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Our study aims to define resting energy expenditure (REE) and describe the main nutritional patterns in a single-center cohort of children with Smith-Magenis syndrome (SMS). REE was calculated using indirect calorimetry. Patients' metabolic status was assessed by comparing measured REE (mREE) with predictive REE (pREE). Patients also underwent multidisciplinary evaluation, anthropometric measurements and an assessment of average energy intake, using a 3-day food diary, which was reviewed by a specialized dietitian. Twenty-four patients (13 M) were included, the median age was 9 years (IC 95%, 6–14 years), 84% had 17p11.2 deletion, and 16% had RAI1 variants. REE was not reduced in SMS pediatric patients, and the mREE did not differ from the pREE. In patients with RAI1 variants (16%, n = 3/24), obesity was more prevalent than those with 17p11.2 deletion (100% vs 38%). Lower proteins intake and higher total energy intake were reported in obese and overweight patients, compared to healthy weight children. No significant difference was found between males and females in energy or macronutrient intake. Conclusions: In SMS, the onset of obesity is not explained by REE abnormalities, but dietary factors seem to be crucial. Greater concern should be addressed to patients with RAI1 variants. A better understanding of the molecular mechanisms causing obesity in SMS patients could set the basis for possible future targeted therapies. What is Known: • More than 90% of SMS patients after the age of 10 are overweight or obese. What is New: • Onset of overweight and obesity in SMS pediatric patients is not explained by abnormal resting energy expenditure. • The development of syndrome-specific dietary guidelines for SMS patients should be of utmost relevance and are highly needed. [ABSTRACT FROM AUTHOR]

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5–95% CI:1.13–7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis. [ABSTRACT FROM AUTHOR]

The present work offers a comprehensive overview of methods related to condition assessment of bridges through Structural Health Monitoring (SHM) procedures, with a particular interest on aspects of seismic assessment. Established techniques pertaining to different levels of the SHM hierarchy, reflecting increasing detail and complexity, are first outlined. A significant portion of this review work is then devoted to the overview of computational intelligence schemes across various aspects of bridge condition assessment, including sensor placement and health tracking. The paper concludes with illustrative examples of two long-span suspension bridges, in which several instrumentation aspects and assessments of seismic response issues are discussed. [ABSTRACT FROM AUTHOR]

The Shelterin complex protein TPP1 interacts with human telomerase (TERT) by means of the TEL-patch region, controlling telomere homeostasis. Aberrations in the TPP1-TERT heterodimer formation might lead to short telomeres and severe diseases like dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. In the present study, we provide a thorough characterization of the structural properties of the TPP1's OB-domain by combining data coming from microsecond-long molecular dynamics calculations, time-series analyses, and graph-based networks. Our results show that the TEL-patch conformational freedom is influenced by a network of long-range amino acid communications that together determine the proper TPP1-TERT binding. Furthermore, we reveal that in TPP1 pathological variants Glu169Δ, Lys170Δ and Leu95Gln, the TEL-patch plasticity is reduced, affecting the correct binding to TERT and, in turn, telomere processivity, which eventually leads to accelerated aging of affected cells. Our study provides a structural basis for the design of TPP1-targeting ligands with therapeutic potential against cancer and telomeropathies. The binding interaction between the Shelterin complex protein TPP1 and the human telomerase enzyme can trigger telomerase maintenance, however, the conformational change of TPP1 functional for binding remains underexplored. Here, the authors characterize the structural properties of a group of amino acids named the TEL-patch within TPP1's oligosaccharide/oligonucleotide-domain by molecular dynamics simulation, time-series analyses, and graph-based networks, revealing their conformational plasticity and allosteric communication networks. [ABSTRACT FROM AUTHOR]

Cardiac involvement from amyloidosis is of growing interest in the overall literature. Despite cardiac amyloidosis (CA) has been considered for a long time a rare disease, the diagnostic awareness is increasing mainly thanks to the improvement of diagnostic softwares and of imaging techniques such as cardiac magnetic resonance (CMR). Some authors have observed an increase of prevalence rate of CA; moreover it's often underestimated because clinical manifestations are aspecific. The interstitial infiltration of the left ventricle has been extensively studied, while the involvement of the right ventricle (RV) has been less investigated. Involvement of the RV, even in the absence of pulmonary hypertension or clearly left ventricle infiltration, plays an important role as prognostic factor and is useful to achieve an early diagnosis. Therefore, the use of fast and low-cost diagnostic methods such as ultrasound strain of the right ventricle could be used to recognize cardiac amyloidosis early. Herein the importance of evaluating the right ventricular involvement, which can predict the most severe course of the disease also without overt clinical manifestations. The role of imaging, in particular of echocardiography, CMR, and scintigraphy is here reported. [ABSTRACT FROM AUTHOR]

To date, the feeding and oral-motor abilities of patients with CHARGE syndrome (CS) have not been longitudinally assessed. This study aims to investigate the level of these abilities at different ages and evaluate how they evolve during growth. We retrospectively analysed oral-motor features of 16 patients with molecularly confirmed CS (age range 4–21 years old; mean 11 years; SD 6 years; median 10 years). Nearly 100% of CS new-borns had weak sucking at birth, and half of them demonstrated poor coordination between breathing and swallowing. Over time, the percentages of children with tube feeding dependence (60% at birth) faced a slow but steady decrease (from 33% at 6 months, 25% at 12 months, to 13% at school age) in tandem with the decreasing risk of aspiration. The ability of eating foods requiring chewing was achieved at school age, after the acquisition of an adequate oral sensory processing. A mature chewing pattern with a variety of food textures was not achieved by more than half of patients, including those requiring artificial enteral nutrition. Most patients started prolonged oral-motor treatments with speech language therapists in early childhood. Conclusions: Although feeding and swallowing disorders are constant features in CS patients, a slow and gradual development of feeding abilities occurs in most cases. Rehabilitation plays a key role in overcoming structural and functional difficulties and attaining appropriate eating skills. What is Known: • Feeding problems and swallowing dysfunction have been noted in CHARGE syndrome. • The involvement of multiple factors, including structural problems in the mouth, throat, or esophagus, and neurological impairment, make feeding a complicated task in CHARGE individuals. What is New: • Dysphagia gradually improves in most CHARGE children over time, though with a wide interindividual variability. • The percentages of children with tube feeding dependence decrease over time from 60% at birth to 33% at 6 months and 13% at school age. [ABSTRACT FROM AUTHOR]

Predicting structural and energetic properties of a molecular system is one of the fundamental tasks in molecular simulations, and it has applications in chemistry, biology, and medicine. In the past decade, the advent of machine learning algorithms had an impact on molecular simulations for various tasks, including property prediction of atomistic systems. In this paper, we propose a novel methodology for transferring knowledge obtained from simple molecular systems to a more complex one, endowed with a significantly larger number of atoms and degrees of freedom. In particular, we focus on the classification of high and low free-energy conformations. Our approach relies on utilizing (i) a novel hypergraph representation of molecules, encoding all relevant information for characterizing multi-atom interactions for a given conformation, and (ii) novel message passing and pooling layers for processing and making free-energy predictions on such hypergraph-structured data. Despite the complexity of the problem, our results show a remarkable Area Under the Curve of 0.92 for transfer learning from tri-alanine to the deca-alanine system. Moreover, we show that the same transfer learning approach can also be used in an unsupervised way to group chemically related secondary structures of deca-alanine in clusters having similar free-energy values. Our study represents a proof of concept that reliable transfer learning models for molecular systems can be designed, paving the way to unexplored routes in prediction of structural and energetic properties of biologically relevant systems. Machine learning algorithms are widely employed for molecular simulations, but there are likely many yet unexplored routes for the prediction of structural and energetic properties of biologically relevant systems. Here, the authors develop a hypergraph representation and message passing method for transferring knowledge obtained from simple molecular systems onto more complex ones, demonstrated by transfer learning from tri-alanine to the deca-alanine system. [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients' risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs. [ABSTRACT FROM AUTHOR]

Introduction: Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry. Methods: At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM. Results: 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV–V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels. Conclusions: Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF. [ABSTRACT FROM AUTHOR]

In the aftermath of a seismic event, decision-makers have to decide quickly among alternative management actions with limited knowledge on the actual health condition of buildings. Each choice entails different direct and indirect consequences. For example, if a building sustains low damage in the mainshock but people are not evacuated, casualties may occur if aftershocks lead the structure to fail. On the other hand, the evacuation of a structurally sound building could lead to unnecessary financial losses due to business and occupancy interruption. A monitoring system can provide information about the condition of the building after an earthquake that can support the choice between several competing alternatives, targeting the minimization of consequences. This paper proposes a framework for quantifying the benefit of installing a permanent seismic structural health monitoring (S2HM) system to support building evacuation operations after a seismic event. Decision-makers can use this procedure to preventively evaluate the benefit of an SHM system and decide about the worthiness of its installation. [ABSTRACT FROM AUTHOR]

Genomic variant interpretation is a critical step of the diagnostic procedure, often supported by the application of tools that may predict the damaging impact of each variant or provide a guidelines-based classification. We propose the application of Machine Learning methodologies, in particular Penalized Logistic Regression, to support variant classification and prioritization. Our approach combines ACMG/AMP guidelines for germline variant interpretation as well as variant annotation features and provides a probabilistic score of pathogenicity, thus supporting the prioritization and classification of variants that would be interpreted as uncertain by the ACMG/AMP guidelines. We compared different approaches in terms of variant prioritization and classification on different datasets, showing that our data-driven approach is able to solve more variant of uncertain significance (VUS) cases in comparison with guidelines-based approaches and in silico prediction tools. [ABSTRACT FROM AUTHOR]

Purpose of Review: Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas. Recent Findings: Invasive strategies have been recently incorporated in recommendations for the diagnosis and treatment of HCM on both sides of the Atlantic. These guidelines are based on a bulk of well-designed but retrospective studies as well as on expert opinions. Evidence now exists that adequate evaluation and management of HCM requires a multidisciplinary team capable of choosing the best available options. Summary: Management of LVOTO still varies largely based on local expertise and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, the concept of a "HCM heart team" is coming of age. [ABSTRACT FROM AUTHOR]

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4 years, range 16–96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2 min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S′) and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV—right atrial pressure gradient [RV–RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function. [ABSTRACT FROM AUTHOR]

In the last thirty years, Seismic Structural Health Monitoring (S SP 2 sp HM) has received a growing interest from both researchers and professionals, and an increasingly high number of seismic monitoring systems are currently installed in various countries. Therefore, the paper B Liao et al. b shows that medium-quality accelerometers (MEMS-based instruments) can provide feasible solutions for cost-effective city-scale deployment and performances that are superior to those of sensor networks with high-quality accelerometers. Vibration-based damage identification techniques are thus an important decision support tool that is being investigated by several research groups using both data-driven and model-based approaches. [Extracted from the article]

Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case–control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19. [ABSTRACT FROM AUTHOR]

Physical activity is associated with a lower risk of adverse cardiovascular outcomes, including heart failure (HF). Exercise training is a class IA level recommendation in patients with stable HF, but its impact is less clear in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to analyze the effects of the exercise training on cardiovascular outcomes in patients with HFpEF. A systematic literature search was conducted on the main electronic databases, proceedings of major meetings, and reference lists of the identified studies, using specific terms for only English language studies published between 2000 and 2018. We followed the PRISMA to perform our review. Quality of studies was also assessed. The systematic review identified 9 studies on 348 patients, of moderate (n = 2) to good (n = 7) quality. The training consisted of a combination of supervised in-hospital and home-based outpatient programs, including aerobic exercise, endurance and resistance training, walking, and treadmill and bicycle ergometer. Most of the protocols ranged 12–16 weeks, with a frequency of 2–3 sessions weekly, lasting 20–60 min per session. There were significant improvements in peak oxygen uptake, 6-min walking test distance, and ventilatory threshold, whereas quality of life and echocardiographic parameters improved only in some studies. Endothelial function/arterial stiffness remained unchanged. No adverse events were reported. Appropriate exercise programs are able to get a favorable cardiovascular outcome in patients with HFpEF. This could also benefit in terms of quality of life, even if more controversial. Further researches are necessary. [ABSTRACT FROM AUTHOR]

The detailed understanding of the binding of small molecules to proteins is the key for the development of novel drugs or to increase the acceptance of substrates by enzymes. Nowadays, computer-aided design of protein–ligand binding is an important tool to accomplish this task. Current approaches typically rely on high-throughput docking essays or computationally expensive atomistic molecular dynamics simulations. Here, we present an approach to use the recently re-parametrized coarse-grained Martini model to perform unbiased millisecond sampling of protein–ligand interactions of small drug-like molecules. Remarkably, we achieve high accuracy without the need of any a priori knowledge of binding pockets or pathways. Our approach is applied to a range of systems from the well-characterized T4 lysozyme over members of the GPCR family and nuclear receptors to a variety of enzymes. The presented results open the way to high-throughput screening of ligand libraries or protein mutations using the coarse-grained Martini model. Computer-aided design of protein-ligand binding is important for the development of novel drugs. Here authors present an approach to use the recently re-parametrized coarse-grained Martini model to perform unbiased millisecond sampling of protein-ligand binding interactions of small drug-like molecules. [ABSTRACT FROM AUTHOR]

It is generally accepted that climate change is leading to increased frequency of extreme weather events worldwide, and this is placing heavier demands on an already aging infrastructure-network. Bridges are particularly vulnerable infrastructure assets that are prone to damage or failure from climate-related actions. In particular, bridges over waterways can be adversely affected by flooding, specifically the washing away of foundation soils, a mechanism known as scour erosion. Scour is the leading cause of failure for bridges with foundations in water as it can rapidly compromise foundation stiffness often resulting in unacceptable movements or even collapse. There is growing interest among asset managers in applying health monitoring approaches to assess the real-time performance of bridges under damaging actions, including scour. Sensor-based approaches involve the acquisition of data such as dynamic measurements, which can be used to infer the existence of scour or other damage without the laborious requirements of undertaking visual inspections. In this paper, a framework is proposed to assess the benefit obtained from health monitoring systems as compared to the scenario where no monitoring system is employed on a bridge, to ascertain how useful these systems are at assisting decision-making. Decisions typically relate to the implementation of traffic restrictions or even partial or complete bridge closure in the event of damage being detected, which has associated consequences for a network. A case study is presented to demonstrate the approach postulated in this paper. [ABSTRACT FROM AUTHOR]

The management of patients with early stage (cT1-T2) tongue squamous cell carcinoma without clinicoradiologic evidence of neck node metastasis (cN0) has been widely debated over the last 3 decades and still remains controversial. Nevertheless, the identification of patients with low-stage tumours at high-risk for occult cervical metastases is imperative before planning treatments of primary tumours, as well as that of prognostic markers which may possibly select those patients who may benefit of additional workup after surgery in view of the high metastatic potential of the primary tumour. The pre-surgical evaluation of tongue malignant primary tumour (for assessing lateral and deep margins) along with diode laser surgery (with accurate incision, bleeding-free and with reduced/absent post-surgical complications) may lead to a more conservative but equally decisive surgical treatment, also with a greater patient compliance. We studied 85 consecutive cases of cT1-T2 N0 tongue squamous cell carcinoma who had been managed by the following diagnostic/therapeutic protocol: pre-operative high definition ultrasound examination for the evaluation of size and depth, followed by three-dimensional surgical excision by diode laser (wavelength of 800 ± 10 nm, output power of 8 W in continuous wave, flexible optic fibre of 320 μm in contact mode) and detailed histological analyses of well-established prognostic parameters (tumour grade, thickness, depth, front of infiltration and surgical margins) with statistical analysis. No post-surgical photobiomodulation was performed. Overall, 58.82% of patients were stage I, 18% stage II, and the most frequent histotype was squamous cell carcinoma (97.64%). Large nests invasion pattern was observed in 64 cases, expansive pattern in 9, invasion in single cells in 12; front of invasion involved the muscle in 62 cases, vessels in 6, nerves in 15; peritumoural vascular invasion was assessed in 6 patients and perineural invasion in 15. Selective neck lymphadenectomy was performed in 9 cases, and clinically occult node metastases were detected in two cases. At follow-up, 78 patients (98.73%) were alive and free of disease, one patient experienced tumour-related death, while the remaining 6 died for non-disease-related causes. All the histological prognostic parameters were statistically significant (χ2 test; p = 0.05), thus leading to a prognostic weight classification with a three-tiered stratification. On the bases of these results, the authors maintain that the reported diagnostic/therapeutic protocol, including the pre-operative echo-guided three-dimensional evaluation, the following diode laser mini-invasive surgery for tumour excision and the histological examination along with the proposed three-tiered stratification of histological prognostic parameters may allow proper management of clinical stage I and II early tongue carcinomas. [ABSTRACT FROM AUTHOR]

Vibration-based methods for damage localizations often rely on a damage feature defined in terms of changes of modal shapes and localize damage by detecting shape irregularities that are ascribed to local loss of stiffness. In this paper, the performance of several algorithms for damage localization is investigated and the results are compared in terms of the gain of information they provide, which is measured by the relative information entropy also known as Kullback–Leibner (KL) divergence. This parameter is a measure of the difference between two probability distributions and can quantify the information gain achieved using different statistical models. In this paper the relative entropy is used to compare the gain of information obtained using different damage-sensitive indicators retrieved from simulated structural health monitoring data. The investigation is carried out using structural responses simulated using the finite element model of a real bridge permanently monitored by the Italian Seismic Observatory of Structures. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the possibility to extend the storage of unused organ-cultured donor corneas. After 28 days of corneal culture in TISSUE-C (AL.CHI.MI.A. S.R.L., Italy) and 5-day storage in transport/deswelling medium CARRY-C (AL.CHI.MI.A. S.R.L., Italy), 25 corneas that were deemed suitable for transplantation were transferred in fresh TISSUE-C at 31 °C for additional 7 days and then in fresh CARRY-C at room temperature for 24 h. Tissues were assessed for endothelial cell density (ECD), endothelial mortality and morphology after the standard and the extended corneal storage. In addition, the effect of donor age < 85 years and ≥ 85 years on corneal characteristics was assessed. After the extended storage, 6 out of 25 tested corneas (24%) showed ECD values below the acceptance limit (< 2000 cells/mm2). 19 corneas (76%) were still suitable for transplantation and showed a 5.9% loss in ECD, which was not statistically significant (P = 0.0949) compared to standard storage period. The two donor age groups did not show statistically significant differences in any tested parameter, although a trend for lower ECD and higher mortality in Descemet's folds after standard storage was observed in the ≥ 85 age donor group. Thus, the attempt of the current study to provide new sight-restorative options for unused tissues and increasing the availability of corneas in case of shortage gave encouraging results. Although a higher vulnerability of corneas from very old donors could not be statistically demonstrated in the present study, higher sample size could be required for prolonging the shelf life of these tissues. [ABSTRACT FROM AUTHOR]

Despite the widespread availability of several effective classes of drugs, systemic arterial hypertension remains poorly controlled in the majority of patients worldwide. In this article, we discuss the different modalities and effects of combination therapy and possible future research questions. Treatment with a single antihypertensive agent can effectively reduce blood pressure in only a limited number of patients, while most require therapy with two or more agents to achieve target levels. As initial therapy, American and European guidelines suggest a combination of two antihypertensive drugs and the use of a third antihypertensive drug when hypertension is still uncontrolled. Initial combination therapy is recommended in high-risk patients for an immediate blood pressure response, improved tolerability and possibly increased patient adherence. In addition to the potential benefits of combining different drug classes with synergistic pharmacological and physiological actions, this approach is useful for increasing the patient compliance with treatment, in particular if provided at fixed doses in a single pill. The minimisation of side effects is critical for the long-term treatment of a largely asymptomatic condition such as systemic hypertension. Low-dose combinations of different drugs from classes with complementary actions may provide the best ratio of lower side effects and improved tolerability with a significant blood pressure reduction, particularly in high-risk patients. This approach could be aided by a multidisciplinary lifestyle intervention on risk factors. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions. [ABSTRACT FROM AUTHOR]

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF. [ABSTRACT FROM AUTHOR]

Purpose: This is a retrospective analysis including all of the patients that have undergone anterior resection for rectal cancer from January 1998 to December 2005 in two tertiary referral centers. The study aims to evaluate the long term functional results after low anterior resection and to identify the risk factors of postoperative bowel disorders. Method: Data were collected from the clinical records, and then the low anterior resection syndrome score which is a specific questionnaire to investigate the symptoms after surgery was submitted to the selected patients. Exclusion criteria were intra-abdominal rectal cancer, partial mesorectal excision, permanent stoma, recurrent local disease, and patients who declined the questionnaire. Results: A total of 93 patients were included in the analysis with a median age at the diagnosis of 66 years. The median follow-up was 13.7 years, and low anterior resection syndrome was reported in 44 patients (47.5 %), with major manifestations in 19 patients (20.5 %), and minor symptoms in 25 patients (27 %). Age more than 70 years, tumor distance from the external anal verge, neoadjuvant treatment, and interval time of closing stoma are independent prognostic factors of functional disorders after surgery. Conclusions: Because of its great impact on the quality of life of these patients, it is necessary to early identify the syndrome trying to reduce its manifestations. Moreover, the symptoms seem to remain stable 1 year after surgery; hence, it is important to have an exhaustive, preoperative counseling and an integrated post-operative functional and rehabilitational follow-up in association with the oncologic pathway. [ABSTRACT FROM AUTHOR]

This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units (Mid-South of Italy), and in 100 healthy Caucasian subjects randomly recruited from the same area. Cardiac anatomy and function were analysed by non invasive diagnostic imaging techniques (Echocardiography standard m-mode, 2D, colour-Doppler) and by invasive studies (cardiac catheterization). Molecular screening of the region of interest was performed by automated sequencing. At univariate analysis, patients with the His323His TT genotype show a lower cardiac index (2 ± 0.6 vs. 2.3 ± 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 ± 9.6 vs. 14.2 ± 6.9; p = 0.01) at cardiac catheterization. A logistic multivariate model shows idiopathic disease (p = 0.01; OR = 3.8; CI = 1.3-11) and indexed pulmonary vascular resistances (p = 0.01; OR = 1.1; CI = 1-1.2) as independent predictors of TT genotype. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 μM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis. [ABSTRACT FROM AUTHOR]

In this paper two methods for damage localization, the IDDM (Interpolation Damage Detecting Method), and the Modal Shape Curvature Method (MSCM) are applied to the same experimental case of a cantilever aluminum beam for which several different damage scenarios have been artificially reproduced in laboratory. IDDM is a new method recently proposed in literature which is on the definition of a damage-sensitive feature in terms of the accuracy of a spline function interpolating the Operational Displacement Shapes of the structure. This paper will present a comparison between the two methods on experimental data from a laboratory bench structure. Results show that, due to the small changes of the damage features induced by damage, both methods require a high-quality data set to provide a reliable damage localization even if the number of false alarms is slightly lower if the IDDM is applied. [ABSTRACT FROM AUTHOR]

Background: To date, therapeutic guidelines and pattern of reflux for patients with no-dysplasia (ND) or low-grade dysplasia (LGD) Barrett's esophagus (BE) remain unclear. We aimed to analyze pattern of reflux and regression of ND- or LGD-BE after medical and surgical treatment. Methods: We studied a cohort of ND- and LGD-BE patients who underwent laparoscopic total fundoplication and a cohort of ND- and LGD-BE patients managed medically. Patients were matched for age, sex, and disease duration. After 1 year of follow-up at least, all patients underwent upper endoscopy with esophageal biopsies to evaluate any histological changes, as well as manometry and impedance-pH-metry to re-assess reflux patterns. Results: Thirty-seven patients (20 LGD, 17 ND) undergoing laparoscopic fundoplication were enrolled and compared with 25 patients (13 LGD, 12 ND) managed with proton pump inhibitors (PPI). Laparoscopic fundoplication resulted in a better control of both acidic and weakly acidic reflux ( P < 0.001) and was associated with a higher probability of reversion for LGD ( P < 0.01). Esophageal motility did not differ between surgically and medically treated patients. Conclusions: In patients with ND- or LGD-BE, laparoscopic fundoplication seems to warrant a better control of all kinds of refluxate and it is associated with a higher likelihood of reversion of both LGD- and ND-BE, compared with PPI therapy. [ABSTRACT FROM AUTHOR]

We analyzed by next-generation sequencing (NGS) 67 epilepsy genes in 19 patients with different types of either isolated or syndromic epileptic disorders and in 15 controls to investigate whether a quick and cheap molecular diagnosis could be provided. The average number of nonsynonymous and splice site mutations per subject was similar in the two cohorts indicating that, even with relatively small targeted platforms, finding the disease gene is not an univocal process. Our diagnostic yield was 47% with nine cases in which we identified a very likely causative mutation. In most of them no interpretation would have been possible in absence of detailed phenotype and familial information. Seven out of 19 patients had a phenotype suggesting the involvement of a specific gene. Disease-causing mutations were found in six of these cases. Among the remaining patients, we could find a probably causative mutation only in three. None of the genes affected in the latter cases had been suspected a priori. Our protocol requires 8-10 weeks including the investigation of the parents with a cost per patient comparable to sequencing of 1-2 medium-to-large-sized genes by conventional techniques. The platform we used, although providing much less information than whole-exome or whole-genome sequencing, has the advantage that can also be run on 'benchtop' sequencers combining rapid turnaround times with higher manageability. [ABSTRACT FROM AUTHOR]

To help teachers, recent years have witnessed a proliferation of techniques and systems based on Artificial Intelligence and, in particular, on Machine Learning. The second paper, "Natural Language Generation Using Deep Learning to Support MOOC Learners", by Chenglu Li and Wanli Xing, examines the extent to which the deep-learning-based natural language generation models, can offer responses similar to human-generated responses to the learners in MOOC forums. The published papers address some of the open issues with respect to assessment in science courses, human simulated responses and drop-out prediction, using novel artificial intelligence techniques. [Extracted from the article]