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We study a class of variational problems involving both bulk and interface energies. The bulk energy is of Dirichlet type albeit of very general form allowing the dependence from the unknown variable u and the position x. We employ the regularity theory of $$\Lambda $$ Λ -minimizers to study the regularity of the free interface. The hallmark of the paper is the mild regularity assumption concerning the dependence of the coefficients with respect to x and u that is of Hölder type.

Bone is an extraordinary biological material able to modify dynamically its outer shape and inner microstructure in response to chemo-mechanical stimuli coming from the environment adapting its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness. To date, many theories and mathematical models have been proposed by several authors to describe the remodeling phenomenon, all approaches starting from the adaptive elasticity and the bone maintenance theories. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford’s law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields, in this way affecting growth and remodeling of the bone tissue. Two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, and a real study case of a patient subject to total hip replacement, and CT scanned at 24 hours after surgery and at 1 year post-surgery have been considered. It has to note that the proposed model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium-long term, unpredictable with the standard approach. Although limitations still characterize some hypotheses at the basis of the present approach, the proposed model overcomes the intrinsic - and unrealistic - independence of the bone remodeling from the stress sign and from the indirect effect of stress gradients driving nutrients through the flow of the fluid content in the tissue, allowing to predict important spatial asymmetries in bone mass density, so paving the way to more reliable mechanobiological strategies and engineering tools for the faithful prediction of bone remodeling, with implications in diagnosis of risk fracture, optimal design of scaffolds and bone prostheses.

In the present work, the response of composite hybrid laminates made of carbon and glass fibers in different stacking configurations was tested under low-velocity impact loads. Experimental drop impact tests were conducted on three different stacking sequences and three rising impact energy levels. The results from the tests were assumed for the development and validation of a numerical impact model reproducing for each stacking sequence and all the impact energy levels, the laminates impact response. The validated model investigated the occurred damage mechanisms, their distribution in the panel thickness and their extension on the plane of the laminate. Depending on the stacking sequence and the impact energy level, the energy absorption capacity was related to the dominant damage mechanism. The percentage contribution of interlaminar and intralaminar damages was presented and conclusions were drawn about the influence of stacking sequences on energy absorption and damage characteristics.

The impact of COVID-19 changed the use and delivery of health care services, requiring an abrupt shift in treatment and staffing models 1,2. This is particularly salient in youth acute and intensive treatment services (AITS), including inpatient psychiatric hospitals (IPH), intensive outpatient programs (IOP), and partial hospitalization programs (PHP), because of challenging issues of maintaining high-quality care and a safe therapeutic milieu during increased demand for acute services,3 all while limiting transmission of COVID-19 on locked units, in close quarters, and for youths traveling back and forth to day-programs. Over the past year, AITS adapted and evolved without the ability to pause services and plan, increase staffing, or allocate additional resources. This article discusses themes of changes made based on more than 20 facilities across the United States through the American Psychological Association Child and Adolescent Psychology Division’s Acute, Intensive, and Residential Service Special Interest Group.4 These facilities include psychiatric inpatient units and day-treatment programs. We discuss lessons learned from these changes, the need for evaluating these changes, and application of these lessons in future crises.

Background There is a positive continuous association between Lipoprotein(a) (Lp[a]) levels and the risk of recurrent ischemic events in patients with recent myocardial infarction (MI). However, the prognostic significance of the association between high Lp(a) levels and diabetes has been poorly investigated after MI. Purpose The aim of this study was to evaluate the association of Lp(a) levels with the long-term risk of adverse events in post-MI patients, and to investigate whether diabetes may influence this association. Methods Consecutive MI patients who underwent urgent/emergent coronary angiography at our Institution from February 2013 to June 2019 were prospectively collected. Lp(a) serum concentrations was expressed for increasing range values (≤10, >10–30, >30–50, >50–70, and ≥70 mg/dL). The primary outcome was the recurrence of MI; the secondary outcome was all-cause death. The propensity score weighting technique was used to account for potential confounding between patients with and without diabetes. Results The study population consisted of 1018 post-MI patients (median age: 63 years; 76% males). Diabetes was reported in 280 patients (27.5%). The median value of Lp(a) was 10 mg/dL, and patients with diabetes showed significantly lower Lp(a) levels than patients without diabetes (p=0.025). At a median follow-up of 1121 days, the primary outcome was reported in 109 patients (10.7%), and the secondary outcome in 100 (9.8%). After propensity score weighting, there was a significant association between increasing Lp(a) range values and the primary outcome both in the overall population (p trend = 0.030) and in non-diabetic patients (p trend = 0.009), but not in diabetics. Conversely, no significant association with the risk of all-cause mortality across increasing Lp(a) categories both in the overall population and in the study groups according to the presence or not of diabetes was found. Compared with the lowest Lp(a) category, Lp(a) plasma levels >70 mg/dL were independently associated with the risk of recurrent MI (HR: 3.222; 95% CI, 1.225–8.478, p=0.018) and all-cause death (HR: 2.656; 95% CI, 1.009–6.991, p=0.048) in non-diabetic patients, but not in diabetics. Conclusions In this real-world post-MI population, Lp(a) serum levels were lower in diabetic than in non-diabetic patients. Increasing Lp(a) levels were significantly associated with the risk of recurrent MI, and very high Lp(a) serum concentration (>70 mg/dL) independently predicted recurrent MI and death in non-diabetic patients, but not in diabetics. These results reinforce the importance of routine assessment of Lp(a) levels after MI, particularly in patients without diabetes. Funding Acknowledgement Type of funding sources: None.

Background The Academic Research Consortium for High Bleeding Risk (ARC–HBR) has recently proposed, by consensus, twenty clinical criteria for the assessment of the bleeding risk after percutaneous coronary intervention (PCI). A major criterion was defined as any individual clinical condition conferring in isolation a risk for major bleeding ≥4% up to 1 year after PCI; instead, a minor criterion was considered to confer a bleeding risk of Methods MEDLINE, COCHRANE, Web of Sciences, and SCOPUS were searched for studies aimed at validating the ARC–HBR criteria in patients treated with PCI. The primary outcome measure of this meta–analysis was major bleeding. Results The analysis included 10 studies encompassing 67,862 patients undergoing PCI; the HBR definition was fulfilled in 44.7% of the cases. The risk of major bleeding was significantly higher in HBR vs. Non–HBR group (RR, 2.56, 95% CI 2.28–2.89). The average C–statistic was 0.64 (95% CI 0.60–0.68), indicating modest discrimination. The risk of intracranial hemorrhage, gastrointestinal bleeding, fatal bleeding, ischaemic stroke, cardiac death and all–cause death was higher in HBR vs. Non–HBR group. Despite a higher incidence of myocardial infarction and stent thrombosis in patients deemed at HBR, the rate of target lesion revascularization was comparable between groups (RR, 1.01, 95% CI 0.88–1.16). When assessed in isolation, the mean cumulative incidence of major bleeding at 1 year exceeded the cut–off value of 4% for all the major criteria and for two out of six minor criteria, including age ≥75 years and moderate chronic kidney disease (CKD) (Figure). Conclusion The ARC–HBR definition identifies patients at higher risk of major bleeding and other adverse cardiovascular events after PCI. Almost all major criteria, but also two of the minor criteria, were individually associated with rates of major bleeding above 4% thus fulfilling the definition of major HBR criteria. These findings corroborate the ability of ARC–HBR major criteria in identifying PCI patients who are more likely to develop adverse events, but also suggest caution in the decision making of patients with isolated minor criteria, including age≥75 years and moderate CKD.

Aims To describe the baseline clinical, laboratory and angiographic characteristics of patients with acute myocardial infarction (MI) according to the presence or not of diabetes mellitus (DM), and to evaluate if DM may influence the effect of lipoprotein(a) [Lp(a)] serum level on long–term outcome in this very high–risk population. Methods This was a retrospective, single–center, study including consecutive patients admitted with MI diagnosis between January 1, 2017, and December 31, 2020. The availability of data on baseline Lp(a) serum level was considered as an inclusion criterion. The study population was divided into two groups according to the presence or not of DM. The Lp(a) value of 50 mg/dL was used to test the hypothesis of a different effect of Lp(a) on the clinical outcome of patients with or without DM. The primary study outcome was all–cause death at 3–year follow–up. Results The study population included 997 patients (mean age 63.7±13.5 years; 75.7% were males). Diabetes was reported in 280 (28.1%) patients. DM patients were older than those without DM (67.8±12.1 vs. 62.0±13.7 years, p Conclusion In this MI population, Lp(a) was independently associated with long–term mortality in patients without DM, but not in patients with DM. Whether DM can modify the effect of Lp(a) on clinical outcome after MI requires confirmation by larger prospective studies.

American Indian (AI) and Indigenous peoples utilize traditional medicine/healing (TM/H) for health and well-being. Allopathic health care practitioners (HCPs) receive minimal training and education on TM/H and its application and integration into health care settings. Lack of knowledge and practice guidelines on how to navigate these 2 health care perspectives (allopathic and traditional) creates uncertainties in the treatment of AI and Indigenous peoples. Such conflicts can undermine patient autonomy and result in culturally incongruent practice. This article presents a case study showcasing suggestions for how HCPs can direct clinical decision making when working with AI/Indigenous patients who utilize TM/H. The article argues that health professions education institutions and HCPs must dedicate effort to expanding awareness of and education about TM/H to enhance the delivery of evidence-based and integrated clinical treatment for AI/Indigenous patients.

Background Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies. Methods This prospective pilot randomized French multicenter study aimed to compare anti–T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included. Results Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%–37.1%) and 18.8% (95% CI, 8.9%–37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%–34.8%) and 28.2% (95% CI, 14.2%–51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell–mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups. Conclusion This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution., Graphical abstract

Funding Acknowledgements Type of funding sources: None. Backgrounds although right ventricular (RV) systolic dysfunction seems to be associated with adverse outcome after transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip system, the prognostic value of RV free wall strain in this setting has not been yet investigated. Purpose aim of this study is to evaluate RV free wall strain as predictor of outcome in patients with severe or moderate-to-severe functional MR undergoing TEER and its prognostic role compared with tricuspid annular plane systolic excursion (TAPSE). Methods 102 patients [73 (IQR 66.8-77.0) years, 73 males (71.6%)] were retrospectively selected from March 2012 to February 2021. Echocardiograms were performed by using General Electric machines. RV free wall strain was assessed through RV modified apical 4-chamber view, setting the region of interest to minimum size (Figure 1). Values of RV free wall strain >-20% were recognized as abnormal. We considered a composite endpoint including rehospitalization for heart failure (HF) and overall death as primary outcome. Secondary outcomes were overall death, cardiac death and rehospitalization for HF. All patients were assessed at the longest available follow-up [median 22.1 (IQR 9.7-49.3) months]. Results primary outcome was found in 60 (58.8%) patients, while secondary outcomes, i.e. overall death, cardiac death and rehospitalization for HF, were found respectively in 50 (50.0%), 31 (30.4%) and 36 (35.3%) patients. Mean TAPSE was 16.7 ± 4.0 mm and mean RV free wall strain was -16.9 ± 6.0%. At univariable analysis both TAPSE (HR 0.907, CI 0.848-0.970, p value 0.004) and RV free wall strain (HR 0.937, CI 0.897-0.979, p value 0.004) were significantly associated with the primary outcome. Kaplan-Meier survival curves showed that patients with TAPSE -20% also showed a lower survival free from the composite outcome compared with patients with RV free wall strain ≤-20% (Log Rank 0.004). Among patients with preserved RV systolic longitudinal function as indicated by TAPSE ≥17 mm, subjects with RV free wall strain >-20% had a significantly higher incidence of the composite outcome compare with those with RV free wall strain ≤-20% (Log-Rank = 0.008, Figure 2). Conversely, no difference was found among patients with TAPSE Conclusions RV dysfunction assessed either by TAPSE and RV free wall strain is associated with poorer outcome in patients with severe or moderate-to-severe functional MR undergoing TEER. Compared with TAPSE, RV free wall strain seems to be superior in identifying patients at higher risk of adverse events during follow-up. Our data encourage the use of this speckle tracking-derived echocardiographic parameter in routinely evaluation of patients with functional MR candidate for TEER. Abstract Figure. Abstract Figure 2

Growth hormone-releasing peptide-6 (GHRP-6) is part of a group of small synthetic peptides with potent GH-releasing activity that have gained attention in the last two decades by virtue of their cyto- and cardioprotective effects. Despite numerous preclinical studies highlighting the potential cardiovascular benefits of GHRP-6, confirmation of clinical efficacy is still awaited. Recent advances in transdermal drug delivery systems have been made to address challenges related to the poor skin permeation rate of peptides by using pain-free microneedle (MN) devices. Accordingly, highly sensitive and validated analytical methods are required for the potential clinical translation of MN-based peptides. The ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) methods developed in this study aimed to quantify GHRP-6 in biological matrices (plasma, skin) and dissolving polymeric MNs. UHPLC/MS-MS method detection limits of 0.1, 1.1, 0.9 and 1.5 ng/mL were achieved in neat solution, plasma, MN polymer solution, and skin matrices, respectively. Method validation also involved assessment of precision, accuracy, limits of quantification, linearity of matched calibration curves (R2 > 0.990), extraction recovery, matrix effect, stability studies, selectivity, and carry-over effect. Additionally, quality control samples were analyzed at three concentration levels to determine recovery (85–109%) and accuracy/bias (3.2–14.7%). Intra- and inter-day precision were within the range of acceptance (RSDs of 3.0–13.9% and 0.4–14.5%, respectively). The validity and applicability of such methods were successfully demonstrated for transdermal GHRP-6 delivery using GHRP-6-loaded MN patches applied to pig skin.

Background In cardiac amyloidosis the application of Speckle Tracking Echocardiography allows to identify a specific left ventricular (LV) longitudinal strain (LS) pattern characterized by “apical sparing”, with a prominent involvement of basal and middle segments and normal LS of apical cap. The pattern of regional LS has been never investigated in monoclonal gammopathy of undetermined significance (MGUS), a condition which can predispose to cardiac amyloidosis. Purpose To compare LV regional LS patterns and LS base-to-apex behaviour of patients affected by MGUS in comparison with healthy subjects. Methods We enrolled 40 patients affected by MGUS (M/F=20/20; age 62.6±13.8 years), asymptomatic for cardiac symptoms, and a control group of 40 healthy subjects, matched for sex and age. Nineteen (47%) MGUS patients showed prevalent free K light chain and 21 (53%) had prevalent free λ light chain. Participants underwent standard echo-Doppler exam, including Speckle Tracking of the three apical views. Global longitudinal strain (GLS), the average LS of six basal (BLS), six middle (MLS), and six apical (ALS) segments (considered in absolute values) and relative regional strain ratio RRSR [=ALS/(BLS+MLS)] were computed. Exclusion criteria were overt heart failure, LV ejection fraction Results The two groups were comparable for body mass index, blood pressure and heart rate. LV mass index, relative wall thickness, left atrial volume index and Doppler-derived LV diastolic parameters did not differ significantly between the two groups. LV ejection fraction was also similar in MGUS and healthy controls. GLS resulted significantly lower in MGUS group than in controls (20.5±3.0 vs. 22.4±2.0%, p1. The figure depicts a LS bull'eye of a MGUS patient showing the prominent involvement of LV basal segments. Conclusions In presence of a normal LV ejection fraction, MGUS patients show a subclinical LV longitudinal systolic dysfunction. This is testified by a reduction of GLS and of regional LS which involves mainly LV basal segments, without substantial changes of relative regional strain ratio. LV regional longitudinal dysfunction could be useful to monitor LV myocardial mechanics during follow-up of MGUS patients. LS bull's eye in a MGUS patient Funding Acknowledgement Type of funding source: None

The foraging success of orb-web spiders depends primarily on the structure and maintenance of their webs. The purpose of this study was to examine how the presence and degree of web damage affected web-building responses in Zygiella x-notata. Part 1 of the study investigated the severity of damage with: a control, a partial web damage group, and a complete web damage group. Part 2 investigated frequency of damage over a 5-day period with: a control group, an infrequent web damage group, and a frequent web damage group. Four spiders were allocated randomly to each experimental group, and four trials for each were conducted. Results suggested that spiders were unlikely to relocate, regardless of the type of web damage that occurred. Web sizes exhibited a decreasing trend for all experimental groups after web damage, except for controls and partial damage groups, with the largest decreases seen in frequent and complete damage groups. Anchor thread count increased after partial and complete damage; however, it decreased after damage in both repetitive web damage groups. Overall, these preliminary findings suggest that web-building spiders will likely rebuild instead of relocate in areas where damage occurs to their webs. When the damage is partial and non-repetitive, they expend more energy repairing and reinforcing their webs. However, when faced with repetitive and complete damage, their behavior is an adaptation to reduce the amount of energy expended in web repair.

DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of broadly acting, small molecule-based demethylating drugs with significant side-effects and toxicities. To allow for targeted DNA demethylation, we integrated two nucleic acid-based approaches: DNMT1 interacting RNA (DiR) and RNA aptamer strategy. By combining the RNA inherent capabilities of inhibiting DNMT1 with an aptamer platform, we generated a first-in-class DNMT1-targeted approach – aptaDiR. Molecular modelling of RNA-DNMT1 complexes coupled with biochemical and cellular assays enabled the identification and characterization of aptaDiR. This RNA bio-drug is able to block DNA methylation, impair cancer cell viability and inhibit tumour growth in vivo. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved non-specific hypomethylating protocols, which will greatly improve clinical intervention on DNA methylation.

Autobiographical memory studies conducted with narrative methods are onerous, requiring significant resources in time and labor. We have created a semi-automated process that allows autobiographical transcribing and scoring methods to be streamlined. Our paper focuses on the Autobiographical Interview (AI; Levine, Svoboda, Hay, Winocur,Moscovitch, Psychology and Aging, 17, 677-89, 2002), but this method can be adapted for other narrative protocols. Specifically, here we lay out a procedure that guides researchers through the four main phases of the autobiographical narrative pipeline: (1) data collection, (2) transcribing, (3) scoring, and (4) analysis. First, we provide recommendations for incorporating transcription software to augment human transcribing. We then introduce an electronic scoring procedure for tagging narratives for scoring that incorporates the traditional AI scoring method with basic keyboard shortcuts in Microsoft Word. Finally, we provide a Python script that can be used to automate counting of scored transcripts. This method accelerates the time it takes to conduct a narrative study and reduces the opportunity for error in narrative quantification. Available open access on GitHub ( https://github.com/cMadan/scoreAI ), our pipeline makes narrative methods more accessible for future research.

Background Hyperuricemia has been reported to accelerate the occurrence and worsening of cardiovascular disease, being a risk factor for coronary heart disease and cardiac mortality. Elevated uric acid (UA) is also associated with left ventricular (LV) hypertrophy and with LV diastolic dysfunction. The effect of hyperuricemia (HU) on LV systolic function is still unclear. Purpose Aim of our study was to evaluate the impact of elevated UA serum levels on LV systolic function, also evaluating longitudinal deformation, in a population of hypertensive patients. Methods We enrolled 160 treated hypertensive patients (M/F = 104/56, age 58.2 ± 13.3 years, blood pressure = 136.7 ± 16.8/81.3 ± 10.9 mmHg), who underwent standard echo-Doppler exam, including speckle tracking quantification of global longitudinal strain (GLS, considered in absolute value). HU was defined as UA≥7 mg/dL and the study population was divided in two groups: patients with (n = 63) and without (n = 97) HU. Exclusion criteria were coronary artery disease, overt heart failure, hemodynamically significant valve heart disease, primary cardiomyopathies, permanent atrial fibrillation and inadequate echo imaging. Results The two groups were comparable for sex prevalence, blood pressure and heart rate. Patients with HU were older and had higher body mass index (BMI) (both p Conclusions In hypertensive patients with multiple cardiovascular risk factors, the presence of HU is associated with LV diastolic and systolic dysfunction. Serum UA levels and GLS resulted independently associated even after adjusting for several clinical and echo confounders. Acid uric might be considered as an independent marker of early LV dysfunction, able to identify hypertensive patients at increased risk for heart failure. Abstract P658 Figure. Relation between uric acid and GLS

Background Overweight and obesity are related to the risk of new-onset atrial fibrillation (AF). Peak atrial longitudinal strain (PALS) is an advanced echocardiographic parameter of left atrial (LA) function with a recognized diagnostic and prognostic role in both the general population and AF. Purpose To investigate the impact of body mass index (BMI) on LA function by utilizing standard and advanced echocardiography in patients with non-valvular AF. Methods In the NeAfib-Echo registry, 395 consecutive adult patients with non-valvular AF (F/M: 175/220; mean age 70.6 ± 11 years, BMI: 27.8 ± 5.6 kg/m²) were enrolled. 215 patients (54.1%) had permanent/persistent AF (prAF) and 178 (45.9%) had paroxysmal AF (pxAF). Anthropometric parameters and blood pressure (BP) were recorded and CHA2DS2VASc score was calculated. Patients underwent a complete echo-Doppler exam, including determination of PALS and left ventricular (LV) global longitudinal strain (GLS) (both reported in absolute values). The overall population was divided according to BMI tertiles: first tertile 29.3 Kg/m² (n = 130). Results No significant difference of sex prevalence, age, systolic BP and heart rate was found among the three BMI tertiles, whereas diastolic BP was higher in the third tertile (p Conclusions In patients with non valvular AF, overweight and obesity exert a detrimental effect on LA function as testified by the gradual PALS reduction with the increase of BMI tertiles. BMI is associated with PALS independently of several confounders including CHA2DS2VASc. Besides CHA2DS2VASc score, BMI could be considered as an additional factor for evaluating cardiovascular risk in non valvular AF. Abstract P814 Figure. Relation between BMI and PALS

Background In non-valvular atrial fibrillation (AF) patients, risk stratification scores such as CHA2DS2VASc and HASBLED allow the prediction of thromboembolic and bleeding risks, respectively. However, no risk score for the prediction of AF recurrence has been yet validated. Purpose To evaluate the mayor anthropometric and echocardiographic determinants of AF recurrence in non-valvular paroxysmal AF patients at 1 year follow-up. Methods Among 395 consecutive adult patients with non valvular AF enrolled in the Neapolitan Atrial Fibrillation (NeAfi) Echo registry, 177 (F/M = 87/90, age = 66.5± 11.9 years) had paroxismal AF and underwent 1-year follow-up. Fifteen patients had AF recurrence. Anthropometric parameters and blood pressure (BP) were recorded and CHA2DS2VASc and HASBLED scores were calculated. At baseline, patients underwent a comprehensive echo-Doppler exam, including quantification of left atrial (LA) size measurements, peak atrial longitudinal strain (PALS) and left ventricular (LV) global longitudinal strain (GLS). Binary logistic regression analysis was used to establish a mathematical model of the relationship between the variables and AF recurrence. The covariates for regression analysis were chosen as potential confounding factors based on their significance in independent T test analyses for continuous variables of chi-square for dichotomous variables, or on their biological plausibility. Results AF recurrence was higher in male than in female patients (14.4 vs 2.3%, p = 0.008). Patients with AF recurrence had similar body mass index, systolic and diastolic BP and heart rate compared to those without. The two groups were similar for LV end-systolic and end-diastolic volumes, ejection fraction, LV mass index, diastolic indexes, pulmonary artery systolic pressure and GLS. LA diameter (p = 0.235) and PALS (p = 0.375) were also similar between the two groups, whereas LA volume index (LAVi) was greater in patients experiencing AF recurrence (45.5 ± 15.7 vs. 36.7 ± 10.4 ml/m², p = 0.003). Binomial multiple regression analysis model explained 25% (Nagelkerke R²) of the variance in AF recurrence and correctly classified 95.0% of cases. Males were 8.9 times more likely to exhibit AF recurrence than females (p = 0.04). Greater LAVi was associated with an increased likelihood of exhibiting AF recurrence (OR = 1.07, p = 0.03), whereas CHA2DS2VASc >1 in men and >2 in women, HASBLED >3 and greater LA diameter or lower PALS did not add significant information to the model. Conclusions Male gender and, with a lower extent, LAVi appear to be major determinants of AF recurrence in non-valvular paroxysmal AF. The quantification of PALS does not seem to add valuable information in the prediction of recurrent AF.

Organogels are semi-solid systems with an organic liquid phase immobilized by a three-dimensional network composed of self-assembled, crosslinked or entangled gelator fibers. Organogel applications are various, including chemistry, pharmaceuticals, cosmetics, biotechnologies and food technology. In pharmacology, they are used as drug and vaccine delivery platforms for active ingredients via diverse routes such as transdermal, oral and parenteral. In a close past, their uses as drug delivery systems have been unfortunately hampered by the toxicity of the selected organic solvents. More recently, the synthesis of more biocompatible organogels has strengthened the development of several biomedical and pharmaceutical applications. This review provides a global view of organogels, such as nature, syntheses, characterizations and properties. An emphasis is placed on the most recent technologies used in the design of organogels as potential controlled delivery systems. A particular attention is provided to their newest therapeutic applications.

The development of in vitro embryo production (IVEP) techniques in Felis catus is a fitting model with potential application to the conservation of endangered felid species. To improve the quality of IVEP techniques an appropriate balance of pro- and antioxidants should be provided. Under in vitro conditions, high levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) mRNA provide a defence mechanism against oxidative stress for embryos. In order to improve the development of cat oocytes, the effects of SOD and CAT supplemented to in vitro maturation (IVM) medium and of GPx supplemented to in vitro fertilization (IVF) medium on development and embryo production in vitro were evaluated. Data showed an increase of 70 and 77 % of cleaved embryo and blastocyst formation, respectively, in the experiment with SOD and CAT addition to IVM medium; in the experiment with GPx addition to IVF medium the number of cleaved embryos doubled and the number of embryos increased by 96 %. Therefore, our results were positive and encourage us to continue studies on cat oocytes evaluating the effects of various dosages and combination of antioxidants.

Background and aims Scavenger receptor class B member 3, also known as cluster of differentiation-36 (CD36) receptor, is involved in the uptake and accumulation of modified lipoprotein in macrophages, driving atherosclerosis progression. Azapeptide analogs of growth hormone-releasing peptide-6 (GHRP-6) have been developed as selective CD36 ligands and evaluated for their anti-atherosclerotic properties in apoe−/− mice. Methods From 4 to 19 weeks of age, male apoe−/− mice were fed a high fat high cholesterol (HFHC) diet, then switched to normal chow and treated daily with 300 nmol/kg of MPE-001 ([aza-Tyr4]-GHRP-6) or MPE-003 ([aza-(N,N-diallylaminobut-2-ynyl)Gly4]-GHRP-6) for 9 weeks. In another protocol, mice were fed a HFHC diet throughout the study. Results Azapeptides decreased lesion progression in the aortic arch and reduced aortic sinus lesion areas below pre-existing lesions levels in apoe−/− mice which were switched to chow diet. In mice fed a HFHC throughout the study, azapeptides reduced lesion progression in the aortic vessel and sinus. The anti-atherosclerotic effect of azapeptides was associated with a reduced ratio of iNOS+/CD206+ macrophages within lesions, and lowered plasma inflammatory cytokine levels. Monocytes from azapeptide-treated mice showed altered mitochondrial oxygen consumption rates, consistent with an M2-like phenotype. These effects were dependent on CD36, and not observed in apoe−/−cd36−/− mice. Conclusions Azapeptides MPE-001 and MPE-003 diminished aortic lesion progression and reduced, below pre-existing levels, lesions in the aortic sinus of atherosclerotic mice. A relative increase of M2-like macrophages was observed in lesions, associated with reduced systemic inflammation. Development of CD36-selective azapeptide ligands merits consideration for treating atherosclerotic disease.

Most bioactive food components show a rapid inactivation or biodegradation that challenge their beneficial effects. Since regulation authorities require efficient food quality and acceptability, edible passive coating has been developed to improve and extend food shelf life while protecting nutritional values. Encapsulation processes in oil and fat structures therefore provide a high protection for fat soluble nutraceuticals, as sustained and controlled delivery systems. Among the various existing systems, nanoorganogels offer unique properties due to their multiplied surface, while preserving the physical properties of bulk materials. Thus, nanoencapsulation currently receives a lot of attention from industrial R&Ds. Screening approaches have been developed to promote food-grade and GRAS-approved organogelators available for the scaled up manufacture of nanoscale organogel delivery systems. Ongoing challenges of the food industry include intensifying the search for viable health-promoting nanomaterials or nanostructured matrices displaying desirable properties in food applications. In these aspects, the nanoorganogel technologies have recently shown tremendous potential in food applications as structured edible oils, dietary supplements with high oral bioavailability or safer preservative agents for consumers.

International audience; Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non– HLA-sensitized patients who had received an ABOcompatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p < 0.0001). AMR occurred more often in the transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation butnot for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients.

Reconstruction after excision of infiltrating basal cell carcinomas (BCCs) of the upper pole of the ear can be achieved with different techniques. The concept of spare-part surgery, which allows the surgeon to perform primary reconstruction of a defect without harvesting tissue from the adjacent areas, has been applied to the ear anatomy. We describe our experience with the use of a fillet flap from the residual external ear in two patients out of a series of six, undergoing reconstruction of ear defects after infiltrating BCC resection between January 2011 and December 2014. Reconstruction with the fillet of pinna flap was proven to be an easy surgical technique with good functional and cosmetic outcomes. Our technique, not previously reported, enhances the versatility of ear reconstruction.

Organogels prepared with low molecular weight organogelators to structure liquid oils represent excellent matrices for the controlled delivery of a wide variety of drug molecules. Although studies on organogel systems are reported in the literature, relatively few investigate their potential as gels formed in situ intended for drug delivery. This study reports the development of injectable subcutaneous 12- hydroxystearic acid (12-HSA) organogels for the delivery of both lipophilic and hydrophilic drugs. The rheological characterization (flow, dynamic temperature ramp and amplitude oscillatory measurements) and physicochemical properties (syringeability, swelling and degradation studies), as well as permeability and cytotoxicity were analyzed to gain insights into the influence of the gel composition (surfactant addition, organogelator concentration) on the gelation process and organogel properties. Sol-gel phase transition temperature (Tgel) and gel-sol phase transition temperature (Tmelt) were determined by the tube-inverting method and complementary rheology studies. An increase in 12-HSA concentration led to an augmentation in gel strength and storage (G′) and loss (G″) moduli values, evidencing the self-assembly of crystalline gelator structure entrapping the oil phase into a three-dimensional (3D) network. The addition of polysorbate 80 (Tween 80, T80) surfactant molecules in the system caused a weaker gel-like structure, with lower flow rate during syringeability assays, despite its lower apparent viscosity compared to those of 12-HSA organogels. In addition, the swelling studies of 12-HSA/12-HSA T80 organogels as a function of time in phosphate buffered saline (PBS) revealed that the erosion rates were modulated by the organogel compositions. The permeability of acyclovir (ACV) and clotrimazole (CTM), hydrophilic and lipophilic model drugs, respectively, loaded in 12-HSA-based organogels, was assessed in Franz diffusion cells. Organogel-loaded drugs presented lower in vitro release rates and ex vivo drug permeabilities compared to the corresponding drug solutions. Furthermore, 12-HSA T80 organogel could slow down the release of ACV by a factor of about 2.6-fold, up to 6 h, compared to CTM-loaded 12-HSA organogels. Finally, the cytotoxicity of 12-HSA-based organogels was evaluated through in vitro cell viability assays in human foreskin fibroblasts (HFF). Increased 12-HSA concentration resulted in higher cytotoxic effect, with a higher test sensitivity observed for the 3D collagen-embedded cell layer setup matrix versus 2-D cell cultures. Our results support the hypothesis that 12-HSA-based organogels are promising systems for controlled drug delivery as in situ-forming implants.

Bottled water consumption has a long history but nowdays bottled water industry is a fast-growing sector of the world industry. Most of the water in bottles comes from springs or underground aquifers. The mineral content of the aquifer is diluted in small amounts into the water and although consuming mineral water is thought to be a healthy practice, there are several cases where radioactivity is also present. Monitoring the bottled water natural radioactivity is very important especially for the cases people consume mainly this kind of water. Radioactivity accumulation in the human body if exists in excess, can pose a threat for the health. In the present work, thirty brands of Italian bottled water were measured for gross alpha and beta radioactivity, uranium, radium and polonium radioisotopes. Radioactivity content was determined using the LSC method and sorbtion on polyamide pieces covered with thin film of MnO 2 . The analysis using the MnO 2 thin films showed that the radium activity in waters varied from 4.7-69.3 mBqL -1 and the polonium activity varied from 5.9-26.8 mBqL -1 . The measurements with the LSC method showed uranium concentrations varying from 0.7- 93.1 mBqL -1 , while the radium activities exhibited variations from 1.6-34.1 mBqL -1 . Finally the gross beta activity values varied from 13.1-1584.9 mBqL -1 and the gross alpha from 2.4- 305.2 mBqL -1 .

ISIS recruits from Western societies have triggered a global emphasis on countering violent extremism. This chapter will address the connection between Islamophobia and radicalization: the cultural construction of Islamophobic discourse, role of media and social media on Islamophobia and radicalization, legitimacy of purported theological roots and their impact on domestic and foreign policies.

An important prophetic tradition maintains that “Islam was built upon five ‘foundations.’ ” The Five Pillars (the profession of faith [shahadah], daily prayers [salat], almsgiving [zakat], the fast of Ramadan [sawm], and the pilgrimage to Mecca [Hajj])...

Criticisms of Islam and Islamic law often focus on reports and media coverage of harsh hudud punishments in Muslim countries. This chapter compares the rationales and goals of Islamic criminal laws in their original context with hudud punishments in the post-colonial period. The original rigorous...

Muslim countries and societies face major human rights challenges today, especially for those living under patriarchal societies and authoritarian rule. These include equal rights for women; freedom of religion, speech, and expression; and freedom of the press. Major polls report that majorities of Muslims strongly...

Shariah: What Everyone Needs to Know provides informed answers to many questions and charges that surround the debate over Shariah and Islamic Law. As its title indicates, we have written for a broad nonspecialist audience as well as for policymakers, political commentators, religious leaders,...