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Background Primary antiphospholipid syndrome (PAPS) is characterized by the presence of antiphospholipid antibodies (aPL), repetitive fetal loss, and arterial/venous thrombosis and no association with other autoimmune rheumatic disease. Ocular involvement can also occur including retinal vascular thrombosis and neuro-ophthalmological manifestations, such as optic neuropathy and amaurosis fugax. Early detection of ocular changes is crucial to minimize functional loss. Purpose To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with PAPS without ocular complaints and compare with healthy individuals. Methods We performed a complete structural and functional ophthalmological evaluation using OCTA and microperimetry exam in patients with PAPS, followed at a tertiary Rheumatology outpatient clinic. Results We included 104 eyes of 52 subjects [PAPS without ocular complaints (N = 26) and healthy individuals (N = 26)]. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. PAPS manifestations were venous (65.4%), arterial thrombosis (34.6%), and obstetrical (34.6%) and all of them had lupus anticoagulant. Ophthalmologic findings were more frequent in PAPS compared to healthy individuals (19.2% vs. 0%, p = 0.05). The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (PPE) (1 patient, 1 eye). Hypertension and hyperlipidemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together ( p = 0.03). Conclusions We provide novel evidence that approximately 20% of our asymptomatic PAPS patients without ocular symptoms have ophthalmologic findings that require early identification and careful surveillance focusing on minimizing systemic and vascular risk factors.

Background The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded on October 1, 2018, to enhance cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic arteriopathy has been selected as the very first topic to be investigated by the federation. Methods MeFAVS members were asked to reply to a questionnaire on the management of diabetic ischemic foot. Results were collected and analyzed statistically. The questionnaire consisted of 15 multiple choice answers regarding diabetic foot (DF) diagnosis and treatment. The questionnaire was submitted to 21 centers on April 20, 2019. Results Response rate was 62%. The survey revealed that vascular surgeons, diabetologists, and wound care nurses made-up the core of the diabetic teams present in 76.9%, 69.3%, and 92.3% of the centers, respectively. Diabetic teams were most often led by vascular surgeons (53.8%) and diabetologists (42.2%), but only in 7.9% of cases by nurses. Duplex ultrasonography and computed tomographic angiography were the most commonly available tools used to assess diabetic peripheral arterial disease (PAD). Surgical wound care was undertaken by vascular surgeons in the majority of cases, and only in 46.2% of the cases to orthopedic or plastic surgeons, while nonsurgical wound care was handled by specialized nurses (76.6%) and diabetologists (53.8%). First-line revascularization was preferred over conservative treatment (61.5% vs 53.8%) and endovascular strategy (45.3%) over open (33.7%) or hybrid (21.0%) surgery. Vascular surgeons and interventional radiologists were found to be the most common performers of endovascular revascularization (92.3% and 53.8%, respectively). Amputations had an overall rate of 16.6% (range 4–30%) and a mean reintervention rate of 22.5%, and were usually performed by vascular surgeons for both minor and major interventions (84.6%) followed by orthopedic surgeons (15.4% minor and 30.8% major). The availability of a DF clinic (84.6%) and endovascular (53.8%) and open surgery (46.2%) capabilities were considered fundamental to reduce amputation rates. Conclusions Especially since the introduction and spreading of new endovascular techniques for the treatment of DF, it is a common consensus amongst vascular surgeons that a standardized approach to the discipline is necessary in order to improve outcomes such as amputation-free survival and mortality and it is with this perspective and purpose that transnational cooperation amongst vascular professionals and residents in training are aiming for greater proficiency in endovascular and open surgery.

Background Substance Use Disorder (SUD) causes a great deal of personal suffering for patients. Recent evidence highlights how defenses and emotion regulation may play a crucial part in the onset and development of this disorder. The aim of this study was to investigate potential differences in the defensive functioning between SUD patients and non-clinical controls. Secondly, we aimed at investigating the relationships between alexithymia and maladaptive/assimilation defenses. Methods The authors assessed defensive functioning (Response Evaluation Measure-71, REM-71), personality (MMPI-II), and alexithymia (TAS-20) of 171 SUD patients (17% female; mean age = 36.5), compared to 155 controls. Authors performed a series of ANOVAs to investigate the defensive array in SUD patients compared to that of non-clinical controls. Student t test for indipendent samples was used to compare clinical characteristics between the SUD group and the controls. To investigate the role of single defenses in explaining alexithimia’s subscores, stepwise multiple regression analysis were carried out on socio-demographic characteristics of participants (gender, age, and years of education), with REM-71 defenses as predictors. Results SUD patients presented a more maladaptive/assimilation (Factor 1) defensive array (p Projection (38% of variance explained, β = .270, p Conclusion The REM-71 and the TAS-20 might be useful screening instruments among SUD patients.

Objective To analyze whether maternal age at first pregnancy and parity are mediators of the association between early menarche and metabolic syndrome in a sample of middle-aged and older women. Methods Cross-sectional study of 428 women (40 to 80 y), who had experienced a pregnancy in their lifetime, was performed between 2014 and 2016. Age at first pregnancy, parity, and early menarche were self-reported. Metabolic syndrome was assessed using the criteria described by the National Cholesterol Education Program's Adult Treatment Panel III. The association between metabolic syndrome and early menarche was assessed by logistic regression analysis. The mediating role of age at first pregnancy and multiparity in the relationship between early menarche and metabolic syndrome was assessed through mediation analysis, adjusted for covariates. Results According to adjusted logistic regression models, early menarche was associated with higher odds of prevalent metabolic syndrome (OR: 2.26; 95% CI: 1.15-4.46). Mediation analysis showed a significant direct effect of early menarche on metabolic syndrome (β: 0.808; 95% CI: 0.107-1.508). Of the two mediators tested, age at first pregnancy was significant (β: 0.065; 95% CI: 0.004-0.221), ie, participants with and without early menarche differ, on average, by 0.879 SDs in the log odds of MetS (total effect), of which 0.065 SDs (8%), on average, would be attributable to the effect of early menarche on age at first pregnancy (indirect effect), which, in turn, affects MetS. Conclusions Age at first pregnancy may partially contribute to the association between early menarche and metabolic syndrome among middle-aged and older women who had experienced a pregnancy over their lifetime.

Electrochemical detection based on cyclodextrin supramolecular complexes is founded on the competitive binding between electroactive probes and target molecules. This limits their versatility to be used for sensing a broad range of metabolites. In this work, we demonstrate the significant role of zinc ions as well as of beta-cyclodextrins modified with dipicolylamine and of a phenylboronic acid-modified ferrocene probe to address a selective electrochemical detection of adenosin triphosphate (ATP). Our findings will definitively have an impact in oncological point-of-care systems, since a high level of extracellular ATP reveals the inflammatory response due to chemotherapeutic treatments.

Bone marrow mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative potential. However, culture conditions govern their metabolic processes and therapeutic efficacy. Here we show that culturing donor-derived MSCs in Plasmax™, a physiological medium with the concentrations of nutrients found in human plasma, supports their proliferation and stemness, and prevents the nutritional stress induced by the conventional medium DMEM. The quantification of the exchange rates of metabolites between cells and medium, untargeted metabolomics, stable isotope tracing and transcriptomic analysis, performed at physiologically relevant oxygen concentrations (1%O2), reveal that MSCs rely on a high rate of glucose to lactate conversion, coupled with parallel anaplerotic fluxes from glutamine and glutamate to support citrate synthesis and secretion. These distinctive traits of MSCs shape the metabolic microenvironment of the bone marrow niche and can influence nutrient cross-talks under physiological and pathological conditions.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.

Background Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF1) is a well-known mitochondrial protein. Recently, it has been discovered in the human serum where it is reported to be involved in the HDL-cholesterol intake. Here we report the IF1 presence in the serum of two paediatric SLOS dizygotic twins treated with dietary cholesterol supplementation. Case presentation The patients showed a typical phenotype. They started dietary supplementation with cholesterol when 2 months old. The cholesterol intake was periodically titrated on the basis of weight increase and the twin 1 required a larger supplementation than the twin 2 during the follow-up. When 6.4-year-old, they underwent IF1 assay that was 7-fold increased in twin 2 compared to twin 1 (93.0 pg/ml vs 13.0 pg/ml, respectively). Conclusions We report, for the first time, the presence of circulating IF1 in the serum of SLOS patients, showing different levels among them. Our findings confirm that IF1 could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF1 as a new modulator of cholesterol levels.

The objective of these Guidelines was to revise and update the previous 2016 Italian Guidelines on Abdominal Aortic Aneurysm Disease, in accordance with the National Guidelines System (SNLG), to guide every practitioner toward the most correct management pathway for this pathology. The methodology applied in this update was the GRADE-SIGN version methodology, following the instructions of the AGREE quality of reporting checklist as well. The first methodological step was the formulation of clinical questions structured according to the PICO (Population, Intervention, Comparison, Outcome) model according to which the Recommendations were issued. Then, systematic reviews of the Literature were carried out for each PICO question or for homogeneous groups of questions, followed by the selection of the articles and the assessment of the methodological quality for each of them using qualitative checklists. Finally, a Considered Judgment form was filled in for each clinical question, in which the features of the evidence as a whole are assessed to establish the transition from the level of evidence to the direction and strength of the recommendations. These guidelines outline the correct management of patients with abdominal aortic aneurysm in terms of screening and surveillance. Medical management and indication for surgery are discussed, as well as preoperative assessment regarding patients' background and surgical risk evaluation. Once the indication for surgery has been established, the options for traditional open and endovascular surgery are described and compared, focusing specifically on patients with ruptured abdominal aortic aneurysms as well. Finally, indications for early and late postoperative follow-up are explained. The most recent evidence in the Literature has been able to confirm and possibly modify the previous recommendations updating them, likewise to propose new recommendations on prospectively relevant topics.

Background Psycho-oncology literature pointed out that individual health outcomes may depend on patients’ propensity to adopt approach or, conversely, avoidant coping strategies. Nevertheless, coping factors associated with postoperative distress remain unclear, unfolding the lack of tailored procedures to help breast cancer patients manage the psychological burden of scheduled surgery. In view of this, the present study aimed at investigating: 1. pre-/post-surgery distress variations occurring among women diagnosed with breast cancer; 2. the predictivity of approach and avoidant coping strategies and factors in affecting post-surgery perceived distress. Methods N = 150 patients (mean age = 59.37; SD = ± 13.23) scheduled for breast cancer surgery were administered a screening protocol consisting of the Distress Thermometer (DT) and the Brief-COPE. The DT was used to monitor patients’ distress levels before and after surgery (± 7 days), whereas the Brief-COPE was adopted only preoperatively to evaluate patients’ coping responses to the forthcoming surgical intervention. Non-parametric tests allowed for the detection of pre-/post-surgery variations in patients’ perceived distress. Factor analysis involved the extraction and rotation of principal components derived from the Brief-COPE strategies. The predictivity of such coping factors was investigated through multiple regression (Backward Elimination). Results The Wilcoxon Signed-Rank Test yielded a significant variation in DT mean scores (TW = -5,68 cognitive processing (i.e., planning + acceptance + active coping + positive reframing); 2. support provision (i.e., instrumental + emotional support); 3. emotion-oriented detachment (i.e., self-blame + behavioral disengagement + humor + denial); 4. goal-oriented detachment (i.e., self-distraction). Among these factors, support provision (B = .458; β = − .174; t = − 2.03; p = .045), encompassing two approach coping strategies, and goal-oriented detachment (B = .446; β = − .176; t = − 2.06; p = .042), consisting of one avoidant strategy, were strongly related to post-surgery distress reduction. Conclusion The present investigation revealed that the pre-surgery adoption of supportive and goal-oriented strategies led to postoperative distress reduction among breast cancer patients. These findings highlight the importance of timely psychosocial screening and proactive interventions in order to improve patients’ recovery and prognosis.

Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to l-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to l-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid trade-off. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to l-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P < .05), secrete more asparagine (P < .05), and protect leukemic blasts (P

Cytokine release syndrome (CRS) represents a life‐threatening side effect after haploidentical stem cell transplantation (Haplo‐SCT) with posttransplant cyclophosphamide (PT‐Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo‐SCT with PT‐Cy. The two cohorts were similar in main patients’ characteristics besides disease type (P = .02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High‐grade fever (39°‐41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P = .0005; 87% vs 71%, P = .009; 20% vs 7%, P = .07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1‐year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P = .002) and 40% vs 8% (P = .005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P = .002), HLA‐DRB1 mismatching (57% vs 14%, P = .007), and PBSC graft (P = .07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P = .005) and HLA‐DRB1 mismatching (HR: 17.19, P = .003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo‐SCT with PT‐Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA‐DRB1 mismatching., Severe cytokine release syndrome (CRS) may occur after T‐cell‐replete haploidentical stem cell transplantation and conditions nonrelapse mortality. Disease burden and HLA mismatch in the graft‐vs‐host‐disease direction are the main factors affecting the occurrence of severe CRS.

This study reports on the fabrication and characterization of an event detection subsystem composed of a flexible piezoelectric pressure sensor and the electronic interface to be integrated into an implantable artificial pancreas (IAP) for diabetic patients. The developed sensor is made of an AlN layer, sandwiched between two Ti electrodes, sputtered on Kapton substrate, with a preferential orientation along c-axis which guarantees the best piezoelectric response. The IAP is made of an intestinal wall-interfaced refilling module, able to dock an ingestible insulin capsule. A linearly actuated needle punches the duodenum tissue and then the PDMS capsule to transfer the insulin to an implanted reservoir. The device is located at the connection of the needle with the linear actuator to reliably detect the occurred punching of the insulin-filled capsule. Finite Element Analysis (FEA) simulations were performed to evaluate the piezoelectric charge generated for increasing loads in the range of interest, applied on both the sensor full-area and footprint area of the Hamilton needle used for the capsule punching. The sensor-interface circuit was simulated to estimate the output voltage that can be obtained in real operating conditions. The characterization results confirmed a high device sensitivity during the punching, in the low forces (0–4 N) and low actuator speed (2–3 mm/s) ranges of interest, meeting the requirement of the research objective. The choice of a piezoelectric pressure sensor is particularly strategic in the medical field due to the request of self-powered implantable devices which do not need any external power source to output a signal and harvest energy from natural sources around the patient.

Monocytes are a heterogeneous cell population distinguished into three subsets with distinctive phenotypic and functional properties: “classical” (CD14++CD16-), “intermediate” (CD14++CD16+), and “nonclassical” (CD14+CD16++). Monocyte subsets play a pivotal role in many inflammatory systemic diseases including atherosclerosis (ATS). Only a low number of studies evaluated monocyte behavior in patients affected by cardiovascular diseases, and data about their role in acute aortic dissection (AAD) are lacking. Thus, the aim of this study was to investigate CD14++CD16-, CD14++CD16+, and CD14+CD16++ cells in patients with Stanford-A AAD and in patients with carotid artery stenosis (CAS).Methods. 20 patients with carotid artery stenosis (CAS group), 17 patients with Stanford-A AAD (AAD group), and 17 subjects with traditional cardiovascular risk factors (RF group) were enrolled. Monocyte subset frequency was determined by flow cytometry.Results. Classical monocytes were significantly increased in the AAD group versus CAS and RF groups, whereas intermediate monocytes were significantly decreased in the AAD group versus CAS and RF groups.Conclusions. Results of this study identify in AAD patients a peculiar monocyte array that can partly explain depletion of T CD4+ lymphocyte subpopulations observed in patients affected by AAD.

The aim of this study is to evaluate the role of preoperative ischemic brain lesion (IBL) volume, assessed by Diffusion-weighted magnetic resonance brain imaging (DW-MRI) with RAPID® processing, and surgery timing in predicting post-operative neurological outcomes in symptomatic carotid stenosis (SCS) patients treated with carotid endarterectomy (CEA).All patients with SCS who underwent CEA between January 2010 and June 2020 were considered. IBLs ipsilateral to the stenosis were identified in the preoperative magnetic resonance brain (MRI). The volume was quantified in mL and correlated with 30-day rates of stroke and stroke/death by χ2 and receiver operating characteristic (ROC) curve.One hundred thirty-four patients were surgically treated for SCS during the entire study period. CEA procedures were defined as emergent, urgent, or elective if performed within 48 hr, between 48 hr and 14 days, or after 14 days from symptoms onset, respectively. Cumulative new ipsilateral stroke rate was 4,5%, with a statistically higher neurological complications in emergent patients compared to urgent and elective patients (10,6%, 1,47% and 0% respectively, P 0,039). ROC curve analysis showed a volume of 10 mL was predictive of postoperative stroke with 100% sensitivity and 80% specificity. An IBL volume10 mL was an independent risk factor for postoperative stroke. In fact, the perioperative neurological complication rate was significantly different in high-IBL volume patients (10 mL) compared with low-IBL volume patients (10 mL) (P 0,003) CONCLUSIONS: The present study suggests that the optimal timing for CEA is between 48 hr and 14 days. Furthermore, the present study suggests that the presence of the IBL, by itself, is not definitively related with an unsatisfactory neurological outcome. However, an IBL higher than 10 mL should be as a reliable threshold value adverse neurological result in SCS patients.

Background Obstructive sleep apnea (OSA) is often associated with clinical, psychological and neuropsychological comorbidities such as Mild Cognitive Impairment (MCI). This study evaluated changes in clinical, psychosocial, Health Related Quality of Life (HRQoL) and neuropsychological profile in OSA subjects after ventilatory therapy, making comparison with normative data. The aim of the study was to verify the suitability of the HRQoL and neuropsychological screening tests in detecting variations in OSA subjects. Methods At baseline, 32 OSA subjects underwent the following assessment: EuroQol (EQ-5D-3L) and EQ VAS, Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). After the ventilatory titration, 31 OSA subjects repeated the EQ VAS, MoCA and FAB assessment. Results The analyzed subjects (77% male, 58.97±10.06 years old and 47.34±26.67 AHI [ev*hr-1]) showed low emotive distress, a lower perception of HRQoL than normative data and 35.48% of them exhibited executive deficits, too. MCI was detected in 3.2% and 48.4% of subjects after normative Italian and international correction, respectively. Subsequently the ventilatory therapy and the rehabilitative interdisciplinary treatment, subjects improved in EQ VAS (68.23±18.73 vs. 87.13±10.80, P=0.0001), FAB scores (15,30±2.03 vs. 16,65±1,40, P=0.007) and MoCA memory subtest scores (2.16±1.34 vs. 3.06±1.63, P=0.008). Conclusions Ventilatory therapy provided during a rehabilitative and interdisciplinary program increased subjects' HRQoL, executive functions and verbal memory.

Objectives: This study sought to evaluate 30-day safety and efficacy of dual-layer mesh-covered carotid stent systems for carotid artery stenting (CAS) in the clinical practice. Background: When compared with carotid endarterectomy, CAS has been associated with a higher rate of post procedural neurologic events; these could be related to plaque's debris prolapsing through stent's mesh. Consequently, the need for increased plaque coverage has resulted in the development of dual-layer mesh-covered carotid stent systems. Methods: From January 2017 to June 2019, a physician-initiated, prospective, multispecialty registry enrolled 733 consecutive patients undergoing CAS using the CGuard embolic prevention system in 20 centers. The primary endpoint was stroke up to 30 days; secondary endpoints were technical and procedural success; external carotid artery occlusion; and in-hospital and 30-day transient ischemic attack (TIA), acute myocardial infarction (AMI), and death rates. Results: Symptoms were present in 131 (17.87%) patients. An embolic protection device was used in 731 (99.72%) patients. Procedural success was 100%, technical success was obtained in all but 1 (99.86%) patient, who died in hospital due to a hemorrhagic stroke. Six TIAs, 2 minor strokes, and 1 AMI occurred during in-hospital stay, and external carotid artery occlusion was evident in 8 (1.09%) patients. Between hospital discharge and 30-day follow-up, 2 TIAs, 1 minor stroke, and 3 AMIs occurred. Therefore, the cumulative stroke rate was 0.54%. Conclusions: This real-world registry suggests that use of CGuard embolic prevention system in clinical practice is safe and associated with a minimal occurrence of adverse neurological events up to 30-day follow-up.

Introduction: Obstructive sleep apnea is characterized by a reduced airflow through the upper airways during sleep. Two forms of obstructive sleep apnea are described: the central form and the obstructive form. The obstructive form is related to many factors, such as the craniofacial morphology. Objective: To evaluate the correlation between the morphology of the cranial base, of the mandible and the maxilla, and obstructive sleep apnea severity. Methods: Eighty-four patients, mean age of 50.4 years old; 73 males and 11 females with obstructive sleep apnea were enrolled in the present study. Patients with high body mass index and comorbidities were excluded. Lateral cephalograms and polysomnography were collected for each patient to evaluate the correlation between craniofacial morphology and obstructive sleep apnea severity. A Spearman’s rho correlation test between cephalometric measurements and obstructive sleep apnea indexes was computed. Statistical significance was set at p < 0.05. Results: Patients with a severe obstructive sleep apnea presented a reduction of sagittal growth of both effective mandibular length and cranio-basal length. The mandibular length was the only variable with a statistical correlation with apnea-hypopnea index. Vertical dimension showed a weak correlation with the severity of obstructive sleep apnea. No correlation with maxillary sagittal dimension was shown. Conclusion: Obstructive sleep apnea severity may be correlated to mandibular and cranial base growth. Facial vertical dimension had no correlation with obstructive sleep apnea severity. Resumo Introdução: A apneia obstrutiva do sono é caracterizada por um fluxo de ar reduzido nas vias aéreas superiores durante o sono. Duas formas de apneia são descritas: a forma central e a forma obstrutiva. A forma obstrutiva tem sido relacionada a vários fatores, como a morfologia craniofacial. Objetivo: Avaliar a correlação entre a morfologia da base do crânio, da mandíbula e da maxila e a gravidade da apneia obstrutiva do sono. Método: Foram incluídos no presente estudo 84 pacientes com apneia obstrutiva do sono, com média de 50,4 anos; 73 homens e 11 mulheres. Pacientes com alto índice de massa corpórea e comorbidades foram excluídos. Foram coletados cefalogramas laterais e polissonografia para cada paciente para avaliar a correlação entre a morfologia craniofacial e a gravidade da apneia. Foi computado o coeficiente de correlação de postos de Spearman (rho) entre medidas cefalométricas e índices de apneia obstrutiva do sono. A significância estatística foi estabelecida em p < 0,05. Resultados: Pacientes com apneia obstrutiva do sono grave apresentaram redução do crescimento sagital do comprimento mandibular efetivo e do comprimento crânio-basal. O comprimento mandibular foi a única variável que apresentou correlação estatística com o índice de apneia-hipopneia. A dimensão vertical mostrou uma fraca correlação com a gravidade da apneia. Não foi demonstrada correlação com a dimensão maxilar sagital. Conclusão: A gravidade da apneia obstrutiva do sono pode estar correlacionada ao crescimento da base mandibular e craniana. A dimensão facial vertical não apresentou correlação com a gravidade da apneia.

The aim of this study was to evaluate the 1-year safety and efficacy of a dual-layered stent (DLS) for carotid artery stenting (CAS) in a multicenter registry.DLS have been proved to be safe and efficient during short-term follow-up. Recent data have raised the concern that the benefit of CAS performed with using a DLS may be hampered by a higher restenosis rate at 1 year.From January 2017 to June 2019, a physician-initiated, prospective, multispecialty registry enrolled 733 consecutive patients undergoing CAS using the CGuard embolic prevention system at 20 centers. The primary endpoint was the occurrence of death and stroke at 1 year. Secondary endpoints were 1-year rates of transient ischemic attack, acute myocardial infarction, internal carotid artery (ICA) restenosis, in-stent thrombosis, and external carotid artery occlusion.At 1 year, follow-up was available in 726 patients (99.04%). Beyond 30 days postprocedure, 1 minor stroke (0.13%), four transient ischemic attacks (0.55%), 2 fatal acute myocardial infarctions (0.27%), and 6 noncardiac deaths (1.10%) occurred. On duplex ultrasound examination, ICA restenosis was found in 6 patients (0.82%): 2 total occlusions and 4 in-stent restenoses. No predictors of target ICA restenosis and/or occlusion could be detected, and dual-antiplatelet therapy duration (90 days vs 30 days) was not found to be related to major adverse cardiovascular event or restenosis occurrence.This real-world registry suggests that DLS use in clinical practice is safe and associated with minimal occurrence of adverse neurologic events up to 12-month follow-up.

Background Patients with acute heart failure (AHF) show high levels of fibroblast growth factor-23 (FGF23) on admission. We examined if plasma FGF23 changes during an episode of AHF, and if FGF23 holds prognostic significance in this setting. Methods Consecutive AHF patients were enrolled. Blood samples were collected on admission and at discharge. Patients were then followed for all-cause death or HF hospitalization. Results Patients (n = 125; median age 76 years [interquartile interval 71–83], 63% men, left ventricular ejection fraction 35% [25%–56%]) had median admission FGF23 70 ng/L (47–100), N-terminal pro-B-type natriuretic peptide (NT-proBNP) 5844 ng/L (2,503-10,468), high-sensitivity troponin T (hs-TnT) 40 ng/L (25–72), and soluble suppression of tumorigenesis-2 (sST2) 26 ng/mL (17–37). While other biomarkers decreased, FGF23 increased by 15% from admission to discharge (p = 0.033), with a significant correlation with percent changes in estimated glomerular filtration rate (rho = 0.306, p = 0.001). Over a 12-month follow-up, 64 patients (51%) experienced the endpoint. They were more often men, older, with higher systolic pulmonary artery pressure (sPAP), higher NT-proBNP, hs-TnT and discharge FGF23. The best FGF23 cut-off at discharge from receiver operating characteristics analysis was 78 ng/L. Both discharge FGF23 and the 78 ng/L cut-off independently predicted outcome in models including gender, sPAP, age, and 1) admission NT-proBNP, 2) discharge NT-proBNP, 3) admission NT-proBNP and hs-TnT, 4) discharge NT-proBNP and hs-TnT. The 78 ng/L cut-off also refined risk reclassification. Conclusions During an AHF episode, FGF23 increases from admission to discharge, and patients with higher discharge FGF23 have a higher risk of worse outcome.

Purpose The main objective of this work is to investigate hemodynamics phenomena occurring in EVAS (Endo Vascular Aneurysm Sealing), to understand if and how they could lead to type 1a endoleaks and following re-intervention. To this aim, methods based on computational fluid mechanics are implemented as a tool for checking the behavior of a specific EVAS configuration, starting from the post-operative conditions. Pressure and velocity fields are detailed and compared, for two configurations of the Nellix, one as attained after correct implantation and the other in pathological conditions, as a consequence of migration or dislocation of endobags. Methods The computational fluid dynamics (CFD) approach is used to simulate the behavior of blood within a segment of the aorta, before and after the abdominal bifurcation. The adopted procedure allows reconstructing the detailed vascular geometry from high-resolution computerized tomography (CT scan) and generating the mesh on which the equations of fluid mechanics are discretized and solved, in order to derive pressure and velocity field during heartbeats. Results The main results are obtained in terms of local velocity fields and wall pressures. Within the endobags, velocities are usually quite regular during the whole cardiac cycle for the post-implanted condition, whereas they are more irregular for the migrated case. The largest differences among the two cases are observed in the shape and location of the recirculation region in the rear part of the aorta and the region between the endobags, with the formation of a gap due to the migration of one or both of the two. In this gap, the pressure fields are highly different among the two conditions, showing pressure peaks and pressure gradients at least four times larger for the migrated case in comparison to the post-implanted condition. Conclusions In this paper, the migration of one or both endobags is supposed to be related to the existing differential pressures acting in the gap formed between the two, which could go on pushing the two branches one away from the other, thus causing aneurysm re-activation and endoleaks. Regions of flow recirculation and low-pressure drops are revealed only in case of endobag migration and in presence of an aneurysm. These regions are supposed to lead to possible plaque formation and atherosclerosis.

BACKGROUND: In actuality, it is difficult to obtain an early prognostic stratification for patients with acute respiratory failure treated with noninvasive ventilation (NIV). We tested whether an early evaluation through a predictive scoring system could identify subjects at risk of in-hospital mortality or NIV failure. METHODS: This was a retrospective study, which included all the subjects with acute respiratory failure who required NIV admitted to an emergency department–high-dependence observation unit between January 2014 and December 2017. The HACOR (heart rate, acidosis [by using pH], consciousness [by using the Glasgow coma scale], oxygenation [by using P aO 2 / F IO 2 ], respiratory rate) score was calculated before the NIV initiation (T0) and after 1 h (T1) and 24 h (T24) of treatment. The primary outcomes were in-hospital mortality and NIV failure, defined as the need for invasive ventilation. RESULTS: The study population included 644 subjects, 463 with hypercapnic respiratory failure and an overall in-hospital mortality of 23%. Thirty-six percent of all the subjects had NIV as the “ceiling” treatment. At all the evaluations, nonsurvivors had a higher mean ± SD HACOR score than did the survivors (T0, 8.2 ± 4.9 vs 6.1 ± 4.0; T1, 6.6 ± 4.8 vs 3.8 ± 3.4; T24, 5.3 ± 4.5 vs 2.0 ± 2.3 [all P 5 (Relative Risk [RR] 2.39, 95% CI 1.60–3.56) was associated with an increased mortality rate, independent of age and the Sequential Organ Failure Assessment score. CONCLUSIONS: Among the subjects treated with NIV for acute respiratory failure, the HACOR score seemed to be a useful tool to identify those at risk of in-hospital mortality.

The number of patients treated with direct oral anticoagulants is increasing worldwide. Although bleeding complications associated with direct oral anticoagulants are lower than those associated with vitamin K antagonists, the increased number of patients treated with these anticoagulants suggests that a higher absolute number of patients are at risk. Tube thoracostomy is an invasive procedure with a high risk of bleeding. To date, among direct oral anticoagulants, only dabigatran has a well-studied antidote to reverse its effects during emergency procedure or surgery. This report describes a case in which emergency placement of a tube thoracostomy, in a patient with type 2 respiratory failure due to left tension pneumothorax and receiving the anticoagulant rivaroxaban, in the pharmacokinetics phase with greater anticoagulant effect, did not result in bleeding greater than that typically encountered during such interventions. The procedure ended successfully with no acute complications.

Close monitoring of vital physiological parameters is often key in following the evolution of certain medical conditions (e.g., diabetes, infections, post-operative status or post-traumatic injury). The allocation of trained medical staff and specialized equipment is, therefore, necessary and often translates into a clinical and economic burden on modern healthcare systems. As a growing field, transient electronics may establish fully bioresorbable medical devices capable of remote real-time monitoring of therapeutically relevant parameters. These devices could alert remote medical personnel in case of any anomaly and fully disintegrate in the body without a trace. Unfortunately, the need for a multitude of biodegradable electronic components (power supplies, wires, circuitry) in addition to the electrochemical biosensing interface has halted the arrival of fully bioresorbable electronically active medical devices. In recent years molybdenum (Mo) and tungsten (W) have drawn increasing attention as promising candidates for the fabrication of both energy-powered active (e.g., transistors and integrated circuits) and passive (e.g., resistors and capacitors) biodegradable electronic components. In this review, we discuss the latest Mo and W-based dissolvable devices for potential biomedical applications and how these soluble metals could pave the way towards next-generation fully transient implantable electronic systems. ispartof: SENSORS vol:22 issue:8 ispartof: location:Switzerland status: published

Background It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. Methods Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. Results Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ± 3.9 vs 7.0 ± 4.5 vs 9.7 ± 4.3 mm Hg (p = 0.054), mPAP: 39 ± 12 vs 48 ± 11 vs 51 ± 16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. Conclusions Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

Objective To estimate the prevalence of frailty in older adults in the IMIAS population, to examine associations between lifelong domestic violence and frailty and possible pathways to explain these associations. Methods A cross-sectional study with 2002 men and women in the International Mobility in Aging Study, aged between 65 and 74 years old living in five cities of Tirana (Albania), Natal (Brazil), Kingston and Saint-Hyacinthe (Canada), and Manizales (Colombia). Domestic physical and psychological violence by family and intimate partner was assessed by the Hurt, Insult, Threaten and Scream (HITS) scale. Fried’s phenotype was adopted to define frailty. Logistic regressions were fitted to estimate between frailty and lifelong violence. Mediation analyses using the Preacher and Hayes method was used to examine potential health pathways. Results Frailty prevalence varies across cities, being lowest in Saint-Hyacinthe and Kingston, and highest in women in Natal. Women had a higher prevalence in Tirana and Natal. Adjusting for age, sex, education and research city, those reporting childhood physical abuse (CPA) had higher odds of frailty (OR = 1.68; 95% CI: 1.01; 2.78); those who had been exposed to psychological violence by their intimate partner had also higher odds of frailty (OR = 2.07; 95% CI: 1.37; 3.12). CPA effect on frailty was totally mediated by chronic conditions and depression symptoms. Effects of psychological violence by intimate partner were partially mediated by chronic conditions and depression symptoms. Conclusions Childhood physical abuse and psychological violence during adulthood leave marks on life trajectory, being conducive to adverse health outcomes and frailty in old age.

Indoor air pollution assessment in work environments remains challenging due to a combination of logistic reasons and availability of costly instrumentation for data acquisition and post-processing. Existing literature focuses on energy production environments, hospitals, and less so on food production spaces. Studies on indoor air quality in bakeries are scarce or even absent. Motivated by this, the present study investigates indoor air quality in a bakery located in Bari province in South Italy, using a combination of approaches including analytical chemistry analyses and compu- tational fluid dynamics to reconstruct the air ventilation in response to air temperature gradients within the working environment. PM2.5 indoor samplings were collected every 6 h from 7 to 19 April 2013 in the proximity of two bakery ovens powered by gas and wood, respectively. For each sampling day, 4 PM2.5 samples were collected: from 3:00 to 9:00 h (first), from 9:00 to 13:30 h (second), from 14:00 to 21:00 h (third), and from 21:00 to 3:00 h (fourth). In total, 40 samples were collected. On each sample, several polycyclic aromatic hydrocarbons (PAHs) were deter- mined such as benzo[a]anthracene (228), benzo[b]fluoranthene (252), benzo[k]fluoranthene (252), benzo[a]pyrene (252), benzo[g,h,i]perylene (276), indeno[1,2,3-cd]pyrene (276), and dibenzo[a,h]anthracene (278), the main com- pounds of 16 priority US Environmental Protection Agency (US-EPA) PAHs in particulate phase. The PAH mean concentrations showed higher values during the first (from 3:00 to 9:00 h) and fourth (from 21:00 to 3:00 h) sampling intervals than the other two with benzo[a]pyrene mean values exceeding the Italian law limit of 1 ng/m3. Taking into account benzo[a]pyrene mean concentration for the first interval and the first plus the second one, which are the hours with the largest working activity, we have estimated that the baker and co-workers are exposed to a cancer risk of 4.3 × 10-7 and 5.8 × 10-7, respectively (these values are lower than US-EPA recommended guideline of 10-6). Our study was complemented by numerical analyses using state-of-the-art computational fluid dynamics to reconstruct at high resolution air movement from the various working places, i.e., the bakery and the selling area which were connected via a door. The numerical simulations were possible given that surface temperature using infrared thermog- raphy as well as air temperature was continuously recorded throughout the sampling acquisition. The use of this approach allowed us to estimate the transport and diffusion of benzo[a]pyrene from one area to the other thus complementing the point sampling information. Computational fluid dynamic simulation results confirm the presence of benzo[a]pyrene in the laboratory as obtained from the measurements and suggests its presence in the sales' area of the bakery with concentrations similar those found in the laboratory.

Few examples of the involvement of a single gene in idiopathic short stature have been described until now. Our aim was to identify the causative gene of proportionate short stature in a large family showing co-segregation of the phenotype with the reciprocal translocation t(10;15)(q22;q24). FISH mapping was carried out with BACs and long-range PCR probes to identify the smallest genomic regions harboring the translocation breakpoints. Real-Time RT-PCR was performed in blood after pre-amplification of target genes cDNA. The affected family members presented with a final height of between − 2.41 and − 4.18 SDS and very mild skeletal dysmorphisms. Growth rates of the proband and of her cousin, whose childhood and pre-pubertal bone age corresponded to the chronological age, showed a poor growth spurt during treatment with rhGH. However, their adult height was greater than that of their untreated mothers, suggesting efficacy of GH therapy. Breakpoint mapping revealed that the translocation t(10;15)(q22.3;q26.1) disrupts, on 15q, the ACAN gene at intron 1, decreasing its transcriptional expression. This is the first description of a chromosome rearrangement disrupting ACAN and leading to its haploinsufficiency. ACAN loss of function should be considered a potential underpinning of short patients who display a poor growth spurt and belong to families with autosomal dominant segregation of proportionate short stature. Besides this core phenotype, literature review suggests that advanced bone age, early onset osteochondritis dissecans, osteoarthritis, intervertebral disc disease as well as craniofacial dysmorphisms can be important suggestive phenotypes in affected families.

The occlusion of superficial femoris artery (SFA) is a common feature in peripheral vascular disease, so the profunda femoris artery (PFA) is a crucial collateral pathway for the perfusion of the lower limb. The purpose of this study is to discuss the safety, clinical, and hemodynamic efficacy of profundoplasty on the basis of limb salvage, patency, and freedom from reintervention rates. Furthermore, this study aims to identify the risk factors linked to the failure of the procedure.The study is based on a retrospective analysis of prospectively collected data of identified patients who underwent profundoplasty from March 2005 to October 2015. All patients showed a hemodynamic stenosis, extended from the posterior wall of the common femoral artery (CFA) into the origin of the PFA and concomitant occlusion of SFA. Endarterectomy with patch angioplasty was performed in all cases. In patients with concomitant iliac occlusive disease, a hybrid treatment was carried out to restore an adequate inflow through an endovascular approach.Seventy-four profundoplasty were performed during the study period. Isolate profundoplasty was performed in 56 cases (75.7%), while in the remaining 18 cases (24.3%), concomitant endovascular treatment of iliac lesions was performed. Hemodynamic success was achieved in 90.5% of the cases. The mean ankle-brachial index significantly improved, rising from 0.36 ± 0.17 preoperatively to 0.57 ± 0.20 postoperatively (P 0.001). The median follow-up period was 33 months. Primary patency rate was 98.5% at 12, 36, and 60 months. Freedom from reintervention rate was 97% at 1 year and 95.3% at 3 and 5 years. Limb salvage rate was 96.9% at 1 year and 92.7% at 3 and 5 years. Survival rates were 86%, 60%, and 47.4% at 1, 3, and 5 years, respectively. Multivariate analysis identified Rutherford class 5 or 6 lesions as the strongest predictors of major amputation or reintervention (odds ratio, 9.37; confidence interval: 0.98-89.27; P = 0.05).Profundoplasty is a durable, safe, and effective procedure in terms of clinical and hemodynamic results for patients characterized by occlusion of SFA and stenosis of CFA extended to profunda ostium. For patients with Rutherford category 5 and 6 ischemia, the only profundoplasty does not seem to be adequate, and concomitant distal bypass should be necessary to improve limb salvage and decrease reintervention rate.

A monolithic biosensing platform is presented for miniaturized amperometric electrochemical sensing in CMOS. The system consists of a fully integrated current readout circuit for differential current measurement as well as on-die sensors developed by growing platinum nanostructures (Pt-nanoS) on top of electrodes implemented with the top metal layer. The circuit is based on the switch–capacitor technique and includes pseudodifferential integrators for concurrent sampling of the differential sensor currents. The circuit further includes a differential to single converter and a programmable gain amplifier prior to an ADC. The system is fabricated in $\text{0.35}\ \mu \text{m}$ technology and measures current within $\pm \text{20}\ \mu \text{A}$ with minimum input-referred noise of $\text{0.47}\ \text{pA}$ and consumes $\text{9.3}\ \text{mW}$ from a $\text{3.3}\ \text{V}$ supply. Differential sensing for nanostructured sensors is proposed to build highly sensitive and offset-free sensors for metabolite detection. This is successfully tested for bio-nano-sensors for the measurement of glucose in submilli molar concentrations with the proposed readout IC. The on-die electrodes are nanostructured and cyclic voltammetry run successfully through the readout IC to demonstrate detection of $\text{H}_2\text{O}_2$ .

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine. Under the same conditions the activity of mTORC1 is inhibited. Decreased cell content of branched chain amino acids and mTORC1 inhibition are observed in most of the other cell lines upon incubation with GPNA. It is concluded that GPNA hinders the uptake of essential amino acids through system L transporters and lowers their cell content.

A 77-year-old male patient presented with a symptomatic, 66-mm pararenal aortic aneurysm. The patient was classified as unsuitable for open surgery due to significant comorbidities. Fenestrated or branched endografts were contraindicated due to the poor iliac access (6 mm diameter). A double Nellix with chimney endovascular aneurysm sealing (ChEVAS) technique was selected to exclude the pararenal aortic aneurysm and to preserve renal arteries and the superior mesenteric artery. Technical preplanning considered the ideal proximal landing zone to be close to the origin of the almost occluded celiac trunk and the distal common iliac arteries as the ideal distal landing zone. The total length of the aorta to cover was estimated as >180 mm, requiring 2 aortic EVAS systems, bilaterally overlapped. Technical success was achieved, and the patient was discharged on postoperative day 8 in good general condition. Successful aneurysm exclusion and target vessel patency without endoleak or stent-graft kinking or migration were confirmed at angio-computed tomography at 6 months.

In cultured human fibroblasts, SNAT transporters (System A) account for the accumulation of non-essential neutral amino acids, are adaptively up-regulated upon amino acid deprivation and play a major role in cell volume recovery upon hypertonic stress. No information is instead available on the expression and activity of SNAT transporters in human bone marrow mesenchymal stromal cells (MSC), although they are increasingly investigated for their staminal and immunomodulatory properties and used for several therapeutic applications. The uptake of glutamine and proline, two substrates of SNAT1 and SNAT2 transporters, was measured in primary human MSC and an MSC line. The amino acid analogue MeAIB, a specific substrate of these carriers, has been used to selectively inhibit SNAT-dependent transport of glutamine and, through its sodium-dependent transport, as an indicator of SNAT1/2 activity. SNAT1/2 expression and localization were assessed with RT-PCR and confocal microscopy, respectively. Cell volume was assessed from urea distribution space. In all these experiments, primary human fibroblasts were used as the positive control for SNAT expression and activity. Compared with fibroblasts, MSC have a lower SNAT1 expression and hardly detectable membrane localization of both SNAT1 and SNAT2. Moreover, they exhibit no sodium-dependent MeAIB uptake or MeAIB-inhibitable glutamine transport, and exhibit a lower ability to accumulate glutamine and proline than fibroblasts. MSC exhibited an only marginal increase in MeAIB transport upon amino acid starvation and did not recover cell volume after hypertonic stress. In conclusion, the activity of SNAT transporters is low in human MSC. MSC adaptation to amino acid shortage is expected to rely on intracellular synthesis, given the absence of an effective up-regulation of the SNAT transporters.

Atherosclerosis is a progressive vascular disease representing the primary cause of morbidity and mortality in developed countries. Formerly, atherosclerosis was considered as a mere passive accumulation of lipids in blood vessels. However, it is now clear that atherosclerosis is a complex and multifactorial disease, in which the involvement of immune cells and inflammation play a key role. A variety of studies have shown that autophagy—a cellular catalytic mechanism able to remove injured cytoplasmic components in response to cellular stress—may be proatherogenic. So far, in this context, its role has been investigated in smooth muscle cells, macrophages, and endothelial cells, while the function of this catabolic protective process in lymphocyte functionality has been overlooked. The few studies carried out so far, however, suggested that autophagy modulation in lymphocyte subsets may be functionally related to plaque formation and development. Therefore, in this research, we aimed at better clarifying the role of lymphocyte subsets, mainly regulatory T cells (Tregs), in human atherosclerotic plaques and in animal models of atherosclerosis investigating the contribution of autophagy on immune cell homeostasis. Here, we investigate basal autophagy in a mouse model of atherosclerosis, apolipoprotein E (ApoE)-knockout (KO) mice, and we analyze the role of autophagy in driving Tregs polarization. We observed defective maturation of Tregs from ApoE-KO mice in response to tumor growth factor-β (TGFβ). TGFβ is a well-known autophagy inducer, and Tregs maturation defects in ApoE-KO mice seem to be related to autophagy impairment. In this work, we propose that autophagy underlies Tregs maturation, advocating that the study of this process in atherosclerosis may open new therapeutic strategies.

Length and aspect ratio represent important toxicity determinants of fibrous nanomaterials. We have previously shown that anatase TiO

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.

Home monitoring is the most practical means of collecting sleep data in large-scale research investigations. Because the portion of recording time with poor-quality data is higher than in attended polysomnography, a quantitative assessment of the quality of each signal should be recommended. Currently, only qualitative or semi-quantitative assessments are carried out, likely because of the lack of computer-based applications to carry out this task efficiently. This paper presents an innovative computer-assisted procedure designed to perform a quantitative quality assessment of standard respiratory signals recorded by Type 2 and Type 3 portable sleep monitors. The proposed system allows to assess the quality (good versus bad) of consecutive 1-min segments of thoraco-abdominal movements, oronasal, nasal airflow and oxygen saturation through an automatic classifier. The performance of the classifier was evaluated in a sample of 30 unattended polysomnography recordings, comparing the computer output with the consensus of two expert scorers. The difference (computer versus scorers) in the percentage of good-quality segments was on average very small, ranging from -3.1% (abdominal movements) to 0.8% (nasal flow), with an average total classification accuracy from 90.2 (oronasal flow) to 94.9 (nasal flow), a Sensitivity from 0.93 (oronasal flow) to 0.98 (nasal flow), and a Specificity from 0.74 (nasal flow) to 0.86 (abdominal movements). In practical applications, the scorer can run a check-and-edit procedure, further improving the classification accuracy. Considering a sample of 270 unattended polysomnography recordings (recording time: 545 ± 44 min), the average time taken for the check-and-edit procedure of each recording was 6.9 ± 2.1 min for all respiratory signals.

The aim of this study was to evaluate CD25

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) frequently cause patients with COPD to access the emergency department and have a negative impact on the course of the disease. The objectives of our study were: 1) describing the socio-demographic and clinical characteristics, and the clinical management, of patients with AECOPD, when they present to the emergency department; and 2) estimating the costs related to the management of these patients. We conducted a retrospective cohort study in Italy, collecting data on 4396 patients, from 34 centres. Patients had a mean (SD) age of 76,6 (10.6) years, and 61.2% of them where males. >70% of the patients had a moderate to very high comorbidity burden, and heart failure was present in 26.4% of the cohort. The 64.6% of patients were admitted to hospital wards, with a mean (SD) length of stay of 10.8 (9.8) days. The estimated cost per patient was 2617 €. Conclusions: Patients attending the ED for an AECOPD are old and present important comorbidities. The rate of admission is high, and costs are remarkable. © 2018 European Federation of Internal Medicine

Background The incidence and distribution of primary glomerulonephropathies vary throughout the world and by race and ethnicity. We sought to evaluate the distribution of primary glomerulonephropathies among a large racially and ethnically diverse population of the United States. Study Design Case series from January 1, 2000, through December 31, 2011. Setting & Participants Adults (aged ≥ 18 years) of an integrated health system who underwent native kidney biopsy and had kidney biopsy findings demonstrating focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), and other. Outcomes Rates and characteristics of the most common primary glomerulonephropathies overall and by race and ethnicity. Results 2,501 patients with primary glomerulonephropathy were identified, with a mean age 50.6 years, 45.7% women, 36.1% Hispanics, 31.2% non-Hispanic whites, 17.4% blacks, and 12.4% Asians. FSGS was the most common glomerulonephropathy (38.9%) across all race and ethnic groups, followed by MGN (12.7%), MCD (11.0%), IgAN (10.2%), and other (27.3%). The FSGS category had the greatest proportion of blacks, and patients with FSGS had the highest rate of poverty. IgAN was the second most common glomerulonephropathy among Asians (28.6%), whereas it was 1.2% among blacks. Patients with MGN presented with the highest proteinuria (protein excretion, 8.3g) whereas patients with FSGS had the highest creatinine levels (2.6mg/dL). Overall glomerulonephropathy rates increased annually in our 12-year observation period, driven by FSGS (2.7 cases/100,000) and IgAN (0.7 cases/100,000). MGN and MCD rates remained flat. Limitations Missing data for urine albumin and sediment, indication bias in performing kidney biopsies, and inexact classification of primary versus secondary disease. Conclusions Among a racially and ethnically diverse cohort from a single geographical area and similar environment, FSGS was the most common glomerulonephropathy, but there was variability of other glomerulonephropathies based on race and ethnicity.

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine (Gln) transporter ASCT2, but recent studies have demonstrated that it is also able to inhibit other sodium-dependent and independent amino acid transporters. Moreover, GPNA is a well known substrate of the enzyme γ-glutamyltransferase (GGT). Our aim was to evaluate the effect of GGT-mediated GPNA catabolism on cell viability and Gln transport. The GGT-catalyzed hydrolysis of GPNA produced cytotoxic effects in lung cancer A549 cells, resulting from the release of metabolite p-nitroaniline (PNA) rather than from the inhibition of Gln uptake. Interestingly, compounds like valproic acid, verapamil and reversan were able to increase the cytotoxicity of GPNA and PNA, suggesting a key role of intracellular detoxification mechanisms. Our data indicate that the mechanism of action of GPNA is more complex than believed, and further confirm the poor specificity of GPNA as an inhibitor of Gln transport. Different factors may modulate the final effects of GPNA, ranging from GGT and ASCT2 expression to intracellular defenses against xenobiotics. Thus, other strategies - such as a genetic suppression of ASCT2 or the identification of new specific inhibitors - should be preferred when inhibition of ASCT2 function is required.

Acute aortic occlusion is a rare but potentially devastating clinical event, which requires a prompt diagnosis and emergency treatment. Only 5 cases of native thoracic aorta acute occlusion have so far been reported with different pathologic causes. The clinical features depend on the level of occlusion. Sometimes the diagnosis could be misinterpreted as a stroke or other diseases of the central nervous system. This could lead to a delay in the diagnosis and revascularization procedure, followed by a morbidity or mortality increase. Open surgery has been considered the first-line approach. This study is of a female patient suffering from acute descending thoracic aorta occlusion undergoing, for the first time to our knowledge, endovascular surgical treatment.

Lithium is the main drug for the treatment of mood disorders. Due to its narrow therapeutic window, Therapeutic Drug Monitoring (TDM) is a norm during therapy in order to avoid adverse effects. Consequently, patients are obliged to frequent check-ups in hospitals to determine their serum concentration and optimize accordingly the drug dose. Wearable sensors have attracted a growing interest in the research community in recent years owing to their promising impact in personalized healthcare. In particular, sweat diagnosis has seen an enormous expansion and is currently entering the market thanks to the large availability and simple collection of this fluid. In this paper a novel approach for non-invasive decentralized monitoring of lithium drug concentration through sweat analysis is proposed for the first time. An all-solid-state Ion- Selective Electrode (ISE) with a nanostructured Solid-Contact (SC) is used to detect lithium ions in sweat. The sensor offers near-Nernstian behaviour (57:6±2:1 mV/decade) in the concentration range of interest. In addition, it shows fast response (15-30 s), good reversibility and small potential drift over time. A wide pH stability window (pH 4-12) is also proved.

Interaction between cigarette smoking and efficacy of oral antiplatelet drugs is not definitely elucidated. We evaluated the effects of cigarette smoking on platelet reactivity in patients receiving different oral P2Y12 antagonists after myocardial infarction (MI) and drug-eluting stent (DES) implantation. Two-hundred-five consecutive current smokers receiving DES implantation after ST-segment elevation MI were enrolled. All patients were aspirin-treated and were on chronic therapy with clopidogrel (N = 59), prasugrel (N = 71) or ticagrelor (N = 75); by protocol, all patients at baseline had no high on-treatment platelet reactivity by the VerifyNow P2Y12 assay. Platelet reactivity, expressed by P2Y12 reaction units (PRU), was measured in all patients at baseline (T0), after a 15-day period of smoking cessation (T1) and after further 15 days of smoking resumption (T2). In the overall population there was a modest, albeit significant, reduction of PRU values from T0 to T1 (from 173 ± 14 to 165 ± 17, P < 0.0001); resumption of cigarette smoking was associated with re-increase of platelet reactivity (from 165 ± 17 at T1 to 170 ± 17 at T2, P = 0.0002). These variations were consistent in the subgroups receiving clopidogrel, prasugrel or ticagrelor and were irrespective of the number of cigarettes smoked. In conclusion, cigarette smoking weakly influences antiplatelet effects of oral P2Y12 inhibition and this was irrespective of the type of antiplatelet agent; thus, interaction between cigarette smoking and efficacy of oral antiplatelet drugs is modest and unlikely translates into clinical effects (ClinicalTrials.gov Identifier: NCT02026713).

Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer., Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.