Search

mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5–11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. Sixty children (26 [43 %] female, median age = 8 years [IQR = 7–10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. These findings provide insights into boosting pre-existing immunity. [ABSTRACT FROM AUTHOR]

Amyloid fibril formation by the extracellular protein β2-microglobulin (β2m) and its subsequent accumulation in periarticular tissues have been linked to dialysis-related amyloidosis. A natural variant of human β2m responsible for aggressive systemic amyloidosis contains an aspartate to asparagine mutation at residue 76 (i.e. D76N β2m), which readily forms amyloid fibrils in vitro under physiological conditions. In this study, we examined the role of the extracellular molecular chaperone clusterin in modulating D76N β2m fibril formation in vitro under physiological conditions. The presence of extrinsic charged amino acids modulated D76N β2m fibril formation, implying that electrostatic interactions are involved in the protein's aggregation. Thioflavin T (ThT) and 1-anilinonaphthalene-8-sulfonate fluorescence assays indicated that clusterin interacts via hydrophobic and electrostatic forces with the monomeric, prefibrillar and fibrillar species of D76N β2m. As a result, clusterin was incorporated into D76N β2m aggregates during the latter's fibril formation, as indicated by SDS-PAGE of depolymerised fibrils. SYPRO Orange and ThT fluorescence assays suggested that, compared to pure D76N β2m fibrils, those formed in the presence of clusterin are chemically more stable with a reduced ability to act as nucleation seeds. Detailed 15N NMR relaxation studies of mixtures of 15N-labelled β2m with clusterin confirmed that the chaperone interacts transiently and non-specifically with monomeric β2m. Clusterin inhibits both primary and secondary nucleation of D76N β2m fibril formation. In doing so, clusterin binds to D76N β2m fibrils and stabilises them to prevent possible fragmentation. In vivo , the multifaceted chaperone action of clusterin may delay, if not prevent, β2m amyloid proliferation and deposition in tissues. Accumulation of β2-microglobin in tissues is responsible for the disease dialysis-related amyloidosis. The D76N mutant is highly amyloidogenic. An in vitro biophysical and spectroscopic investigation of D76N β2-microglobin amyloid fibril formation and its inhibition by the common extracellular chaperone, clusterin, is described. In vivo , clusterin may play an important role in preventing β2-microglobin deposition. CH23082_TOC.jpg [ABSTRACT FROM AUTHOR]

There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed. Inflammatory, immunologic, and metabolic profiles were used to create a single algorithm (RBT index) predicting LC survival. A concurrent cohort of patients with resectable lung metastases (LM) was used to validate the RBT index. Charts of 2088 consecutive LC and 1129 LM patients undergoing lung resection were evaluated. Among RBT parameters, C-reactive protein (CRP), lymphocytes, neutrophils, hemoglobin, albumin and glycemia independently correlated with survival, and were used to build the RBT index. Patients with a high RBT index had a higher 5-year mortality than low RBT patients (adjusted HR 1.93, 95% CI 1.62–2.31). High RBT patients also showed a fourfold higher risk of 30-day postoperative mortality (2.3% vs. 0.5%, p 0.0019). The LM analysis validated the results of the LC cohort. We developed a simple and easily available multifunctional tool predicting short-term and long-term survival of curatively resected LC and LM. Prospective external validation of RBT index is warranted. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to offer a preliminary exploration into the key factors underlying trust in healthcare systems around the world, in light of the COVID-19 global pandemic. Participants were recruited across ten countries and were asked to complete a two-part questionnaire, in which they rated their country's healthcare system on a scale from 1-5, according to ten trustrelated factors, translated specifically to pertain to healthcare, and 4 key pillars of trust: benevolence, reliability, competence and predictability. Correlation analyses between these two separate measures revealed that honesty, consistency, and reasonableness were the most impactful factors underlying trust across the entire population. All other findings are detailed in the main text. This study allowed us to arrive at a preliminary determination of the most impactful factors underlying trust, both at a global and national level. [ABSTRACT FROM AUTHOR]

This population-based study aimed at providing an overview of drug prescription patterns during pregnancy in the Italian region of Lombardy from 2010 to 2020. The cohort consisted of 780,075 deliveries identified from the regional healthcare utilization databases. The prevalence of drugs' dispensed prescriptions was estimated as the proportion of pregnant women with at least one prescription out of the total deliveries over the entire pregnancy and by trimester. Drugs were classified according to the Anatomical Therapeutic Chemical code. In addition, interrupted time series analysis was conducted to investigate temporal trends of antibiotics' use during the onset of the COVID-19 pandemic. A total of 497,515 women (63.8%) used at least a drug, including vitamins and minerals, at some point during pregnancy. Vitamins, minerals, and anti-anaemic preparations were prescribed in 20.8%, 13.3%, and 18.3% of deliveries over the trimesters of pregnancy. Folic acid was the most prescribed drug, with about one woman out of four, followed by iron preparations, progestogen, and antibiotics (prescription rate, respectively: 15.9%, 10.2%, and 9.8%). A decreasing trend in the dispensing of antibiotics emerged during the entire study period; however, a significant further decrease following the spread of the pandemic was observed. Further evidence is needed to monitor the use of drugs during pregnancy, determinants, and implications. [ABSTRACT FROM AUTHOR]

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007–2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21–29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception. [ABSTRACT FROM AUTHOR]

Hypothesis: The aim of the study was to evaluate the correlation between NTproBNP and left ventricular mass (LVM) in children affected by hypertrophic cardiomyopathy (HCM), both asymptomatic, symptomatic, and with implantable cardioverter-defibrillator (ICD).A total of 225 pediatric patients were evaluated and 45 were enrolled in the study because met inclusion criteria (age < 18 years; diagnosis of hypertrophic cardiomyopathy; NTproBNP > 600 pg/ml).The analysis showed a significant correlation between NTproBNP level and LVM (p = 0.024). ANOVA test showed that high level of NTproBNP and LVM were significantly correlated to ICD implantation (p = 0.001; p = 0.003). Multivariate analysis showed NTproBNP as an independent risk factor for ICD implantation (p = 0.035).Our study showed that NTproBNP levels directly correlated to LVM and disease progression and it was found to be predictive, together with LVM, of ICD implantation.Methods: The aim of the study was to evaluate the correlation between NTproBNP and left ventricular mass (LVM) in children affected by hypertrophic cardiomyopathy (HCM), both asymptomatic, symptomatic, and with implantable cardioverter-defibrillator (ICD).A total of 225 pediatric patients were evaluated and 45 were enrolled in the study because met inclusion criteria (age < 18 years; diagnosis of hypertrophic cardiomyopathy; NTproBNP > 600 pg/ml).The analysis showed a significant correlation between NTproBNP level and LVM (p = 0.024). ANOVA test showed that high level of NTproBNP and LVM were significantly correlated to ICD implantation (p = 0.001; p = 0.003). Multivariate analysis showed NTproBNP as an independent risk factor for ICD implantation (p = 0.035).Our study showed that NTproBNP levels directly correlated to LVM and disease progression and it was found to be predictive, together with LVM, of ICD implantation.Results: The aim of the study was to evaluate the correlation between NTproBNP and left ventricular mass (LVM) in children affected by hypertrophic cardiomyopathy (HCM), both asymptomatic, symptomatic, and with implantable cardioverter-defibrillator (ICD).A total of 225 pediatric patients were evaluated and 45 were enrolled in the study because met inclusion criteria (age < 18 years; diagnosis of hypertrophic cardiomyopathy; NTproBNP > 600 pg/ml).The analysis showed a significant correlation between NTproBNP level and LVM (p = 0.024). ANOVA test showed that high level of NTproBNP and LVM were significantly correlated to ICD implantation (p = 0.001; p = 0.003). Multivariate analysis showed NTproBNP as an independent risk factor for ICD implantation (p = 0.035).Our study showed that NTproBNP levels directly correlated to LVM and disease progression and it was found to be predictive, together with LVM, of ICD implantation.Conclusion: The aim of the study was to evaluate the correlation between NTproBNP and left ventricular mass (LVM) in children affected by hypertrophic cardiomyopathy (HCM), both asymptomatic, symptomatic, and with implantable cardioverter-defibrillator (ICD).A total of 225 pediatric patients were evaluated and 45 were enrolled in the study because met inclusion criteria (age < 18 years; diagnosis of hypertrophic cardiomyopathy; NTproBNP > 600 pg/ml).The analysis showed a significant correlation between NTproBNP level and LVM (p = 0.024). ANOVA test showed that high level of NTproBNP and LVM were significantly correlated to ICD implantation (p = 0.001; p = 0.003). Multivariate analysis showed NTproBNP as an independent risk factor for ICD implantation (p = 0.035).Our study showed that NTproBNP levels directly correlated to LVM and disease progression and it was found to be predictive, together with LVM, of ICD implantation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate tissue repair of excisional wounds in hyperglycemic animals treated with chitosan-alginate membranes (CAM) produced in the presence of glycerol. 8-week C57B1 male mice were divided into normoglycemic animals with a 0.9% saline solution topical treatment (CTSF); hyperglycemic animals with 0.9% saline solution topical treatment (DMSF) and hyperglycemic animals with glycerol-plasticized chitosan-alginate membrane topical treatment (DMCAM). On post-wound day three, the DMCAM group presented a lower number of leukocytes, mature mastocytes, a higher number of vessels (p < 0.05), and active mastocytes (p < 0.05) when compared to the CTSF and DMSF groups. There were no differences regarding the distribution, deposition, organization, and thickness of collagen fibers. On day 7 there were no differences in the analysis of fibroblasts, mastocytes, and TGF−β1 and VEGF expressions among the groups. Regarding collagen fibers, the DMCAM group presented slight red-orange birefringence when compared to the CTSF and DMSF groups. On day 14 there was a slight concentration of thinner elastic fibers for the DMCAM group, with a greater reorganization of papillary skin and improved red-orange birefringence collagen fibers, as well as net-shaped orientation, similar to intact skin. In addition, improved elastic fiber organization distributed in the entire neo-dermis and a larger presence of elaunin fibers were observed, in a similar pattern found in the intact skin. The use of CAM in cutaneous lesions boosted tissue repair since there was a smaller number of inflammatory cells and mastocytes, and an improvement in collagen deposition and collagen fibers. These results demonstrate the high potential of plasticized chitosan-alginate membrane for skin wound dressing of hyperglycemic patients. [ABSTRACT FROM AUTHOR]

Speaking on one's own behalf and asserting one's entitlement to assess oneself are regular features of interaction, but participants often sound for others through practices like responsive animation, through which they are seen to be temporarily "doing being" others in a responsive slot. In this paper we study a collection of responsive animations consisting primarily of non-lexical vocalisations with gestural ensembles produced in contexts where territorial rights are in tension. We focus on environments where a participant engages in self-deprecating disclosures around past or projected negative happenings that may be shared by a co-participant (albeit experienced independently) and who animates an aspect of these in response. We describe how co-participants sound for each other by deploying animations that instead of minimising deprecating components, actually amplify them through a transformed and creative vocal and/or visual demonstration of a jointly negotiated (shared) attribute or experience. These animations create brief moments of heightened involvement and other-attentiveness before transitioning to a new/next order of conversational business. • While participants often speak on their own behalf they may engage in animation to sound for others. • Animation is a responsive option in contexts of co-participants' reciprocal my-side self-deprecating disclosures. • Brief animations designed as non-lexical vocalisations or gestural ensembles in this context amplify deprecating attributes and experiences. • Animation is used for joint appreciation and play and other-attentiveness before turning to other orders of conversational business. [ABSTRACT FROM AUTHOR]

Simple Summary: MIS-C is a multisystem inflammatory syndrome that is characterized by severe systemic signs of inflammation and multi-organ failure, including the involvement of the heart. Our study described the long-term cardiovascular outcome in a cohort of pediatric patients with MIS-C, who were admitted to two Italian Pediatric Referral Centers. The number of pediatric patients with an MIS-C diagnosis was 67. Among them, 65% of them had ventricular dysfunction, 66% of them had pericarditis, 35% of them had coronary involvement, and 9% of them showed arrhythmias. Our data described many cases of myocarditis and pericarditis, with mild coronary involvement and a few cases of arrhythmias. This experience showed that cardiac involvement in MIS-C patients is almost the rule, and that LV dysfunction and pericarditis are the most frequent manifestations of it. However, the patients' clinical course was satisfactory, and during the controls, no additional events or sequelae were observed apart from long-term myocardial scars in 50% of the patients that underwent CMR. Early treatment not only provides a prompt full recovery, but it also has a probably "protective" effect towards late adverse events and long-term complications. MIS-C is a multisystem inflammatory syndrome that is characterized by multi-organ failure and cardiac involvement. The aim of this study was to describe the long-term cardiovascular outcome in a cohort of MIS-C pediatric patients, who were admitted to two Italian Pediatric Referral Centers. Sixty-seven patients (mean age 8.7 ± 4.7 years, male 60%) were included; 65 (97%) of them showed cardiac involvement. All of the patients completed one month of the follow-up, and 47% completed 1 year of it. ECG abnormalities were present in 65% of them, arrhythmias were present in 9% of them during an acute phase and it disappeared at the point of discharge or later. Pericarditis were detected in 66% of them and disappeared after 6 months. Coronaritis was observed in 35% of the children during an acute phase, and there were no more instances at the 1-year point. An LV dysfunction was present in 65% of the patients at the beginning of the study, with them having a full recovery at the point of discharge and thereafter. Elevated values of the NTproBNP and hsTp were initially detected, which progressively decreased and normalized at the points of discharge and FU. The CMR at the point of FU, there was a presence of long-term myocardial scars in 50% of the patients that were tested. No deaths that were caused by MIS-C during the FU were recorded. Cardiac involvement in MIS-C patients is almost the rule, but the patients' clinical course was satisfactory, and no additional events or sequelae were observed apart from there being long-term myocardial scars in 50% of the patients that underwent CMR. [ABSTRACT FROM AUTHOR]

The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca2+) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca2+-bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop. [ABSTRACT FROM AUTHOR]

Studying the electrochemical behavior of colloidal particles is important for fertility management and soil conservation, since it enables the understanding of several physicochemical phenomena that occur in soils. The objective of this study was to determine the point of zero charge (PZC) and the electrochemical behavior of surface and subsurface samples of three Red-Yellow Latosols (Oxisols), with different mineralogical and textural characteristics, through potentiometric titration and ionic adsorption. The point of zero charge (PZC) and the electrochemical behavior were determined in samples from the A and B horizons of three Red-Yellow Latosols: very clayey kaolinitic (LVAcr), very clayey gibbsitic (LVAgr) and sandy loam kaolinitic (LVAcm). The analyses were conducted in soil samples with particle size smaller than 0.7 mm, with desaturation of aluminum (Al3+), and smaller than 2 mm, without desaturation. Solutions containing sodium (Na+) and nitrate (NO3−) as indifferent electrolytes were used in all methods. The LVAgr, even with higher organic matter contents, had higher PZC, indicating the importance of mineralogical composition for this characteristic. Among the two kaolinitic soils, there was higher PZC in LVAcm, with lower organic matter content; however, both soils had higher PZC in the B horizon than in the A horizon. The net electrical charge estimated by the potentiometric titration method was equivalent to the net charge estimated by the ionic adsorption method for horizons A and B of LVAgr and LVAcm. At the same time, there was underestimation of the net negative charge by the potentiometric titration method for the A and B horizons of LVAcr. [ABSTRACT FROM AUTHOR]

The aim of this study was to report clinical and arrhythmic features in a pediatric population affected by arrhythmogenic cardiomyopathy (ACM). Moreover, we assessed the concordance between the 2010 International Task Force criteria (ITF) and the 2020 Padua criteria. Inclusion criteria were "definite" or "borderline" ACM diagnosed according to the "Padua criteria" in patients <18 years old. History, electrocardiograms, ECG-holter monitorings, exercise testings, imaging investigations, electrophysiological studies, genetic testings and follow-up data were collected. We enrolled 21 patients (mean age 13.9 ± 2 years). Most of them presented for minor arrhythmias. Premature ventricular complexes burden was 7.9 ± 10%. Cardiac magnetic resonance (19/21, 90.5% patients) showed right ventricular (RV) dilatation, wall motion abnormalities and late gadolinium enhancement (LGE) of both ventricles as predominant features [in 9 patients (52.9%) LGE left ventricle]. Genetic results (19/21 patient) showed compound heterozygous variants in 3/19 patients (15.8%), digenic in 3/19 (15.8%) and single in 6/19 (31.6%). Cardiac defibrillator (ICD) was indicated in 15 patients (71.4%): 6 in class I, 7 in class IIa, 2 in class IIb. Appropriate shocks occurred in 2 patients (13.3%), follow-up 5.46 ± 3.17 years According to 2010 ITF criteria: among the 18 patients with a "definite" ACM diagnosis, one patient would have had a "borderline" diagnosis, three a "possible" diagnosis and one no diagnosis and among the three patients with "borderline" diagnosis two would have had a "possible" diagnosis. Pediatric ACM can be diagnosed in the majority of cases secondary to incidental finding of simple ventricular arrhythmias. PVC burden is low and exercise induced arrhythmias rarely occur. Few patients with ICD experience appropriate shocks. "Padua criteria" improve the diagnostic accuracy. • Arrhythmic incidental finding is the initial manifestation for the majority of patients. • Positive family history of arrhythmogenic cardiomyopathy/sudden cardiac death can help to identify the disorder Figure 1:, 2:, 3: and Supplementary Fig earlier. • Investigate polymorphic and complexes premature ventricular contractions is extremely important. • Most patients fulfill the indications for ICD implantation, but a minority experience arrhythmic events during follow-up. • "Padua criteria" improve the diagnostic accuracy of the arrhythmogenic cardiomyopathy also in the pediatric setting. [ABSTRACT FROM AUTHOR]

Through troubles-talk, participants disclose and negatively assess unfortunate past or habitual happenings and offenses, and these are often vividly staged in the here and now by temporarily "doing being" past Self or others, what we call animation. In this study, we show how by animating their own affective reactions toward the recounted experiences, tellers cast themselves as victims and their recipients as witnesses. More importantly, we demonstrate how animation is also a relevant practice for recipients, who in a contiguous position often offer a responsive co-animation of the same figure, validating and amplifying their teller's affective displays, turning the experience into a common cause. This study contributes further to our understanding of empathic responses in troubles-talk in English by inscribing co-animation as a previously undescribed alternative at the response slot that allows recipients to temporarily position themselves "into the moment" as co-victims, co-experiencers, and co-sanctioners. Data are in English. [ABSTRACT FROM AUTHOR]

Nitrate (NO3–-N) leaching in tropical soils, which are more weathered, is influenced by their mineralogical, physical, and chemical characteristics. Thus, the present study aimed to evaluate the effect of the variation of net electrical charge on the mobility of nitrate, applied as potassium nitrate (KNO3) or calcium nitrate (Ca(NO3)2), in samples from A and B horizons of three Red-Yellow Latosols (Oxisols), with different mineralogical and textural characteristics. Hydrochloric acid (HCl) or sodium hydroxide (NaOH) volumes were added to previously sterilized soil samples in order to condition five hydrogen potential (pH) values, obtaining different net electrical charges. The experiment was carried out with leaching columns under laboratory conditions. The soil columns were percolated with solutions of KNO3 or Ca(NO3)2 or water (control). An increase in positive net charges was significant and varied according to the soil and percolating solution; in general, it resulted in an increase of up to 50% in nitrate adsorption in some soils. Larger amounts of adsorbed nitrate were observed in the columns filled with the B horizon of the clayey gibbsitic Red-Yellow Latosol, showing adsorption of 85% for a positive net charge of 2 cmolc kg−1. Regarding kaolinitic soils, lower adsorption was observed in the medium-textured kaolinitic Red-Yellow Latosol, which had lower clay content and positive net charge. Application of Ca(NO3)2, as a percolating solution, increased nitrate adsorption compared to the application of KNO3. This effect may be attributed to the increase in positive net charge promoted by calcium (Ca2+), being more evident for the highest negative net charges. [ABSTRACT FROM AUTHOR]

We use the dissipative-type theory (DTT) framework to solve for the evolution of conformal fluids in Bjorken and Gubser flows from isotropic initial conditions. The results compare well with both exact and other hydrodynamic solutions in the literature. At the same time, DTTs enforce the Second Law of thermodynamics as an exact property of the formalism, at any order in deviations from equilibrium, and are easily generalizable to more complex situations. [ABSTRACT FROM AUTHOR]

Pregnant women who suffer from depressive disorders are likely to be treated with antidepressant (AD) medications. Recent meta-analyses underlined the possible relation between AD use and several neonatal outcomes, although the underlying mechanisms remains unclear. To summarise and evaluate the associations between AD use in pregnancy and neonatal outcomes, we conducted an umbrella review of meta-analyses of observational studies published up to December 2019 in PubMed and Embase. Summary risk estimates for the associations between use of AD as a whole, or specific AD classes and drugs, and the risk of neonatal outcomes were reported. Our review included 22 meta-analyses investigating 69 associations. However, none were supported by convincing evidence. Highly suggestive evidence regarded the associations between (i) any time AD exposure and the risk of preterm birth (relative risk, 1.68; 95% confidence interval 1.52, 1.86), (ii) any time exposure to selective serotonin reuptake inhibitors (SSRIs) and the risk of preterm birth (1.43; 1.22, 1.37) and (iii) respiratory distress (1.33; 1.14, 1.55), and (iv) SSRI exposure during the first trimester of pregnancy and the risk of cardiovascular malformations (1.25; 1.13, 1.39). Suggestive evidence was obtained for any time AD exposure on 1-min low Apgar score (absolute average difference, −0.34; −0.53, −0.14). Overall, the effects of AD exposure during pregnancy on neonatal outcomes have been extensively studied, but few of the associations are graded as high quality evidence. More prospective studies and large collaborations with comprehensive standardised reporting of analyses are needed. [ABSTRACT FROM AUTHOR]

The significant impact of acute respiratory tract infections on healthcare systems is well-documented, given their contribution to emergency department admissions, hospitalizations, and increased use of antibiotics and other medications. However, further research is needed to understand the burden of acute respiratory tract infections in pediatric community care to develop effective public health interventions and improve child health outcomes. Real-world data were retrieved from Pedianet, an Italian network of over 200 family pediatricians. Acute respiratory tract infection visits were identified and analysed using an infection-duration algorithm to extract individual cases. The number of follow-up visits per 100 cases was calculated to assess the burden on the Italian National Health Service. Comparisons were made overall and stratified by type of acute respiratory tract infections and epidemiological season. A total of 1,402,953 acute respiratory infections-related visits were recorded, with an overall rate of 12 visits per 100 cases. Upper respiratory tract infections had an average of 9 visits per 100 cases. Lower respiratory tract infections exhibited a higher burden, with 29 visits per 100 cases. Pneumonia showed a declining trend in the pre-pandemic era (62 to 48 visits) but rebounded in the post-COVID-19 years (32 to 42 visits). This study underscores the importance of monitoring and managing acute respiratory infections, especially lower respiratory tract infections, in pediatric care. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) allowed improved survival in the pediatric population and bridged successfully to heart transplant. The beneficial effect of LVAD encompasses LV unloading, leading to inverse remodelling. In some cases, recovery can result in significant improvement in cardiac function allowing LVAD removal. Some studies suggested medical therapy might play a role in promoting cardiac recovery combined with LVAD. Few data are currently available in children about a combined medical and LVAD strategy to induce myocardial recovery. To verify the hypothesis that a strategy including optimized LVAD unloading combined with maximized anti heart failure treatment (MaHFT) was effective to induce myocardial recovery. The primary outcome was LVAD explantation. This is a single center retrospective analysis of all patients with dilated cardiomyopathy or myocarditis receiving durable LVAD support from 2017 to 2022 at Bambino Gesù Children's Hospital in Rome. Patients' clinical data and outcomes were recorded. The MaHFT included: β blockers (carvedilol- 1 mg/kg/d or bisoprolol- 0.4 mg/kg/d), ACE inhibitors (enalapril 0.4 mg/kg/d) and a MRA (3 mg/kg/d). Ivabradine was added in those in which the heart rate was not reduced below the 20% from the baseline. Accordingly to the strategy all patients were divided in two groups: LVAD alone (group 1) or LVAD+MaHFT (group 2). A chi squared analysis was conducted in order to evaluate the beneficial effect of this strategy in terms of weaning of LVAD. 23 patients (14 M; age: 7,4 ± 7,2 years) underwent durable LVAD implantation from 2017 to 2022. At the time of implant, all patients were in PEDIMACS2. Pulsatile LVAD used in 17, and continuous LVAD in 6. 10 received MaHFT. In group 1, only one (1/13) reached the criteria for explantation while in the group 2, 8/10 reached the criteria for explantation and were weaned from LVAD (p = 0.002). After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 3 years. Whilst the numbers are small, these results demonstrate that a combined strategy of LVAD and MaHFT can lead to a significant increase in myocardial recovery permitting LVAD explanation with sustained myocardial recovery in at least the short to medium term. [ABSTRACT FROM AUTHOR]

Aims: Women with pre-existing diabetes should plan for optimal care of the disease before, during and after pregnancy. The aim of this study was to assess the quality of diabetes mellitus monitoring and care before, during and after pregnancy in a large cohort of women.Methods: 1913 diabetic women resident in the Lombardy Region (Italy) who experienced at least a birth between 2011 and 2015 and exhibited signs of diabetes ≥2 years before delivery were identified using the healthcare utilization database. Antidiabetic care was defined via outpatient examinations (i.e., assessments of glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine, and dilated eye exams) and use of antidiabetic drugs. Differences in adherence to recommendations before, during and after pregnancy were assessed by the non-parametric McNemar's test among the whole cohort and among the subgroup with type 1 diabetes.Results: Adherence to recommendations was very poor before pregnancy, ranging from 13% to 42% for dilated eye and serum creatinine exam, respectively. During pregnancy, a significant portion of women increased adherence to all recommendations (e.g., glycated haemoglobin from 20% to 47%, p-value < 0.001), with the exception of lipid profile control. After pregnancy, adherence dropped to pre-pregnancy levels. A similar trend was observed in the use of antidiabetic drugs. Although women with type 1 diabetes showed better adherence across all periods, the same patterns emerged.Conclusions: Besides an improvement in the indicators of clinical adherence during pregnancy, the management of diabetes among pregnant women remains sub-optimal both before and after the birth. [ABSTRACT FROM AUTHOR]

This paper presents a multinomial method for option pricing when the underlying asset follows an exponential Variance Gamma (VG) process. The continuous time VG process is approximated by a continuous time process with the same first four cumulants and then discretized in time and space. This approach is particularly convenient for pricing American and Bermudan options, which can be exercised before the expiration date. Numerical computations of European and American options are presented and compared with results obtained with finite differences method and with the Black-Scholes prices. [ABSTRACT FROM AUTHOR]

DCM is the leading cause of death in Duchenne patients. LVADs are considered as therapeutic options as DT in advanced HF. The aim of our study was to evaluate LV remodeling of Duchenne after LVADs and chronic therapy. Demographic and echocardiographic data of 8 Duchenne patients implanted with LVADs were reviewed and analyzed. All measures were collected before LVAD implantation, after 1 month and 1 year. All patients were affected by end‐stage DCM, and mean age at implantation was 16.9 ± 2.9 years. Patients were treated with maximal medical therapy. One‐year post‐implantation HR decreased from a mean of 110 ± 19 bpm to 82 ± 2 bpm (P =.002), and a significant decrease in LV volumes and diameters LVEDD P =.03, LVESD P =.02, EDV P =.01, and ESV P =.02) was noticed together with a significant increase in EF (P =.0036). However, RWT did not change over time, showing an eccentric remodeling pattern pre‐ and post‐LVADs. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function secondary to a significant ventricular unloading due to LVADs coupled with chronic therapy. [ABSTRACT FROM AUTHOR]

Abstract National healthcare systems of advanced countries, including Italy, widely agree on the approach whereby public healthcare decisions should be driven by available evidence on effectiveness and safety of therapeutics. It is equally accepted that randomized controlled clinical trials (RCTs), although universally recognised as the most robust "evidence generators", are insufficient for guiding the decision-making process since they are intrinsically unsuited to capture the impact of treatments in routine clinical practice. The complexity of treatments, as well as the demographic and clinical heterogeneity of patients receiving the treatments, and the long period of many treatments, explain the gap between the evidence generated in the controlled, but artificial, setting of RCTs and their current impact in the real world. The so-called pragmatic RCTs, despite guaranteeing greater flexibility compared to conventional trials, are not always able to reduce this gap. This explains the growing interest in the development of methods able to produce evidence on the real-world impact of care pathways (i.e. , real-world evidence). Among them, those based on the Electronic Healthcare Records (EHRs), as the databases on the healthcare services of the National Health System provided to beneficiaries, known as Healthcare Utilization Databases (HCU), are becoming established and receiving increasing attention from the scientific community and healthcare decision-makers. We described the research areas in which HCU databases may be particularly useful, jointly with strength, weakness and potential of this approach. It is concluded that HCU data cannot substitute RCTs but they can usefully complement RCT data for adequately supporting healthcare decision-makers. [ABSTRACT FROM AUTHOR]

Background Heterotaxy syndrome (HS) is a group of congenital disorders characterized by abnormal arrangement of thoraco-abdominal organs across the left-right axis of the body, classified as right (RAI) and left atrial isomerism (LAI)·We investigated the long-term survival and phenotypic spectrum in our HS cohort. Results are compared to literature data. Methods This is a single centre, observational, both retro and prospective study. Cardiac features, surgical management and abdominal ultrasound (US) of all HS patients were reviewed or investigated if missing. We evaluated all anatomical data and their clinical impact on survival, arrhythmias, infections, and heart transplant (HT). Results 136 patients were classified as RAI (81) and LAI (55). Long-term survival and freedom from HT reached 69.8% and 87.8% at 40 years in RAI and LAI, respectively. Multivariate analysis showed that LAI is an independent predictor for pacemaker implantation (p = 0.019). Splenic status varied in both groups: in RAI, abdominal US showed asplenia, polysplenia and normal spleen in 48%, 4% and 32% of patients, respectively, whereas in LAI polysplenia, asplenia and normal spleen occurred in 64%, 4% and 16% of cases, respectively. Conclusions Mortality was significantly lower (9%) compared to literature (50%). Although patients with RAI experienced a higher mortality, no independent predictors were found. We demonstrated that the obsolete cardiac definition of “asplenia” and “polysplenia” instead of RAI and LAI is misleading, because of the high variability of the splenic phenotype among patients of both groups. [ABSTRACT FROM AUTHOR]

Type II phosphatidylinositol 4-kinase (PI4KII) is thought to be associated with synaptic vesicles (SVs) and to be responsible for the majority of PI4K activity in the nervous system. However, the function of PI4KII at the synapse is unknown. We characterized the synaptic phenotypes of a Drosophila melanogaster PI4KII null mutant. We found increased nerve terminal growth in PI4KII null mutants indicating that PI4KII restrains nerve terminal growth. Evoked neurotransmitter release elicited in response to low frequency stimulation and spontaneous neurotransmitter release were not altered in PI4KII null mutants. However, PI4KII null mutants displayed reduced FM1-43 uptake in response to stimulation by high K+ saline, indicating impaired SV endocytosis. PI4KII null mutants did not display any defects in FM1-43 unloading, consistent with normal SV exocytosis. Thus, PI4KII is required for SV endocytosis but dispensable for SV exocytosis. Overall, our data show that PI4KII regulates both nerve terminal growth and SV recycling. [ABSTRACT FROM AUTHOR]

Protein fibrillation is involved in many serious diseases, and protein oligomers are proved to be precursors of amyloid fibrils. NMR and QCMD experiments allowed us to establish that the interaction between citrate-stabilized gold nanoparticles and a paradigmatic amyloidogenic protein, β2-microglobulin, is able to interfere with protein association into oligomers. [ABSTRACT FROM AUTHOR]

Background Recent estimates indicate an increase in the prevalence of skin diseases in children. Few large epidemiologic studies have examined prevalence trends in Europe. This study evaluated the incidence and prevalence of frequently occurring pediatric skin diseases ( PSDs) in Italy as seen by family pediatricians ( FPs). Methods Data were retrospectively extracted from the Pedianet database (2006-2012) in children ages 0 to 14 years presenting with a skin disease at their FP. The incidence and prevalence estimates were calculated per year and stratified according to sex, age, and geographic area. Results A mean of 145,233 children (52.1% male) across five Italian regions were registered with their participating FP for a total of 913,253 person-years of follow-up. The majority of patients were from the northeast (44.6%) and 37.7% were ages 5-9 years. Incidence estimates (new cases/1,000 person-years) for most PSDs increased from 2006 to 2012, the highest being for atopic dermatitis ( AD) (14.1 vs 16.5), acute urticaria (10.1 vs 11.6), and contact dermatitis (9.3 vs 10.8), whereas psoriasis remained unchanged over the 7 years (0.61 vs 0.57). In contrast, prevalence estimates (cases/100 patients) increased two to three times for several PSDs, including AD (2.7% vs 8.5%), seborrheic dermatitis (0.5% vs 1.6%), chronic urticaria (0.4% vs 0.8%), and psoriasis (0.09% vs 0.22%). Differences in prevalence according to age range and geographic area were observed for psoriasis, AD, and urticaria. Conclusion This study provides comprehensive evidence of the increasing prevalence and incidence of PSDs across Italy. Additional causality studies to address this important clinical and psychosocial problem are recommended. [ABSTRACT FROM AUTHOR]

Rock phosphate (RP) shows reduced dissolution in soils amended with limestone and when applied through spot application. A simple way to improve RP efficiency under these unfavorable conditions may be the combination with nitrogen (N) fertilizers which can increase the solubilization of apatite minerals and/or stimulate P uptake. In this context, we evaluated the agronomic effectiveness of a RP from Bayóvar, Peru (BY), combined with different N sources in spot application, in a clayey Oxisol (Typic Hapludox). The pot experiment consisted of a factorial scheme (3 × 2 × 2+4) in randomized block design with four replications. Treatments consisted of BY combined with three N sources (ammonium sulfate-BY+AS; urea-BY+U; potassium nitrate-BY+KN), in two forms (granulated or powdered), and in two N : P molar ratios (0.5 : 1.0 or 1 : 1) and four additional treatments [control: without P; monoammonium phosphate (MAP); powdered BY; granulated BY]. The products were incorporated into a 50 cm3 cylindrical soil volume (central and upper position in the pot: diameter 17 cm and height 15 cm) with three maize plants ( Zea mays L.). Above-ground biomass was sampled after 42 d after sowing, analyzed for N and P concentrations to calculate N and P uptake. Soil samples were taken from the cylindrical soil volume and measured for RP dissolution (ΔCa index), P availability (P-resin index), and soil pH. Application of MAP increased soil P availability about 11 times compared with BY treatments. As a result, maize plants grew 3.8 times and absorbed 7.3 and 3.3 times more P and N compared to those fertilized with BY combined with N fertilizers. Compound fertilizers BY+AS and BY+KN had the same effect on N and P uptake, presenting an effectiveness about 12 and 19% greater than pure BY, respectively. Compound fertilizers with BY+AS were more effective in powdered form (with no N/P ratio effect), while BY+KN was more effective in granulated form and in 1 : 1 N : P ratio. BY+U combinations were less efficient in promoting plant P bioavailability than the other N sources. We conclude that Bayóvar RP has a low agronomic effectiveness for spot application, even when combined with N. [ABSTRACT FROM AUTHOR]

Background: Maternal socioeconomic disparities strongly affect child health, particularly in low and middle income countries. We assessed whether neonatal outcomes varied by maternal education in a setting where healthcare system provides universal coverage of health services to all women, irrespective of their socioeconomic status.Methods: A population-based study was performed on 383,103 singleton live births occurring from 2005 to 2010 in Lombardy, an Italian region with approximately 10 million inhabitants. The association between maternal education, birthplace and selected neonatal outcomes (preterm birth, low birth weight, small-for-gestational age, low 5-min Apgar score, severe congenital anomalies, cerebral distress and respiratory distress) was estimated by fitting logistic regression models. Model adjustments were applied for sociodemographic, reproductive and medical maternal traits.Results: Compared with low-level educated mothers, those with high education had reduced odds of preterm birth (Odds Ratio; OR = 0.81, 95% CI 0.77-0.85), low birth weight (OR = 0.78, 95% CI 0.70-0.81), small for gestational age (OR = 0.82, 95% CI 0.79-0.85), and respiratory distress (OR = 0.84, 95% CI 0.80-0.88). Mothers born in a foreign country had higher odds of preterm birth (OR = 1.16, 95% CI 1.11-1.20), low Apgar score (OR = 1.18, 95% CI 1.07-1.30) and respiratory distress (OR = 1.19, 95% CI 1.15-1.24) than Italian-born mothers. The influence of maternal education on neonatal outcomes was confirmed among both, Italian-born and foreign-born mothers.Conclusions: Low levels of education and maternal birthplace are important factors associated with adverse neonatal outcomes in Italy. Future studies are encouraged to investigate factors mediating the effects of socioeconomic inequality for identifying the main target groups for interventions. [ABSTRACT FROM AUTHOR]

Background: Untreated depression during pregnancy increases the risk of morbidity and mortality in the mother and child. Therefore, specific treatments are required for this population. Objective: The study aimed to investigating the effect of antidepressant medication used during pregnancy with reference to the risk of preterm birth (PTB) and low birth weight (LBW). Methods: A population-based study was carried out with data provided by the healthcare utilization database of Lombardy, an Italian region with about ten million inhabitants. The study included 384,673 births from 2005 to 2010. Maternal use of antidepressants before and during pregnancy was investigated. Log-binomial regression was used to estimate the association between the use of antidepressants during pregnancy, compared to the non-use or use just before pregnancy, and the prevalence ratio of PTB and LBW. Results: Women who used antidepressants during pregnancy had a 20% (95% CI: 10–40%) increased prevalence of both PTB and LBW compared to those who never used antidepressants. There was no evidence that women who used antidepressants during pregnancy had a higher prevalence of the considered outcomes compared to women who used antidepressants before pregnancy, but stopped during pregnancy. Such findings were confirmed by considering separately the effects of SSRIs and other antidepressants together. Conclusions: Our findings suggest that depression in itself, rather than antidepressant medication, might be implicated in the causal pathway of PTB and LBW. [ABSTRACT FROM AUTHOR]

To analyze the occurrence of disability pension and its association with physical inactivity and nutritional condition, isolated and aggregated way, in Brazilian National Health System patients aged ≥50 years-old, in 2013. 542 adults of both sexes, with a mean age of 61.9 years (95% CI = 61.2, 62.7) were evaluated in two Basic Health Units. Body mass index (kg/m²) was calculated and disability pensions, habitual physical activity and presence of diseases were self-reported. Variable cluster of physical inactivity and obesity was created with the aim to analyze together physical activity and nutritional status. In overall sample, the occurrence of disability pension was 25.6% (95%CI= 21.9% - 29.3%), which it was associated with cluster of obesity and physical inactivity (OR= 2.26 [95%CI: 1.14; 4.47]) when model was adjusted for heart attack, osteoporosis, arthritis / arthrosis, disc herniation and low back pain. It is concluded that the occurrence of disability pension was higher than 25% and significantly related to cluster of obesity and physical inactivity. [ABSTRACT FROM AUTHOR]

Aim: Children have largely been unaffected by severe COVID‐19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID‐19 and healthy controls. Methods: A retrospective nested cohort study assessed the incidence rate of new‐onset conditions after COVID‐19 in children aged 0–14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. Results: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new‐onset conditions after COVID‐19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1–3.0) and neurological problems (aHR 2.4, 95% CI 1.4–4.1). Conclusion: Exposed children had a 78% higher risk of developing new conditions of interest after COVID‐19 than unexposed children. [ABSTRACT FROM AUTHOR]

Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described. We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity. Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated. [ABSTRACT FROM AUTHOR]

We aimed to measure and validate differences in plasma concentrations of proteins that are associated with prognosis in children with idiopathic PAH and due to CHD to improve risk stratification. Pulmonary arterial hypertension (PAH) in children is a complex and heterogenous condition, mostly complicating congenital heart disease (CHD) and carrying an increased risk of mortality. Clinical management is difficult due to the scarcity of data to have an accurate assessment of risk in this subgroup of patients. In this observational cohort study, we enrolled 29 children (mean age: years 13.8±10.7, median: 10) with PAH, idiopathic and due to CHD. Blood samples were collected at routine clinical appointment visits. In the same day, all data for clinical status, biochemical and no-invasive tests were collected. Clinical data within 1 year of follow up have been recorded. We used an aptamer-based assay of 1000 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against multiparametric clinical assessment or natriuretic peptides. The primary endpoint was a combination of life threatening arrhythmias, rehospitalization and death. 3 proteins differentiated worse prognosis in 29 consecutive patients with PAH with 1 year of follow-up. 3 proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to inflammatory cascade and myocardial stress and coagulation. A combination of three circulating proteins identifies patients with PAH with a high risk of arrhythmia and hospitalization, independent of existing clinical assessments, and might have a use to stratify the risk in children. [ABSTRACT FROM AUTHOR]

An elevated heart rate (HR) is associated with an increased risk of death and cardiac transplant in children with dilated cardiomyopathy (DCM). Whether HR is a biologic marker to address therapy is poorly investigated in pediatric age. Aim The purpose of this study is to investigate the relationship between HR and LVEF improvement in a pediatric population of patients affected by DCM with reduced LVEF and treated with carvedilol. A retrospective analysis has been conducted on all children (aged < 18 years) followed by HF Unit in Bambino Gesù Children Hospital from 2013 with a diagnosis of DCM and reduced LVEF (LVEF < 40%) treated by HRR strategy with high dosage of carvedilol. Echocardiographic data on left ventricular function and dimension have been collected. We analysed the relationship between HRR and left ventricular remodelling: LVEF, end-diastolic (LVEDd) and end-systolic left ventricular diameters (LVESd) before and after HRR treatment. The relation between change in HR, LVEF, LVEDs and LVESd were determined using regression analysis. 65 patients have been selected (M: 38; age 8.7+/- 8.9). The average LVEF was 32+/-9.4 before treatment. All patients were treated with anti HF therapy, including beta-blocker, carvedilol, up titrated to the maximal tolerated dose. We observed a statistically significant relationship between change in HR and change in LVEF (R 0.40; p = 0.001). In particular a HRR of > 20% from basal HR value was related with an improvement > of 25% in LVEF. The magnitude of LVEF improvement was enhanced by a major reduction in HR. This study provide evidence that heart rate reduction is safe in children. There is a strong correlation with LVEF improvement in children affected by DCM. [ABSTRACT FROM AUTHOR]

Background Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality in patients affected by Duchenne muscular dystrophy (DMD). DCM is commonly characterized by a hypokinetic and dilated phenotype, typically involving left ventricle (LV). Nowadays, angiotensin converting enzyme inhibitors (ACEi) are indicated in all patients older than 10 years but the mechanism of action is still unknown. Characteristics of left ventricular (LV) remodelling are unclear, and no data are currently available on the time of onset. Aim: characterize left ventricular remodelling before 10 years of age and the effects of ACEi on it. We conducted a retrospective single center analysis on all consecutive patients affected by DMD-DCM before 10 years of age, without LV dilation. We reanalysed all echocardiographic data about LV dimension and function, at the first cardiovascular assessment (before ACEi), at one year after treatment, and at the last follow up. To evaluate LV remodelling, we derived the relative wall thickness (RWT). RWT< 0.32 was the cut off to define the cardiac atrophy. 45 patients have been enrolled. Median age at first CV assessment was 10.3 y (±2.9). 72% of patients presented a reduced RWT (< 0.32) at first CV evaluation (average value 0.29 ± 0.05). After 1 year of treatment the percentage of patient with cardiac atrophy was unchanged (p = 0.52): 6 patients progressed and 6 regressed. At last follow up (35.5 months, ±7.7) the prevalence of cardiac atrophy was slightly increased (78% - p = 0.15): 9 patients (28%) developed cardiac atrophy during follow-up, despite ACEi therapy, while 6 (19%) regressed. Notably, neither progression nor regression were statistically significant (p= 0.15, p = 0.4 respectively). All patients were treated with ACEi: 48% was treated with Enalapril, 26% with Ramipril, 17% with perindopril, and the remaining with Fosinopril or Lisinopril. Median age at ACEi start was 11.2 (± 2.9). Our data suggest that cardiac atrophy is already present, before 10 years of age. ACEi seems to slow progression but not invert the process. [ABSTRACT FROM AUTHOR]

This article examines the occupational practices of four ambulant vendors (AVs) over a 20-day period, as they board, occupy, and alight trains to make a living in the popular economy. It captures for the first time some of the multimodal communicative practices they deploy to present an engaging sales pitch, attempt to convert passengers into prospects and sustain their livelihoods on the move. A multimodal pragmatics analysis of their sales pitch as video-recorded by the AVs reveals three clear stages marked by body motion in alignment with other bodily and verbal activities to capture the audience as they zero in on the product attributes. The article highlights the dexterity and professionalism of these workers in combining different modalities to augment their presence and chances of securing sales as they navigate the challenges of the unequal working conditions they inhabit as captured from a novel first-person perspective. • Multimodal pragmatics analysis of ambulant vendors' sales pitches on a trainline. • Combines language in use and action coordination to outline the sales pitch. • 263 videos recorded by ambulant vendors as part of a participatory research project. • Multimodal practices were found to be product- and space-contingent. • Shows vendors' professionalism and adroitness under unequal working conditions. [ABSTRACT FROM AUTHOR]

Acute otitis media (AOM) is the most common childhood disease leading to antibiotic use. More than 80% of children under three years of age experience at least one episode, and about one-third of these report significant recurrence of episodes. In recent years, several studies reported that normal nasopharyngeal flora inhibits growth of common otopathogens, suggesting that maintenance of an "adequate" nasopharyngeal flora might prevent occurrence of upper respiratory tract infections, including AOM. This study aims to determine whether five-month treatment with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray prevents recurrence of AOM and prescription of antibiotics in children with diagnosis of recurrent AOM. Observational prospective cohort study including children aged 1–6 years with diagnosis of recurrent AOM registered with 31 Italian family pediatricians. 81 children were enrolled in the study from September 2016 to the end of the five therapeutic cycles of the Streptococcus salivarius 24SMB and Streptococcus oralis 89a supplied 7 days each month for 5 consecutive months. For each treated child, one untreated control was randomly selected, 1:1 matched for gender, age, and follow-up. 158 children (79 treated and 70 untreated) were included into the analysis (mean age, 3.9 years; 47% female). Univariate analysis showed a statistically significant 34% (95% CI 1%–56%) reduction in number of AOM episodes in treated children compared with those not treated. Significantly fewer antibiotics were dispensed among treated children (24%, 95% CI 1%–41%). Our findings suggest that intermittent treatment of children with diagnosis of recurrent AOM with nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a for a period of five months might be effective in preventing antibiotic use associated with recurrent episodes of AOM. Additional larger studies to address this important clinical problem are recommended. [ABSTRACT FROM AUTHOR]

The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy. We collected data of DMD patients with end-stage cardiomyopathy implanted with LVAD in our center (group 1) and the ones in regular follow-up not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD HF (heart failure) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. During long-term follow-up all data were recorded including echocardiography, ECG examination, laboratory blood tests, and respiratory function. Survival was represented by Kaplan Meier analysis and compared by log rank. A total of 8 DMD patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸ whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After 1 year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) and significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank&lt0.001), with a 5-year increase in life expectancy. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of EF due to a significant ventricular unloading coupled with chronic therapy. LVAD improved outcomes in patients with LVAD when compared to those without. An integration of outpatient DMD HF clinic and patient-centered palliative care will most likely increase the quality of life and delivery of care for this population. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that imposes a long-term follow-up. The purpose of our pilot study is to evaluate the usefulness of the cardiopulmonary stress test (CPET) in the follow-up after MIS-C. All patients admitted for MIS-C in our hospital in the 12 months preceding the date of observation were considered for inclusion in the study. Pre-existing cardio-respiratory diseases and/or the lack of collaboration were the exclusion criteria. At enrolment, each subject passed a cardiological examination, rest ECG, echocardiogram, 24 h Holter-ECG, blood tests, and a CPET complete of spirometry. A total of 20 patients met the inclusion criteria (11.76 ± 3.29 years, 13 male). In contrast to the normality of all second-level investigations, CPET showed lower-than-expected peakVO2 and peak-oxygen-pulse values (50% of cases) and higher-than-expected VE/VCO2-slope values (95% of cases). A statistically significant inverse correlation was observed between P-reactive-protein values at admission and peakVO2/kg values (p = 0.034), uric acid values at admission, and peakVO2 (p = 0.011) or peak-oxygen-pulse expressed as a percentage of predicted (p = 0.021), NT-proBNP values at admission and peakVO2 expressed as a percentage of predicted (p = 0.046). After MIS-C (4–12 months) relevant anomalies can be observed at CPET, which can be a valuable tool in the follow-up after this condition. [ABSTRACT FROM AUTHOR]

Psychosocial support (PSS) to caregivers of HIV-infected infants on antiretroviral treatment (ART) is crucial to ensure ART adherence and sustained long-term viral suppression in children. A specific approach including tools to monitor and understand adherence behavior and risk factors that prevent optimal treatment compliance are urgently needed. This qualitative exploratory study, conducted in southern Mozambique, monitored the infants' viral response trajectories during 18 months follow-up, as a measure of adherence, reviewed the caregiver's PSS session notes and the answers to a study questionnaire, to analyze whether the standard PSS checklist applied to infants' caregivers can identify barriers influencing their adherence. Only 9 of 31 infants had sustained virologic response. Reported factors affecting adherence were: difficulties in drugs administration, shared responsibility to administer treatment; disclosure of child's HIV status to family members but lack of engagement; mother's ART interruption and poor viral response. In conclusion, we found that the standard PSS approach alone, applied to caregivers, was lacking focus on many relevant matters that were identified by the study questionnaire. A comprehensive patient-centered PSS package of care, including an adherence risk factor monitoring tool, tailored to caregivers and their children must be developed. [ABSTRACT FROM AUTHOR]

Background: A time-dependent analysis, usually by means of Poisson and Cox regression models, can be applied to prevent immortal time bias. However, the use of the Poisson model requires the assumption that the event rate is constant over time. This study aims to assess the potential consequences of using the Poisson model to cope with immortal time bias on estimating the exposure-outcome relationship in the case of time-varying risks. Methods: A simulation study was carried out. Survival times were assumed to follow a Weibull distribution, and the Weibull parameters were chosen to identify three different scenarios: the hazard of the event is constant, decreases, or increases over time. A dichotomous time-varying exposure in which patients can change at most once from unexposed to exposed was considered. The Poisson model was fitted to estimate the exposure-outcome association. Results: Small changes in the outcome risk over time (as denoted by the shape parameter of the Weibull distribution) strongly affected the exposure-outcome association estimate. The estimated effect of exposure was always lower and greater than the true exposure effect when the event risk decreases or increases over time, and this was the case irrespective of the true exposure effect. The bias magnitude was positively associated with the prevalence of and time to exposure. Conclusions: Biased estimates were obtained from the Poisson model to cope with immortal time. In settings with a time-varying outcome risk, the model should adjust for the trend in outcome risk. Otherwise, other models should be considered. [ABSTRACT FROM AUTHOR]

The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy (DMD-DCM). We collected data of end stage DMD-DCM patients who were implanted with LVAD in our center (group 1) and the ones in regular follow-up because not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD heart failure (HF) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. All data during long-term follow-up were recorded including echocardiography, ECG examination, laboratory blood tests, BNP dosing and assessment of nutritional status and respiratory function. Survival of the groups was represented by Kaplan Meier analysis and compared by log rank. A total of eight DMD-DCM patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The most prominent complications were bleeding and infections with one episode of acute heart failure that was successfully treated. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After one year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) together with a significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank<0.001), with a 5-year increase in life expectancy. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function. LVAD improved outcomes in patients with LVAD when compared to those without. [ABSTRACT FROM AUTHOR]

We aim to evaluate clinical outcomes, echocardiographic changes, heart rate (HR) modifications and side effects in children with dilated cardiomyopathy (DCM) and chronic heart failure (HF) treated by high dosage of carvedilol. We prospectively enrolled pediatric patients with DCM and ventricular dysfunction (EF <45%) referred to our institute. All enrolled patients were treated with high dosage of carvedilol coupled to heart failure therapy (ace inhibitors; diuretics, aldosterone blockade) in order to achieve a reduction of heart rate > 20% from baseline. Conventional treatment should be started from at least 1 month. Initial dosage of carvedilol was 0.1 mg/kg/day, up-titrated every 2 weeks to a maximum dose of 1 mg/kg/day. All data were compared to an historical control group treated with low dose of carvedilol or without beta-blockers. Data were collected before and after one year of maximum tolerated treatment. 65 patients (58% male) were enrolled, mean age was 13.4 +/- 9 years. 72 patients (48% male) were enrolled in the control group, mean age was 3.9 +/- 3.7. Mean duration of treatment was 50 months. HR reduction and EF improvement were statistically significant after treatment (mean HR reduction was 23%, p<0,0001; mean EF improvement 11,9%, p<0,0001); as well as decrease in LV diameters (p=0.001), volumes (p=0.029) and BNP levels (p=0.029) compared to control group. All patients survived, and 4 out of 4 were delisted from transplant list; on the contrary 32 patients of group 2 were transplanted and 11 died. Blood pressure remained stable for all patients treated with carvedilol and no side effects were recorded. High dosage of carvedilol up-titrated to achieve a reduction of heart rate of 20%, in addition to standard therapy, significantly improve ventricular function and survival in pediatric patients with DCM. [ABSTRACT FROM AUTHOR]

TAR DNA-binding protein 43 (TDP-43) forms intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. Its N-terminal domain (NTD) can dimerise/oligomerise with the head-to-tail arrangement, which is essential for function but also favours liquid-liquid phase separation and inclusion formation of full-length TDP-43. Using various biophysical approaches, we identified an alternative conformational state of NTD in the presence of Sulfobetaine 3-10 (SB3-10), with higher content of α-helical structure and tryptophan solvent exposure. NMR shows a highly mobile structure, with partially folded regions and β-sheet content decrease, with a concomitant increase of α-helical structure. It is monomeric and reverts to native oligomeric NTD upon SB3-10 dilution. The equilibrium GdnHCl-induced denaturation shows a cooperative folding and a somewhat lower conformational stability. When the aggregation processes were compared with and without pre-incubation with SB3-10, but at the identical final SB3-10 concentration, a slower aggregation was found in the former case, despite the reversible attainment of the native conformation in both cases. This was attributed to protein monomerization and oligomeric seeds disruption by the conditions promoting the alternative conformation. Overall, the results show a high plasticity of TDP-43 NTD and identify strategies to monomerise TDP-43 NTD for methodological and biomedical applications. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan. METHODS We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015. RESULTS Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7–20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant. CONCLUSIONS The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge. [ABSTRACT FROM AUTHOR]

Background: The interaction between proteins and nanoparticles is a very relevant subject because of the potential applications in medicine and material science in general. Further interest derives from the amyloidogenic character of the considered protein, β2-microglobulin (β2m), which may be regarded as a paradigmatic system for possible therapeutic strategies. Previous evidence showed in fact that gold nanoparticles (AuNPs) are able to inhibit β2m fibril formation in vitro. Methods: NMR (Nuclear Magnetic Resonance) and ESR (Electron Spin Resonance) spectroscopy are employed to characterize the paramagnetic perturbation of the extrinsic nitroxide probe Tempol on β2m in the absence and presence of AuNPs to determine the surface accessibility properties and the occurrence of chemical or conformational exchange, based on measurements conducted under magnetization equilibrium and non-equilibrium conditions. Results: The nitroxide perturbation analysis successfully identifies the protein regions where protein-protein or protein-AuNPs interactions hinder accessibility or/and establish exchange contacts. These information give interesting clues to recognize the fibrillation interface of β2m and hypothesize a mechanism for AuNPs fibrillogenesis inhibition. Conclusions: The presented approach can be advantageously applied to the characterization of the interface in protein-protein and protein-nanoparticles interactions. [ABSTRACT FROM AUTHOR]