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Competing Interests: All authors declare no conflict of interest.

Background: Gestational diabetes mellitus (GDM) has been rising in the United States, and it poses significant health risks to pregnant individuals and their infants. Prior research has shown that individuals with GDM also experience prevalent stress and mental health issues, which can further contribute to glucose regulation difficulties. Stigma associated with GDM may contribute to these mental health challenges, yet there is a lack of focused research on GDM-related stigma, its impact on psychological health, and effective coping mechanisms. Thus, this qualitative study aims to understand individuals' experiences related to GDM stigma, mental health, and facilitative coping., Methods: In-depth, semi-structured interviews were conducted with 14 individuals with a current or recent (within the last year) diagnosis of GDM. Thematic analysis was employed to guide data analysis., Results: Four themes emerged from data analysis: (1) experience of distal GDM stigma including stigmatizing provider interactions, stigma from non-medical spaces, and intersecting stigma with weight, (2) internalized GDM stigma, such as shame, guilt, and self-blame, (3) psychological distress, which included experiences of stress and overwhelm, excessive worry and fear, and loneliness and isolation, and (4) facilitative coping mechanisms, which included diagnosis acceptance, internet-based GDM community, active participation in GDM management, social and familial support, and time for oneself., Conclusions: Findings demonstrate the relevance of GDM stigma in mental health among people with GDM and the need for addressing GDM stigma and psychological health in this population. Interventions that can reduce GDM stigma, improve psychological wellness, and enhance positive coping may facilitate successful GDM management and healthy birth outcomes. Future quantitative, theory-driven research is needed to understand the prevalence of GDM stigma experiences and mechanisms identified in the current study, as well as among marginalized populations (e.g., individuals of color, sexual and gender minorities)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Esophageal thermal injury is a complication of atrial fibrillation (AF) ablation, and it can be avoided by esophageal deviation during left atrial posterior wall radiofrequency catheter ablation., Objective: This study aimed to evaluate the safety of a nitinol-based mechanical esophageal displacement device (MEDD) and its performance., Methods: This preclinical safety study was conducted on 20 pigs, with 10 undergoing radiofrequency AF ablation using the MEDD and 10 serving as a control group under anticoagulation but without radiofrequency application. Esophageal traumatic injuries were classified from 0 to 4 and were grouped as absent (grade 0), minor (grade 1 or 2), moderate (grade 3), or major risk lesions (grade 4) by anatomopathological study. Grades 1 and 2 were considered acceptable. Fluoroscopy was used to measure displacement., Results: Five (25%) pigs developed traumatic lesions, 4 with grade 1 and 1 with grade 2 (2-mm superficial ulcer). There was no difference in lesion occurrence between the radiofrequency and control groups (30% and 20%, respectively; P = .43). Under rightward displacement, the right edge moved 23.9 (interquartile range [IQR] 21.3-26.3) mm and the left edge moved 16.3 (IQR 13.8-18.4) mm ( P < .001) from baseline. Under leftward displacement, the right edge moved 13.5 (IQR 10.9-15.3) mm and the left edge moved 16.5 (IQR 12.3-18.5) mm ( P = .07). A perforation to the pharyngeal diverticulum occurred in 1 pig, related to an accidental extubation., Conclusion: In pigs, the MEDD demonstrated safety in relation to esophageal tissue, and successful deviation. Esophageal traumatic injuries were acceptable, but improper manipulation led to pharyngeal lesion., (© 2023 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Background: Functional bradycardia is a challenging condition that affects a healthy population. Ganglionated plexus ablation has emerged as a therapeutic alternative to avoid a pacemaker., Objectives: The purpose of this study is to evaluate long-term effects of anatomically guided cardiac denervation., Methods: This is a prospective longitudinal study that included 36 patients with symptomatic functional bradycardia. Electroanatomic reconstruction of both atria was carried out, and the main septal ganglionated plexi were anatomically located and targeted., Results: Ablation endpoints were: 1) heart rate increment; 2) Wenckebach cycle length shortening; and 3) atrio-Hisian (AH) interval shortening. A sinus node denervation was obtained in all patients with an increment of 21.6% in the mean heart rate. All patients presented a negative atropine test after ablation. Twenty-eight (77.7%) patients presented immediate sings of atrioventricular node denervation, with a shortening of 15.6% of mean Wenckebach cycle length and 15.9% of the mean AH interval. All heart rate variability parameters showed a significant reduction after 12 months, enduring after 18 months. Thirty (83.3%) patients remained free of events after a mean follow-up of 52.1 ± 35.2 months. One patient (2.77%) presented acute sinus node artery occlusion during ablation with persistent sinus dysfunction and had a pacemaker implantation; 3 (8.3%) other patients evolved with sinus tachycardia, and 4 (11.1%) patients presented syncope recurrence during follow-up, 3 (8.3%) of them requiring a pacemaker implantation. No other tachyarrhythmia was observed., Conclusions: The anatomically guided septal approach is an effective technique for syncope prevention, promoting long-lasting autonomic changes. No significant proarrhythmia effect has been observed during the long-term follow-up., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices., Materials and Methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization)., Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice., Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

Inertia is a measure of a power system's capability to counteract frequency disturbances: in conventional power networks, inertia is approximately constant over time, which contributes to network stability. However, as the share of renewable energy sources increases, the inertia associated to synchronous generators declines, which may pose a threat to the overall stability. Reliably estimating the inertia of power systems dominated by inverted-connected sources has therefore become of paramount importance. We develop a framework for the continuous estimation of the inertia in an electric power system, exploiting state-of-the-art artificial intelligence techniques. We perform an in-depth investigation based on power spectra analysis and input-output correlations to explain how the artificial neural network operates in this specific realm, thus shedding light on the input features necessary for proper neural-network training. We validate our approach on a heterogeneous power network comprising synchronous generators, static compensators and converter-interfaced generation: our results highlight how different devices are characterized by distinct spectral footprints - a feature that must be taken into account by transmission system operators when performing online network stability analyses., (© 2023. The Author(s).)

Introduction: Originally regarded as garnish greens, microgreens are increasingly valued for their nutritional profile, including their mineral content., Methods: A study was conducted under controlled environmental conditions utilizing a selection of seventeen microgreen species belonging to seven different botanical families to investigate the genetic variation of macro- and micro-minerals and nitrate (NO 3 - ) content. Plants were grown in a soilless system using a natural fiber mat as the substrate. After germination, microgreens were fertigated with a modified half-strength Hoagland solution prepared using deionized water and without adding microelements. At harvest (10 to 19 days after sowing, based on the species), yield components were measured and dry tissue samples were analyzed for the concentration of total nitrogen (N), NO 3 - , P, K, Ca, Mg, S, Na, Fe, Zn, Mn, Cu, and B., Results and Discussion: Genotypic variations were observed for all of the examined parameters. Nitrogen and K were the principal macronutrients accounting for 38.4% and 33.8% of the total macro-minerals concentration, respectively, followed in order by Ca, P, S, and Mg. Except for sunflower ( Helianthus annuus L.), all the tested species accumulated high (1,000-2,500 mg kg -1 FW) or very high (>2,500 mg kg -1 FW) NO 3 - levels. Eight of the studied species had a K concentration above 300 mg 100 g -1 FW and could be considered as a good dietary source of K. On the other hand, scallion ( Allium fistulosum L.), red cabbage ( Brassica oleracea L. var. capitata ), amaranth ( Amaranthus tricolor L.), and Genovese basil ( Ocinum basilicum L.) microgreens were a good source of Ca. Among micro-minerals, the most abundant was Fe followed by Zn, Mn, B, and Cu. Sunflower, scallion, and shiso ( Perilla frutescens (L.) Britton) were a good source of Cu. Moreover, sunflower was a good source of Zn, whereas none of the other species examined could be considered a good source of Fe and Zn, suggesting that supplementary fertilization may be required to biofortify microgreens with essential microminerals. In conclusion, the tested microgreens can be a good source of minerals showing a high potential to address different dietary needs; however, their yield potential and mineral profile are largely determined by the genotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Gioia, Hong, Pisani, Petropoulos, Bai and Rosskopf.)

The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma membrane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare inherited disease, causes ventricular tachycardia, sudden cardiac death, and heart failure (HF). We investigated ARVC clinical features, genetic findings, natural history, and the occurrence of life-threatening arrhythmic events (LTAEs), HF death, or heart transplantation (HF-death/HTx) to identify risk factors., Methods: The clinical course of 111 consecutive patients with definite ARVC, predictors of LTAE, HF-death/HTx, and combined events were analyzed in the entire cohort and in a subgroup of 40 patients without sustained ventricular arrhythmia before diagnosis., Results: The 5-year cumulative probability of LTAE was 30% and HF-death/HTx was 10%. Predictors of HF-death/HTx were reduced right ventricle ejection fraction (HR: 0.93; P =0.010), HF symptoms (HR: 4.37; P =0.010), epsilon wave (HR: 4.99; P =0.015), and number of leads with low QRS voltage (HR: 1.28; P =0.001). Each additional lead with low QRS voltage increased the risk of HF-death/HTx by 28%. Predictors of LTAE were prior syncope (HR: 1.81; P =0.040), number of leads with T wave inversion (HR: 1.17; P =0.039), low QRS voltage (HR: 1.12; P =0.021), younger age (HR: 0.97; P =0.006), and prior ventricular arrhythmia/ventricular fibrillation (HR: 2.45; P =0.012). Each additional lead with low QRS voltage increased the risk of LTAE by 17%. In patients without ventricular arrhythmia before clinical diagnosis of ARVC, the number of leads with low QRS voltage (HR: 1.68; P =0.023) was independently associated with HF-death/HTx., Conclusions: Our study demonstrated the characteristics of a specific cohort with a high prevalence of arrhythmic burden at presentation, male predominance, younger age and HF severe outcomes. Our main results suggest that the presence and extension of low QRS voltage can be a risk predictor for HF-death/HTx in ARVC patients, regardless of the arrhythmic risk. This study can contribute to the global ARVC risk stratification, adding new insights to the international current scientific knowledge.

Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F 2 -Isoprostanes (F 2 -IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F 2 -IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-Müllerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions.

Carya&nbsp;illinoinensis (Wangenh.) K.Koch production has expanded beyond the native distribution as the genetic diversity of the species, in part, has allowed the trees to grow under broad geographic and climatic ranges. Research in other plant species has demonstrated that the phytobiome enhances their ability to survive and thrive in specific environments and, conversely, is influenced by the prevailing environment and plant genetics, among other factors. We sought to analyze the microbiota of pecan seedlings from the controlled cross 'Lakota' × 'Oaxaca' that were made in Georgia and Texas, respectively, to determine if the maternal geographical origin influences the microbiome of the resulting progeny. No significant differences in bacterial communities were observed between the seeds obtained from the two different states ( p = 0.081). However, seed origin did induce significant differences in leaf fungal composition ( p = 0.012). Results suggest that, in addition to some environmental, epigenetics, or host genetic components, ecological processes, such as dispersal mechanisms of the host, differentially impact the pecan microbiome, which may have ramifications for the health of trees grown in different environments. Future studies on the role of the microbiome in plant health and productivity will aid in the development of sustainable agriculture for improved food security.

Background: Direct comparisons of combined (C-ABL) and non-combined (NC-ABL) endo-epicardial ventricular tachycardia (VT) ablation outcomes are scarce. We aimed to investigate the long-term clinical efficacy and safety of these 2 strategies in ischemic heart disease (IHD) and non-ischemic cardiomyopathy (NICM) populations., Methods: Multicentric observational registry included 316 consecutive patients who underwent catheter ablation for drug-resistant VT between January 2008 and July 2019. Primary and secondary efficacy endpoints were defined as VT-free survival and all-cause death after ablation. Safety outcomes were defined by 30-day mortality and procedure-related complications., Results: Most of the patients were male (85%), with IHD (67%) and mean age of 63 ± 13 years. During a mean follow-up of 3 ± 2 years, 117 (37%) patients had VT recurrence and 73 (23%) died. Multivariate survival analysis identified electrical storm (ES) at presentation, IHD, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class III / IV, and C-ABL as independent predictors of VT recurrence. In 135 patients undergoing repeated procedures, only C-ABL and ES were independent predictors of relapse. The identified independent predictors of mortality were C-ABL, ES, LVEF, age, and NYHA class III / IV. C-ABL survival benefit was only seen in patients with a previous ablation (P for interaction = 0.04). Mortality at 30 days was similar between NC-ABL and C-ABL (4% vs. 2%, respectively, P = 0.777), as was complication rate (10.3% vs. 15.1%, respectively, P = 0.336)., Conclusion: A combined or sequential endo-epicardial VT ablation strategy was associated with lower VT recurrence and lower all-cause death in IHD and NICM patients undergoing repeated procedures. Both approaches seemed equally safe., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to analyze variation in body mass index (BMI) and skeletal muscle index (SMI) in head and neck squamous cell carcinoma (HNSCC) patients who underwent exclusive radiotherapy (RT) or concurrent chemo-radiotherapy (RT-CHT). We enrolled 73 HNSCC pts treated with definitive or post-operative RT (14 pts) or RT-CHT (59 pts). At the time of diagnosis (t0) and 3 months after treatment completion (t3), CT scans were retrieved to measure skeletal muscle at the level of the C3 vertebra. Median follow-up was 16 months. Nine disease progressions with distant metastases and eleven local relapses were observed. Fifty-three pts were free from progression at 1 year. At t0, average BMI was 25.8 (SD 4.1), while at t3 it was 24.5, with no reduction in 54 pts. A BMI decrease of −1.3 (p-value < 0.0001) between t0 and t3 was found with the Wilcoxon signed-rank test. SMI was 57.1 and 59.2 at t0 and t3, respectively (p-value = 0.005). According to our analysis, SMI variation seems to reflect the effect of an appropriate nutritional intervention and may represent a reliable, simple tool for muscle mass analysis.

Nearest neighbor spatial interpolation for mapping continuous populations and finite populations of areas or units is approached from a design-based perspective, that is, populations are fixed, and uncertainty stems from the sampling scheme adopted to select locations. We derive conditions for design-based pointwise and uniform consistency of the nearest neighbor interpolators. We prove that consistency holds under certain schemes that are widely applied in environmental and forest surveys. Furthermore, we propose a pseudopopulation bootstrap estimator of the root mean squared errors of the interpolated values. Finally, a simulation study is performed to assess the theoretical results., (© 2021 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Background: In the treatment of atrial fibrillation (AF), the most frequently sustained arrhythmia, with catheter ablation (CA) or electrical cardioversion (ECV), the periprocedural period is one of the most critical phases. Currently, the use of new direct action oral anticoagulants (DOAC) is increasingly frequent; however, in the real world, there are still few data on studies on the thrombus incidence in the left atrium (TrLA) or dense spontaneous contrast (DSC) on transesophageal echocardiogram (TEE)., Objective: To evaluate the prevalence of events and association with risk factors in patients using DOACs. Primary objective: to analyze the prevalence of thrombus in the LA by TEE in patients using DOAC undergoing ECV/CA. Second, evaluate the association of comorbidities with the presence of thrombi and DSC., Methods: Retrospective cohort, single-center study with patients followed at the Arrhythmia Outpatient Unit (InCor-HCFMUSP). Patients indicated for procedures and using DOACs were selected, and their clinical/echocardiographic data were analyzed. A significance level of 5% was considered., Results: 354 patients were included, a total of 400 procedures, from March 2012-March 2018. Thrombus in the LA was found in 11 patients (2.8%), associated with advanced age (p=0.007) and higher CHA2DS2-VASc (p&lt;0.001) score. DSC in the LA before TEE was found in 29 patients (7.3%), with lower LVEF (p&lt;0.038) and greater LA dimension (p&lt;0.0001)., Conclusion: The incidence of LA thrombus and DSC in patients using DOC in the context of AF ECV/CA, although small, is not negligible. Patients with higher CHA2DS2-VASc scores, especially older and with larger LA diameter, are more prone to these echocardiographic findings.

Cardioneural ablation is a novel treatment for functional bradycardia. However, the risk of acute complications is still unknown. The aim of this case report is to describe acute occlusion of the sinus node artery after cardiac denervation procedures in 2 patients and to encourage measures to prevent it, such as evaluating the aortic angulation in older patients before the procedure and by monitoring signs of sinus failure during ablation in patients with electroanatomical maps showing a constricted aspect of the right atrium. ( Level of Difficulty: Advanced. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

This work presents, for the first time, a detailed report on how the nucleation and crystallization of polylactide (PLLA) are affected by biobased aliphatic polyesters plasticizers. Three biobased polyesters were synthesized via solvent-free two-stage melt polycondensation of adipic acid (AdA) with three different biobased aliphatic diols and used as plasticizers for poly (L-lactic acid) (PLLA). The molecular structure of the synthesized polyesters was proved using 1 H NMR, 13 C NMR and Fourier transform infrared (FTIR) spectroscopy. PLLA/AdA-based blends containing 10 wt% of the polyester plasticizers were studied by tensile tests, dynamic mechanical analysis (DMA), wide-angle x-ray scattering (WAXS), differential scanning calorimetry (DSC) and polarized light optical microscopy (PLOM). Adding the plasticizers to PLLA decreased T g by up to 11 °C and significantly increased the elongation at break by about 8 times compared with neat PLLA. The addition of 10 wt% of any AdA-based plasticizer to PLLA increases the nucleation rate from the glassy state by around 50-110 % depending on the plasticizer. The overall crystallization rate from the glassy state was 2-3 times faster for the plasticized PLLAs than neat PLLA. These results are a consequence of the lower energy barrier for both nucleation and growth processes. The incorporation of AdA-based linear polyesters had an incremental impact on the crystal growth rate (or secondary nucleation) of PLLA spherulites from the melt and glassy states. In conclusion, the AdA-based aliphatic polyesters allowed to enhance PLLA crystallization rates and showed interesting potential for the formulation of fully biobased PLLA blends., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim and Background: The present study aims to identify predictive factors for urinary toxicity and self-reported symptoms after external beam radiotherapy (EBRT) for prostate cancer., Methods: Two-hundred and eighty patients treated with EBRT for prostate cancer were included in the present study. Toxicity was scored following the grading system based on Radiation Therapy Oncology Group (RTOG) scale. International Prostatic Symptom Score (IPSS) and Consultation on Incontinence Questionnaires - Short Form (ICIQ-SF) were used to analyse self-reported symptoms. Acute and late urinary toxicities were correlated to clinical and treatment parameters, radiation dosimetry data, IPSS and ICIQ-SF., Results: Median patient age was 74 years (range, 64-83). Thirty-one percent experienced acute G1 urinary toxicity, 24% G2 and 3% G3. Fourteen percent experienced G1 late urinary toxicity and 3% G2. Bladder volume<200 cc was associated with acute urinary toxicity (P=0.014); use of MRI for treatment planning allowed a lower incidence of late toxicity (P=0.062) and use of IMRT allowed for reduced incidence in late toxicity (P=0.038). Maximum bladder dose correlated with late urinary toxicity (P=0.014). The analysis of self-reported symptoms showed a significant correlation between IPSS baseline values (P=0.009), presence of nocturia (P=0.002), bladder urgency (P=0.024) and incontinence (P=0.024) and development of acute urinary toxicity at univariate analysis. At multivariate logistic regression analysis, bladder filling, IPSS value, nocturia, and urinary incontinence retained significant correlation with acute toxicity (P=0.0003)., Discussion: Significant independent predictors for acute urinary toxicity grade≥2 were bladder filling, IPSS value, nocturia, and urinary incontinence at baseline assessment., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Aim: To describe a simple and useful technique for acute management of massive hemopericardium inside the Electrophysiology (EP) laboratory METHODS AND RESULTS: Five patients from a single center experience were identified, all with blood loss above 1000 ml after initial pericardiocenthesis. Using two long 8.5 F transseptal sheaths inside the pericardium space, with continuous negative pressure, allowed the complete cessation of bleeding or hemodynamic maintenance until definitive surgical repair in all patients CONCLUSION: The use of two long sheaths for blood drainage, instead of conventional pericardiocenthesis, might be helpful to manage massive hemopericardium inside EP lab, avoiding urgent cardiac surgery or maintaining clinical stability until surgical staff is available., (© 2022 Wiley Periodicals LLC.)

Soilborne pests are a major obstacle that must be overcome for the production of horticultural crops. Methyl bromide (MBr) was an effective preplanting soil broad-spectrum biocide, but its use has been banned due to its role in depleting the ozone layer. As a result, sustainable alternative methods for controlling soilborne pathogens and pests are needed. Nitrous oxide (N 2 O) emissions are of concern in crop production due to the role of N 2 O as a greenhouse gas. Agricultural lands are known sources for emission of N 2 O into the atmosphere. Emissions are related to many environmental factors as well as fertilization and fumigation practices. This study evaluated the influence of different alternatives to MBr on N 2 O emissions throughout a tomato production season in two locations representative of southern and northern Florida. We evaluated eight soil management practices, including (a) untreated controls; (b) chemical soil fumigation; (c) anaerobic soil disinfestation using molasses (M) + composted poultry litter and (d and e) M + composted yard waste (CYW, at two rates); (f) Soil Symphony Amendment (SSA), a commercially available mix of microbes and nutrients; (g) CYW alone; and (h) CYW + SSA. Nitrous oxide emissions were measured throughout the cropping season. Emissions were highest on the day of planting (Day 21), ranging from 213 to 1,878 μg m -2 h -1 , likely due to the release of N 2 O that had accumulated under the totally impermeable film when it was punctured for planting. However, statistical significance varied between sites. Estimated cumulative emissions of N 2 O throughout the production season ranged from 1.3 to 4.8 kg N 2 O-N ha -1 ., (© 2022 The Authors. Journal of Environmental Quality © 2022 American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Normal tissue radiosensitivity is thought to be influenced by an individual's genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2-3 subcutaneous fibrosis and/or grade 2-3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance ( p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82-2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51-14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06-3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence.

Ayurveda is a system of holistic medicine that integrates health with lifestyle to restore balance and remove disease by resolving the imbalance that causes it. Ayurvedic techniques that support digestion, immunity, vitality, and rejuvenation can help assist women with a healthy conception, pregnancy, delivery, and postpartum. Ayurvedic approaches can help common but bothersome pregnancy symptoms as well as potentially prevent more serious pregnancy complications. Specific techniques, including developing a daily routine and the practice of pranayama to support vitality through breathing exercises are described to help guide modern obstetrical practice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Genome-enabled biotechnologies have the potential to accelerate breeding efforts in long-lived perennial crop species. Despite the transformative potential of molecular tools in pecan and other outcrossing tree species, highly heterozygous genomes, significant presence-absence gene content variation, and histories of interspecific hybridization have constrained breeding efforts. To overcome these challenges, here, we present diploid genome assemblies and annotations of four outbred pecan genotypes, including a PacBio HiFi chromosome-scale assembly of both haplotypes of the 'Pawnee' cultivar. Comparative analysis and pan-genome integration reveal substantial and likely adaptive interspecific genomic introgressions, including an over-retained haplotype introgressed from bitternut hickory into pecan breeding pedigrees. Further, by leveraging our pan-genome presence-absence and functional annotation database among genomes and within the two outbred haplotypes of the 'Lakota' genome, we identify candidate genes for pest and pathogen resistance. Combined, these analyses and resources highlight significant progress towards functional and quantitative genomics in highly diverse and outbred crops.

Summary: How do we stand facing silence, as human beings before therapists? A look at the silence in music and in the therapeutic field to focus attention to silence as tool for Music Therapy. In Latin Language we have two words to define silence, tacere and silere and the nuances between their meanings arise clearly; recognize them in our daily life and in the therapeutic relationship can be a source to achieve an authentic listening and a greater awareness of the time of return to the sound gesture. Moreover, looking for pauses in therapeutic listening, open to stimulating field of research on the bodily effects caused not only by the peculiarities of the musical (melody, harmony, rhythm, timbre), but also by the different balances between sound and silence., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by GIMLE.)

Background: Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT)., Methods: Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples., Discussion: This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies., Trial Registration: ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 - retrospectively registered.

Aims: To develop quality indicators (QIs) that may be used to evaluate the quality of care and outcomes for adults with atrial fibrillation (AF)., Methods and Results: We followed the ESC methodology for QI development. This methodology involved (i) the identification of the domains of AF care for the diagnosis and management of AF (by a group of experts including members of the ESC Clinical Practice Guidelines Task Force for AF); (ii) the construction of candidate QIs (including a systematic review of the literature); and (iii) the selection of the final set of QIs (using a modified Delphi method). Six domains of care for the diagnosis and management of AF were identified: (i) Patient assessment (baseline and follow-up), (ii) Anticoagulation therapy, (iii) Rate control strategy, (iv) Rhythm control strategy, (v) Risk factor management, and (vi) Outcomes measures, including patient-reported outcome measures (PROMs). In total, 17 main and 17 secondary QIs, which covered all six domains of care for the diagnosis and management of AF, were selected. The outcome domain included measures on the consequences and treatment of AF, as well as PROMs., Conclusion: This document defines six domains of AF care (patient assessment, anticoagulation, rate control, rhythm control, risk factor management, and outcomes), and provides 17 main and 17 secondary QIs for the diagnosis and management of AF. It is anticipated that implementation of these QIs will improve the quality of AF care., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

CCHCR1 (Coiled-Coil alpha-Helical Rod 1), maps to chromosomal region 6p21.3, within the major psoriasis susceptibility locus PSORS1. CCHCR1 itself is a plausible psoriasis candidate gene, however its role in psoriasis pathogenesis remains unclear. We previously demonstrated that CCHCR1 protein acts as a cytoplasmic docking site for RNA polymerase II core subunit 3 (RPB3) in cycling cells, suggesting a role for CCHCR1 in vesicular trafficking between cellular compartments. Here, we report a novel interaction between CCHCR1 and the RNA binding protein HAX1. HAX1 maps to chromosomal region 1q21.3 within the PSORS4 locus and is over-expressed in psoriasis. Both CCHCR1 and HAX1 share subcellular co-localization with mitochondria, nuclei and cytoplasmic vesicles as P-bodies. By a series of ribonucleoprotein immunoprecipitation (RIP) assays, we isolated a pool of mRNAs complexed with HAX1 and/or CCHCR1 proteins. Among the mRNAs complexed with both CCHCR1 and HAX1 proteins, there are Vimentin mRNA, previously described to be bound by HAX1, and CAMP/LL37 mRNA, whose gene product is over-expressed in psoriasis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To perform a clinical audit to assess adherence to standard clinical practice for the diagnosis, treatment, and follow-up of patients undergoing radiotherapy for rectal cancer treatment in four European countries., Materials and Methods: Multi-institutional, retrospective cohort study of 221 patients treated for rectal cancer in 2015 at six European cancer centres. Clinical indicators applicable to general radiotherapy processes were evaluated. All data were obtained from electronic medical records., Results: The audits were performed in the year 2017. We found substantial inter-centre variability in adherence to standard clinical practices: 1) presentation of cases at departmental clinical sessions (range, 0-100%) or multidisciplinary tumour board (50-95%); 2) pretreatment MRI (61.5-100%) and thoracoabdominal CT (15.0-100%). Large inter-centre differences were observed in the mean interval between biopsy and first visit to the radiotherapy department (range, 21.6-58.6 days) and between the first visit and start of treatment (15.1-38.8 days). Treatment interruptions ≥ 1 day occurred in 43.9% (2.5-90%) of cases overall. Treatment compensation was performed in 2.1% of cases. Treatment was completed in the prescribed time in 55.7% of cases., Conclusions: This multi-institutional clinical audit revealed that most centres adhered to standard clinical practices for most of the radiotherapy processes-related variables assessed. However, the audit revealed marked inter-centre variability for certain quality indicators, particularly inconsistent record keeping. Multiple targets for improvement and/or harmonisation were identified, confirming the value of routine clinical audits to detect potential deviations from standard clinical practice.

The loss of methyl bromide as a soil fumigant and minimal advances in the development and registration of new chemical fumigants has resulted in a resurgence of interest in the application of organic amendments (OAs) for soilborne plant pathogen and plant-parasitic nematode management. Significant progress has been made in the characterization of OAs, application of strategies for their use, and elucidation of mechanisms by which they suppress soilborne pests. Nonetheless, their utility is limited by the variability of disease control, expense, and the logistics of introducing them into crop production systems. Recent advances in molecular techniques have led to significant progress in the elucidation of the role of bacteria and fungi and their metabolic products on disease suppression with the addition of OAs. Biosolarization and anaerobic soil disinfestation, developed to manipulate systems and favor beneficial microorganisms to maximize their impact on plant pathogens, are built on a strong historical research foundation in OAs and the physical, chemical, and biological characteristics of disease-suppressive soils. This review focuses on recent applications of OAs and their potential for the management of soilborne plant pathogens and plant-parasitic nematodes, with emphasis primarily on annual fruit and vegetable production systems.

Purpose: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual)., Methods: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning., Results: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D 15% and D mean were reduced by 8.1% and 17.9%, bladder D 25% and D mean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable., Conclusion: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

On January 30, 2020, World Health Organization (WHO) stated that a new coronavirus disease outbreak [COronaVIrus Disease - 19 (COVID-19)] was an international public health emergency. Many news, often fake ones, about the derived pandemic rapidly spread along the media, thus leading many dermatological patients to identify as "risk category" and sometimes discontinue treatments by themselves. The Dermatology Units in Grosseto and Pordenone simultaneously carried out a data collection by remote-conducted visits, evaluating the incidence of COVID-19 in psoriatic patients. Only 1 patient (close contact of a case) as part of the psoriasis analyzed group was tested and turned out to be positive for SARS-CoV-2, developing no symptoms during the observation period. The collected information may suggest that psoriasis, biotechnologically treated or not, cannot promote or aggravate the clinical trend of the SARS-CoV-2 infection, hence stopping systemic therapy in negative or clinically free SARS-CoV-2 patients is not recommended in general., Competing Interests: Conflict of interests: The Authors declare no potential conflict of interests., (©Copyright: the Author(s).)

Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.

Background: Fumigated, anaerobic soil disinfestation-treated (ASD), and organic-amended soil management strategies have been investigated as potential methyl bromide (MBr) alternatives for controlling diseases, nematodes, and weeds in soil. Nutsedge and broadleaf weed control using fomesafen has been reported to be comparable to MBr in normal cropping systems. There is no information on the fate of fomesafen used in combination with alternative practices. In this study, the fate of fomesafen in these alternative systems was measured by liquid chromatography-tandem mass spectrometry (LC/MS-MS) following extraction using a modified Quick Easy Cheap Effective Safe (QuEChERS) method., Results: The reported half-life (DT 50 ) values for fomesafen in the top 15 cm of soil were from 62.9 to 107.3 days. The DT 50 values in organic-amended soil were higher than in ASD-treated soil in the top 15 cm. For all treatments, reductions in concentrations were positively correlated with lower redox potentials and organic matter content. Some leaching of fomesafen into the 16-30 cm zone was observed in all treatments., Conclusions: The DT 50 values in this study were generally higher than those reported in previous studies performed at different locations. Due to increased losses of the herbicide and subsequent reduction in weed control, fomesafen is likely not to be suitable for effective weed control in systems using ASD techniques employing composted poultry litter and molasses. Integration of fomesafen using composted yard waste 1 (CYW1) and Soil Symphony Amendment (SSA) may result in acceptable weed control. Given that the soil was very sandy and the pH was higher than the pKa, fomesafen might leach deeper than 30 cm, particularly with the use of chemical soil fumigants (CSFs). © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The study of animal diet and feeding behaviour is a fundamental tool for the illustration of the ecological role of species in the ecosystem. However, size and quality of food intake samples make it hard for researchers to describe the diet composition of many small species. In our study, we exploited genomic tools for the analysis of the diet composition of the Savi's pine vole (Microtus savii) using DNA barcoding and qPCR techniques for the identification of ingested plant species retrieved from stomach contents. In contrast with previous studies, we found that, despite being a fossorial species, the Savi's pine vole is a selective feeder that undergoes intense superficial activity in search for food. In addition, our study shows that with a a priori knowledge of the candidate plant species included in animal diet, qPCR is a powerful tool to assess presence/absence, frequency of occurrence and electivity of ingested species. We conclude that this approach offers new opportunities to implement the analysis of food selection in small animals, thereby revealing a detailed picture of plant-animal interactions.

Background: Effectiveness of music-based interventions (MI) on cancer patients' anxiety, depression, pain and quality of life (QoL) is a current research theme. MI are highly variable, making it challenging to compare studies., Objective and Methods: To summarize the evidence on MI in cancer patients, 40 studies were reviewed following the PRISMA statement. Studies were included if assessing at least one outcome among anxiety, depression, QoL and pain in patients aged ≥ 18, with an active oncological/onco-haematological diagnosis, participating to any kind of Music Therapy (MT), during/after surgery, chemotherapy or radiotherapy., Results: A positive effect of MI on the outcomes measured was supported. Greater reductions of anxiety and depression were observed in breast cancer patients. MI involving patients admitted to a hospital ward were less effective on QoL., Conclusion: The increasing evidence about MI effectiveness, tolerability, feasibility and appreciation, supports the need of MI implementation in Oncology, Radiotherapy and Surgery wards, and promotion of knowledge among health operators., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The estimation of the values of a variable at any point of a study area is performed using Bernstein polynomials when the sampling scheme is implemented by selecting a point in each polygon of a regular grid overimposed onto the area. The evaluation of the precision of the resulting estimates is investigated under a completely design-based framework. Moreover, as the main contribution to the mean squared error of the Bernstein-type estimator is due to the bias, also a pseudo-jackknife estimator is proposed. The performance of both estimators is investigated theoretically and by means of a simulation study. An application to a soil survey performed in Berkshire Downs in Oxfordshire (UK) is considered., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Careful analysis of any new nanomedicine device or disposal should be undertaken to comprehensively characterize the new product before application, so that any unintended side effect is minimized. Because of the increasing number of nanotechnology-based drugs, we can anticipate that regulatory authorities might adapt the approval process for nanomedicine products due to safety concerns, e.g., request a more rigorous testing of the potential toxicity of nanoparticles (NPs). Currently, the use of mesoporous silica nanoparticles (MSN) as drug delivery systems is challenged by a lack of data on the toxicological profile of coated or non-coated MSN. In this context, we have carried out an extensive study documenting the influence of different functionalized MSN on the cellular internalization and in vivo behaviour. In this article, a synthesis of these works is reviewed and the perspectives are drawn. The use of magnetic MSN (Fe 3 O 4 @MSN) allows an efficient separation of coated NPs from cell cultures with a simple magnet, leading to results regarding corona formation without experimental bias. Our interest is focused on the mechanism of interaction with model membranes, the adsorption of proteins in biological fluids, the quantification of uptake, and the effect of such NPs on the transcriptomic profile of hepatic cells that are known to be readily concerned by NPs' uptake in vivo, especially in the case of an intravenous injection.

Purpose: An increasing number of patients complain about unsatisfactory aesthetic outcomes of orthognathic surgery, desiring reoperation to improve facial aesthetics. The aims of this article are to present a wide range of aesthetic reasons to justify a secondary orthognathic surgery and to report aesthetic outcomes and patient satisfaction after reoperation., Material and Methods: This research covers 70 consecutive patients who underwent a secondary bimaxillary orthognathic surgery with simultaneous facial lipofilling procedures between January 2006 and December 2015. The screening criteria are described for patient selection, the diagnostic process, surgical procedures, and outcomes. Pre- and postoperative facial appearances are compared. Postoperatively, patients were asked to state the improvements perceived in their facial appearance and their satisfaction with the aesthetic outcomes., Results: After reoperation, all patients showed a full Class I occlusion. Major complications did not occur. According to the clinicians' evaluation, a postoperative evident aesthetic improvement was achieved in 65 patients (92.9%), and 64 patients (91.4%) were satisfied with the aesthetic outcomes achieved., Conclusion: Secondary orthognathic surgery performed in conjunction with facial lipofilling procedures in most cases led to satisfactory aesthetic outcomes. A very accurate selection of patients, a meticulous three-dimensional diagnostic process and planning, and appropriate intra-operative maneuvers are required., (Copyright © 2017. Published by Elsevier Ltd.)

Up-regulation of the dystrophin-related gene utrophin represents a promising therapeutic strategy for the treatment of Duchenne Muscular Dystrophy (DMD). In order to re-program the utrophin expression level in muscle, we engineered artificial zinc finger transcription factors (ZF-ATFs) that target the utrophin 'A' promoter. We have previously shown that the ZF-ATF "Jazz", either by transgenic manipulation or by systemic adeno-associated viral delivery, induces significant rescue of muscle function in dystrophic "mdx" mice. We present the full characterization of an upgraded version of Jazz gene named "JZif1" designed to minimize any possible host immune response. JZif1 was engineered on the Zif268 gene-backbone using selective amino acid substitutions to address JZif1 to the utrophin 'A' promoter. Here, we show that JZif1 induces remarkable amelioration of the pathological phenotype in mdx mice. To investigate the molecular mechanisms underlying Jazz and JZif1 induced muscle functional rescue, we focused on utrophin related pathways. Coherently with utrophin subcellular localization and role in neuromuscular junction (NMJ) plasticity, we found that our ZF-ATFs positively impact the NMJ. We report on ZF-ATF effects on post-synaptic membranes in myogenic cell line, as well as in wild type and mdx mice. These results candidate our ZF-ATFs as novel therapeutic molecules for DMD treatment., (Copyright © 2018. Published by Elsevier B.V.)

Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized. In comparison, PEG M-MSNs showed a slower cellular uptake. Whole gene expression profiling revealed the M-MSNs molecular modes of action in a time- and dose-dependent manner. The lowest dose tested (1.6 µg/cm 2 ) induced no molecular effect and was defined as 'No Observed Transcriptional Effect level.' The dose 16 µg/cm 2 revealed nascent but transient effects. At the highest dose (80 µg/cm 2 ), adverse effects have clearly arisen and increased over time. The limit of biocompatibility for HepaRG cells could be set at 16 µg/cm 2 for these NPs. Thanks to a comparative pathway-driven analysis, we highlighted the sequence of events that leads to the disruption of hepatobiliary system, elicited by the three types of M-MSNs, at the highest dose. The Adverse Outcome Pathway of hepatic cholestasis was implicated. Toxicogenomics applied to cell cultures is an effective tool to characterize and compare the modes of action of many substances. We propose this strategy as an asset for upstream selection of the safest nanocarriers in the framework of regulation for nanobiosafety.

The formation of a protein corona around nanoparticles can influence their toxicity, triggering cellular responses that may be totally different from those elicited by pristine nanoparticles. The main objective of this study was to investigate whether the species origin of the serum proteins forming the corona influences the in vitro toxicity assessment of silica nanoparticles. Coronas were preformed around nanoparticles before cell exposures by incubation in fetal bovine (FBS) or human (HS) serum. The compositions of these protein coronas were assessed by nano-LC MS/MS. The effects of these protein-coated nanoparticles on HepG2 cells were monitored using real-time cell impedance technology. The nanoparticle coronas formed in human or fetal bovine serum comprised many homologous proteins. Using human compared with fetal bovine serum, nanoparticle toxicity in HepG2 cells decreased by 4-fold and 1.5-fold, when used at 50 and 10μg/mL, respectively. It is likely that "markers of self" are present in the serum and are recognized by human cell receptors. Preforming a corona with human serum seems to be more appropriate for in vitro toxicity testing of potential nanocarriers using human cells. In vitro cytotoxicity assays must reflect in vivo conditions as closely as possible to provide solid and useful results.

Radiofrequency (RF) catheter ablation is the treatment of choice in patients with accessory pathways (APs) and Wolff-Parkinson-White syndrome. Endocardial catheter ablation has limitations, including the inability to map and ablate intramural or subepicardial APs. Some of these difficulties can be overcome using an epicardial approach performed through the epicardial venous system or by percutaneous catheterisation of the pericardial space. When a suspected left inferior or infero-paraseptal AP is refractory to ablation or no early activation is found at the endocardium, a transvenous approach via the coronary sinus is warranted because such epicardial pathways can be in close proximity to the coronary venous system. Associated congenital abnormalities, such as right atrial appendage, right ventricle diverticulum, coronary sinus diverticulum and absence of coronary sinus ostium, may also hamper a successful outcome. Percutaneous epicardial subxiphoid approach should be considered when endocardial or transvenous mapping and ablation fails. Epicardial mapping may be successful. It can guide and enhance the effectiveness of endocardial ablation. The finding of no epicardial early activation leads to a more persistent new endocardial attempt. When both endocardial and epicardial ablation are unsuccessful, open-chest surgery is the only option to eliminate the AP., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.

In order to direct nanocarriers to their targets efficiently, we have to understand the interactions occurring at the nano-bio interface between nanocarriers and human proteins, which forms the layer called the corona. However, experiments aiming to identify and quantify the proteins in the corona, especially critical steps in the separation of nanoparticles from biological media may affect the corona composition. Here, we used nano-LC MS/MS to compare the protein corona contents obtained after using two different separation methods. We showed that applying centrifugation versus magnetization to isolate nanoparticles surrounded by a corona resulted in protein loss and a reshuffling of their respective abundances.

Purpose: This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis., Materials and Methods: DNMT1 rs2228611, DNMT3A rs1550117, DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC)., Results: Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade ≥ 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710)., Conclusion: DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.