deeply affects future life, suggesting the need to clarify mechanisms driving pubertal onset and progression, in order to identify tailored therapeutic strategies and targets.

Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder caused by mutations in the PKLR gene. PKD is characterized by non-spherocytic hemolytic anemia of variable severity and may be fatal in some cases during early childhood. Although not considered the standard of care, allogeneic stem cell transplantation has been shown as a potentially curative treatment, limited by donor availability, toxicity, and incomplete engraftment. Preclinical studies were conducted to define conditions to enable consistent therapeutic reversal, which were based on our previous data on lentiviral gene therapy for PKD. Improvement of erythroid parameters was identified by the presence of 20%–30% healthy donor cells. A minimum vector copy number (VCN) of 0.2−0.3 was required to correct PKD when corrected cells were transplanted in a mouse model for PKD. Biodistribution and pharmacokinetics studies, with the aim of conducting a global gene therapy clinical trial for PKD patients (RP-L301-0119), demonstrated that genetically corrected cells do not confer additional side effects. Moreover, a clinically compatible transduction protocol with mobilized peripheral blood CD34+ cells was optimized, thus facilitating the efficient transduction on human cells capable of repopulating the hematopoiesis of immunodeficient mice. We established conditions for a curative lentiviral vector gene therapy protocol for PKD., Graphical abstract, We have established safe transduction conditions of human hematopoietic stem and progenitors cells (HSPCs) using a therapeutic lentiviral vector to correct pyruvate kinase deficiency (PKD). Lentiviral transduction protocol efficiently corrects HSPCs without affecting engraftment properties. This protocol is being applied to a gene therapy clinical trial for PKD patients.

Over the last decades, interest toward athlete’s heart has progressively increased, leading to improve the knowledge on exercise-induced heart modifications. Sport may act as a trigger for life-threatening arrhythmias in patients with structural or electrical abnormalities, hence requiring to improve the diagnostic capability to differentiate physiological from pathological remodeling. Pathological alterations are often subtle at the initial stages; therefore, the challenge is to promptly identify athletes at risk of sudden cardiac death during the pre-participation screening protocols. Advanced imaging modalities such as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) can non-invasively depict coronary vessels and provide a deep morpho-functional and structural characterization of the myocardium, in order to rule out pathological life threatening alterations, which may overlap with athletes’ heart remodeling. The purpose of the present narrative review is to provide an overview of most frequent diagnostic challenges, defining the boundaries between athlete's heart remodeling and pathological structural alteration with a focus on the role and importance of CCTA and CMR.

Um mapeamento da cobertura florestal e dos diferentes usos da terra proporciona informações fundamentais para a gestão territorial visando ao desenvolvimento social e econômico, planejamento e controle ambiental e proteção dos recursos naturais. Neste artigo, é apresentado um novo mapeamento, valendo-se de sinergias entre os dados de campo do Inventário Florístico Florestal de Santa Catarina (IFFSC) e o uso de recursos de sensoriamento remoto. Imagens do satélite Landsat-8 OLI do ano de 2017 foram classificadas, utilizando o algoritmo Random Forest. A legenda é composta por 12 classes temáticas; a área mínima mapeada é de 0,5 hectare. O mapa tem acurácia geral de 95%, com intervalo de confiança de 1,0% (alfa=0,05). A acurácia média por classe varia entre 90% (agricultura) e 97% (restinga). Para a classe floresta, o mapa apresentou coincidência de 96,2% com os pontos amostrais do IFFSC. A cobertura florestal nativa (florestas a partir do estágio médio de regeneração) está presente em 38,05% do território, reflorestamentos em 10,46%, agricultura em 16,73% (incluídos 1,77% de culturas de arroz irrigado), pastagens e campos naturais em 29,24%. A área da extensão original da restinga foi determinada em 1.773km², dos quais 814,5km² (ou 45,9%) cobertos por remanescentes naturais, praias e dunas. O mapeamento constitui a base para a tomada de decisão de agentes públicos envolvidos em atividades de planejamento e gestão territorial e servirá como linha-base para o monitoramento contínuo da extensão da cobertura florestal do estado.

Auditor credibility is important in the banking industry due to the opacity of bank assets and the use of financial statements by external parties to facilitate monitoring. Depositors monitor and discipline bank behavior, but they can also contribute to the spread of shocks from one bank to another. We argue that depositors perceive bank failure as an audit failure, which reduces their assessment of auditor credibility. We document that exposure to failure through the audit firm is associated with lower uninsured deposit growth following the failure, consistent with depositors perceiving failures as a negative signal of auditor credibility. We further document that this association is stronger when depositors perceive connection to failure to reflect a pervasive issue within the audit firm. Collectively, our results suggest that depositors consider accounting signals at other banks in assessing financial reporting credibility. JEL Classifications: G21; M41; M42.

Necrotizing enterocolitis is one of the most frequent and severe gastrointestinal diseases that affect preterm newborns in Neonatal Intensive Care Units. It was firstly described in 1960s, but this clinical entity was not widely recognized until the advent of modern neonatal intensive care. The disease is characterized by submucosal edema, infiltration of intestinal wall by immune cells, specifically neutrophils and, in severe forms, wall necrosis that leads to intestinal perforation. Its incidence is inversely associated to birth weight and gestational age. Necrotizing enterocolitis has been responsible for high rates of morbidity and mortality (15-30%), despite improvements made in neonatal care in the last decades. The challenge is to optimize strategies for early diagnosis, define the best medical and surgical treatments and standardize preventive measures. Several biomarkers have been proposed for the early prediction of necrotizing enterocolitis onset in preterm newborns and can be useful not only for diagnostic purposes but also for prediction of disease progression and severity. The purpose of this paper is to illustrate the most recent evidence regarding the diagnosis and prevention of necrotizing enterocolitis. This manuscript contributes to clinical decision-making in preterm neonates at high risk of developing necrotizing enterocolitis.

The modeling of battery electric vehicles (BEVs) still represents a challenge for vehicle manufacturers. The installation of the new types of components needed for BEVs gives rise to uncertainties in the quantification of parameters like the vehicle's weight. Indeed, vehicle weight plays a key role, since it has a drastic effect on the vehicle's range, which is an important selling point for BEVs. Uncertainties in weight estimation create weight fluctuations during the early development phase and the need to resize components like the electric machine or battery. This in turn affects the components' volume and weight. However, such resizing can also lead to component collision and unfeasibility of the vehicle architecture. To solve this problem and to support concept engineers during the early development phase, an iterative approach is required that is capable of estimating weight and volume fluctuations in the relevant components. The approach should also consider the geometrical interdependencies of the components, to ensure that no collisions occur between them. Taking the gearbox as an example application, this paper presents a novel approach that satisfies these requirements.

Numerical and experimental analyses regarding the dynamic behavior of an onboard rotor are presented in this work. Aircraft engines, rotating machines placed in offshore petroleum boards, automotive engines, helicopter rotors, and offshore wind turbines are typical examples of onboard rotating machines. Therefore, in the present contribution, a finite element method is used to formulate the differential equations of motion associated with the considered onboard rotor system. The model is based on the kinetic and strain energies of the shaft, kinetic energy of the discs and mass unbalance, and the virtual work associated with the external forces, as well as the stiffness and damping coefficients of the bearings. A rotating machine composed of a flexible horizontal shaft, one rigid disc, and supported by two self-alignment ball bearings is studied. The numerical and experimental vibration responses of the rotor subjected to impulse and sinusoidal base excitations are compared. Different analyses are performed both in the time and frequency domains. The obtained results demonstrated that the model is capable of capturing the dynamic behavior of the onboard rotor satisfactorily.

In February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8–4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7–100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0–28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2–36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression., Vo’, Italy, is a unique setting for studying SARS-CoV-2 antibody dynamics because mass testing was conducted there early in the pandemic. Here, the authors perform two follow-up serological surveys and estimate seroprevalence, the extent of within-household transmission, and the impact of contact tracing.

Introduction Retinal impairment has previously been described in Parkinson's Disease (PD), also in early stage of disease. Idiopathic Rapid-eye-movement sleep Behavior Disorder (iRBD) is considered the strongest marker in the diagnosis of “Prodromal PD”. Thus, we evaluated the thickness of retinal layers and the microvascular retinal pattern in a group of iRBD patients compared to PD and healthy subjects (HCs). Methods retinal layer's thickness and microvascular pattern among PD, iRBD and HCs were assessed using Spectral-Density Optical Coherence Tomography (SD-OCT) and OCT-Angiography (OCT-A), respectively. Results Forty-one eyes from 21 PD, 37 eyes from 19 iRBD and 33 eyes from 17 HCs were analysed. Peripapillary Retinal Nerve Fiber Layer (RNFL) was thinner in PD and RBD compared to HCs. All macular retinal layers, except for retinal pigment epithelium, resulted to be significantly thinner in iRBD and in PD compared to HCs, also adjusting by age, sex and hypertension. Macular RNFL and ganglionic cell layer were thinner in PD compared to iRBD. Moreover, in iRBD, a peculiar microvascular pattern was found, characterized by a higher vascularization of the deep capillary plexus with respect both PD patients and HCs. Conclusion in PD and iRBD patients retina was thinner than HCs, and values of iRBD were between PD and HCs. Moreover, in iRBD, a peculiar microvascular pattern has been found, characterized by a higher vascularization of the deep capillary plexus. Our findings suggest that retina might be considered a biomarker of neurodegeneration in iRBD, easily estimable using non-invasive tool such as OCT and OCT-A.

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson’s disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson’s Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD.

Background Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson’s disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. Methods Parkinson’s disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. Results Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41–11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76–32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86–9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. Conclusion Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

Background: With the use of non-objective measurement, adherence to growth hormone (GH) therapy has been reported suboptimal in a large proportion of patients, and poor adherence has been shown to affect short-term growth response in patients receiving GH treatment. Objective: The Easypod™ electronic device allows objective measurement of adherence. In this study, we report 3-year prospective adherence data of the Italian cohort of naïve GH deficient (GHD) children extrapolated from the Easypod Connect Observational Study (ECOS) database. Patients and methods: Seventy-three GHD children naïve to GH treatment were included in the analysis. 22 Italian centers participated in the study. Results: Mean adherence rate was consistently above 85% across the 3-year observation period. Particularly, mean adherence was 88.5%, 86.6%, and 85.7% after 1, 2 and 3years, respectively. Mean (± SD) height-SDS increase after the first year was 0.41 (± 0.38). Conclusions: The majority of naïve GHD children starting GH treatment with Easypod maintained an adherence rate > 85% up to 3years. Easypod is a useful tool to follow-up patients’ adherence allowing timely intervention to improve optimal treatment for these patients.

Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.

Background: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. Objectives: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterraneanstyle diet on indices of inflammation and changes in nutritional status. Methods: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65–79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. Results: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. Conclusions: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. Am J Clin Nutr 2019;00:1–12.

To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3 months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. Patients were 230 (females 66.1%; mean age 38 years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6 months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.

Background: Roy-Camille reported only three patients in their Type 3 posttraumatic transverse sacral fracture (TSF) classification. A modified Roy-Camille classification has been already proposed by other authors suggesting further categorization of the TSFs as partially displaced or completely displaced to predict the rate of neurological recovery following lumbopelvic fixation. Materials and Methods: We reported three adult cases of surgical fixation of fracture–dislocation (3A and 3B) of the sacrum due to traumatic injuries and submitted to lumbopelvic posterior reconstruction. A case of a 15-year-old male patient affected by Type 3C with vascular pelvic injury was also reported. A comprehensive literature search was performed on evaluation and management of Type 3 TSFs. Results: In Type 3A, there is a minimal anterior dislocation and the reduction is feasible with good chance of recovery. In Type 3B, the anterior dislocation is severe, neurological deficits are present, reduction is difficult, and there is a risk of vascular injury both at the trauma and during the surgical reduction. In Type 3C, the anterior dislocation is massive, and the risk of vascular injury is very high requiring prompt vascular or endovascular treatment. Open reduction and posterior instrumentation are technically feasible in patients affected by Type 3 high TSFs. Conclusions: In our opinion, a modified Roy-Camille classification could be useful in the assessment of prognostic and therapeutic aspects of such fractures, In our opinion, a modified Roy-Camille classification could help assess the prognostic and therapeutic aspects of such fractures, in which the severity of the dislocation affects the surgical technique, the chance of neurological recovery, and the patient's life expectancy.

The peculiar combined, or binary involvement of epithelium and stroma makes basal cell carcinoma (BCC) a unique tumour. Nerve fibres have been shown to play an active role in different cancers. A prospective observational study was carried out on punch biopsies harvested within BCC surgical excision specimens. A total of 10 samples of histologically diagnosed BCC, derived from 10 different patients (five females, five males), was included in the study. Within the BCCs, seven different histological sub-types were identified: morphea-like, basosquamous, micronodular, mixed nodular-micronodular, adenoid, nodular and superficial multifocal. Nerve fibres were stained for indirect immunofluorescence targeting protein gene product 9.5. Three different morphological patterns of nerve fibre distribution within the BCCs were identified. Pattern 1 displayed a normal skin nerve pattern, in which the fibres were dislodged by the growing tumour masses. Pattern 2 featured a ball of curved, tangled nerve fibres close to the tumour masses, slightly resembling piloneural collar nerve fibres, wrapped around hair follicles in the normal anatomical setting. Pattern 3 showed nerve fibres crowding in the sub-epidermal layer with focal epidermal hyperinnervation. Such a pattern is reminiscent of the typical anatomical neuro-epithelial interaction in mechanosensory organs. Our study may disclose a hidden third player, of nerves. Thus, tissue involvement of BCCs may be better represented by the triad of epithelium, stroma and nerves, each component retaining some features associated with its developmental setting.

Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as "natural gene therapy" in patients with FA, we sought to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30-year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB-chromosomal breakage test. Relative to non-mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub-cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non-mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long-term clinical outcomes.

BACKGROUND/OBJECTIVES Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity. SUBJECTS/METHODS Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex. RESULTS There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p

Objetivo: avaliar o nivel de estresse ambiental e a qualidade de vida de perfusionistas brasileiros. Metodo: trata-se de uma pesquisa quantitativa com delineamento transversal com perfusionistas brasileiros em situacao ativa. Os instrumentos de pesquisa compreenderam o inventario de estresse em enfermeiros adaptado e a escala Short Form Health Survey . Resultados: a analise do fator papeis estressores da carreira apresentou diferenca significativa entre os profissionais com carga horaria semanal de ate 30 horas e 30 a 40 horas ( p =0,005). Entre os dois grupos observou-se que o profissional que trabalha menos que 30 horas (26,56 ± 7,04) tem nivel inferior de estresse em relacao ao grupo que trabalha entre 30 e 40 horas (31,31 ± 8,14; p = 0,005). Na qualidade de vida a media do componente fisico foi de 71,53 ± 18,49 e do componente mental 61,53 ± 15,85. Os profissionais com idade superior a 50 anos apresentam qualidade de vida inferior as demais faixas etarias ( p = 0,03). Conclusao : os perfusionistas com baixo nivel de estresse apresentam qualidade de vida superior quando comparados aos com nivel de estresse elevado.

Background The treatment of esophagogastric junction outflow obstruction (EGJOO) currently mirrors that of achalasia, but this is based on only a few studies on small case series. The aim of this prospective, controlled study was to assess the outcome of laparoscopic Heller-Dor (LHD) in patients with EGJOO, as compared with patients with esophageal achalasia. Materials and Methods Between 2016 and 2019, patients with manometric diagnosis of idiopathic EGJOO and patients with radiological stage I achalasia, both treated with LHD, were compared. The achalasia group was further analyzed by subgrouping the patients based on the manometric pattern. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score > 3 or the need for retreatment. Results During the study period, 150 patients were enrolled: 25 patients had EGJOO and 125 had radiological stage I achalasia (25 pattern I, 74 pattern II, and 26 pattern III). The median follow-up was 24 months (IQR: 34–16). Treatment was successful in 96% of patients in the EGJOO group and in 96% of achalasia patients with pattern I, 98.7% in those with pattern II, and 96.2% of those with pattern III (p=0.50). High-resolution manometry showed a reduction in the LES resting pressure and integrated relaxation pressure for all patients in all 4 groups (p Conclusion This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. LHD emerged as an effective treatment for EGJOO, with an excellent success rate, comparable with the procedure’s efficacy in treating early-stage achalasia.

Eyelid closing or opening disorders have been only sporadically described in patients with focal brain lesions over the last decades. Furthermore, the restricted number of reports and the lack of uniform clinical assessment of affected individuals did not allow to define more in depth the clinical features and the underlying neural correlates of these uncommon clinical disorders. Here we report an 89-years old woman with a right hemispheric lesion who showed a contralesional defect of eyelid closure. We also include a video neuroimage of this case and a review of eyelid closing and opening disorders in patients with focal unilateral lesions. In this review we found a correlation between right hemisphere and eyelid motor control, particularly for apraxia of eyelid closure affecting only the contralesional eye. The right parietal lobe was most frequently affected in this unilateral form of eyelid closing disorders, whereas putamen and other subcortical structures were more involved in eyelid opening than in eyelid closing disorders. The relations between unilateral eyelid closing disorders and other forms of motor-intentional defects are shortly discussed.

This paper examines the effects of accounting-based thresholds in regulation on growth decisions in the banking industry. To investigate this relation we study changes in growth around the $10 billion asset threshold specified in the Dodd-Frank Act. We first document that, in the years after the new threshold-based regulations are announced, banks slow their asset growth as they approach the threshold and then accelerate their asset growth as they cross the threshold. Next, we document the primary mechanism banks use to achieve each of these changes in growth: reduced deposit growth rates to slow growth and increased acquisition activity to accelerate growth. Finally, we document that, while banks attempt to remain below the threshold, they reduce the growth of their investment portfolio and report a lower return on assets. Also, when banks accelerate growth through acquisition activity, those acquisitions involve larger and riskier target banks. These findings suggest that regulations with accounting-based thresholds can affect growth decisions and profitability in the banking industry.

Background Cranioplasty is both a functional and aesthetical therapeutic option. In the clinical scenario every cranioplasty's material is potentially qualified to achieve the goal of calvarian reconstruction but there is a lack of agreement about the optimum choice, especially between the heterologous ones. The choice of cranioplasty widely depends on surgeon's personal preferences. In this retrospective multicentric study a comparative analysis of hydroxyapatite or titanium cranioplasties was carried on analyzing the main factors considered by the surgeon to choose a material rather than another one. Our results and data were compared with those reported in the scientific literature and a flow-chart regarding the therapeutic approach in the choice of the most suitable cranioplasty was proposed and discussed. Methods The authors present a multicentric study considering 2 groups of patients who underwent 2 different kinds of cranioplasty: hydroxyapatite and titanium. The outcomes measures included the surgical timing and the maintenance of post-operative subgaleal drain. Results A total of 40 patients that had cranioplasty treatment were evaluated. The surgical technique was analyzed. In patients that underwent titanium cranioplasty we observed a reduction in the operative times and in subgaleal drain maintenance. In relation to the age, comorbidity, and neurological status a score, called most suitable material (MSM), was elaborated and a therapeutic algorithm is proposed. Conclusions This study confirms the known advantages and drawback of titanium and hydroxyapatite prostheses. Thanks to the lessons learned from our experience on this field, we elaborated the MSM score that coupled with the therapeutic flow-chart proposed could address the choice of the MSM for a specific patient.

Objective\ud We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs).\ud \ud Methods\ud In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 tertiary movement disorders centers in Italy. Each subject with FMDs underwent a comprehensive clinical assessment, including screening for different subtypes of functional gait disorders. Multivariate regression models were implemented in order to estimate the adjusted odds ratio (OR; 95% confidence interval) of having FGDs in relation to sociodemographic and clinical characteristics.\ud \ud Results\ud Out of 410 FMDs, 26.6% (n = 109) of patients exhibited FGDs. The most frequent FGDs were slow gait (n = 43, 39.4%), astasia-abasia (n = 26, 23.8%), and knee buckling (n = 24, 22%). They exhibited single FGDs in 51.4% (n = 56) or complex FGDs (more than one type of FGDs) in 48.6% (n = 53) of cases. On multivariate regression analysis, the presence of FGDs was more likely associated with older age (OR 1.03, 95% CI 1.01–1.04), functional visual symptoms (OR 2.19, 95% CI 1.08–4.45), and the diagnosis of somatic symptoms disorder (OR 2.97, 95% CI 1.08–8.17). FGDs were also more likely to undergo physiotherapy (OR 1.81, 95% CI 1.08–3.03).\ud \ud Conclusions\ud People with FMDs may present with different and overlapping types of FGDs, which may occur in older age. The association of FGDs with functional visual symptoms and somatic symptoms disorder opens up to new avenues to the understanding of the neural mechanisms of these disorders.

Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm2, p ​

Background and aims The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. Methods SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) “clinical CAD” (prior revascularization history), (b) “subclinical CAD” (CAC >0), (c) “No CAD” (CAC=0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). Results Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p400, respectively, p, Graphical abstract Image 1

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Introduction Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. Objective To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities. Methods Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted. Results A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors. Conclusions Our data support the evidence of a large overlap between FMD phenotypes.