Search

Body size is a major determinant of patient's dose during percutaneous coronary interventions (PCI). Body mass index, body surface area (BSA), lean body mass and weight are commonly used estimates for body size. We aim to identify which of these measures and which procedural/clinical characteristics can better predict received dose.Dose area product (DAP, GycmOverall 6623 PCI were analysed, median fluoroscopy DAP rate was 35 [IQR 2.7,4.4] GycmMain determinants of patient radiation dose are: BSA, female sex, height and number of treated vessels. In an era of increasing PCI complexity and obesity prevalence, these results can help clinicians tailoring X-ray administration to patient's size.

In the present report it is described the design, the manufacturing and the successful surgical implant of one of the first 3D custom titanium vertebra realized with Additive Manufacturing technique and its use for the spinal reconstruction after en-bloc resection for primary osteogenic sarcoma. Clinical case presentation and the design of the 3D custom titanium vertebra was reported. It was also described the complex procedures adopted to evaluate the retrieved device from the histological point of view, as a tumor relapse hit the patient, one year after the reconstruction procedure. The histological evaluation confirmed that the resection technique exerts an important role in promoting bone formation: vertebral body osteotomies favored the reconstruction procedure and maximized the contact area between host bone/vertebral prosthesis thus favoring the bone tissue penetration and device colonization. The sharing of these results is very important as they represent the starting point for improving the knowledge starting from the evidence obtained in a challenging clinical condition and with post-operative treatments that could be never reproduced in preclinical model.

Background The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature—lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4 nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)—were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model. Results The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect. Conclusions Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.

Aim: To investigate near infrared-induced phototoxicity toward lung cancer cells, and the biodegradability and effect on immune cells of glucose-derived carbon nanoparticles (CNPs). Methods: The human A549 lung adenocarcinoma cell line was used as a model to study the phototoxicity of CNPs. The biodegradability and the effect on immune cells was demonstrated in primary human neutrophils and macrophages. Results: Near infrared-activated CNPs elicited rapid cell death, characterized by the elevation of heat shock proteins and the induction of DNA damage. CNPs were found to be noncytotoxic toward primary human macrophages and were susceptible to biodegradation when cocultured with human neutrophils. Conclusions: Our results identify CNPs as promising platforms for photothermal therapy of lung cancer.

Pericardial effusion can dangerously precipitate patient’s hemodynamic stability and requires prompt intervention in case of tamponade. We investigated potential predictors of in-hospital mortality, a composite outcome of in-hospital mortality, pericardiocentesis-related complications, and the need for emergency cardiac surgery and all-cause mortality in patients undergoing percutaneous pericardiocentesis. This is an observational, retrospective, single-center study on patients undergoing percutaneous pericardiocentesis (2010–2019). We enrolled 81 consecutive patients. Median age was 71.4 years (interquartile range [IQR] 58.1–78.1 years) and 51 (63%) were male. Most of the pericardiocentesis were performed in an urgency setting (76.5%) for cardiac tamponade (77.8%). The most common etiology was idiopathic (33.3%) followed by neoplastic (22.2%). In-hospital mortality was 14.8% while mortality during follow-up (mean 17.1 months) was 44.4%. Only hemodynamic instability (i.e., cardiogenic shock, hypotension refractory to fluid challenge therapy and inotropes) was associated with in-hospital mortality at the univariate analysis (odds ratio [OR] 7.2; 95% confidence interval [CI] 1.76–29.4). Non-neoplastic/non-idiopathic etiology and hemodynamic instability were associated with the composite outcome of in-hospital mortality, need for emergency cardiac surgery, or pericardiocentesis-related complications (OR 5.75, 95% CI 1.65–20.01, and OR 5.81, 95% CI 2.11–15.97, respectively). Multivariate Cox regression analysis adjusted for possible confounding variables (age, coronary artery disease, and hemodynamic instability) showed that neoplastic etiology was independently associated with medium-term mortality (hazard ratio [HR] 4.05, 95% CI 1.45–11.36). In a real-world population treated with pericardiocentesis for pericardial effusion, in-hospital adverse outcomes and medium-term mortality are consistent, in particular for patients presenting with hemodynamic instability or neoplastic pericardial effusion.

Biomolecular corona formation has emerged as a recurring and important phenomenon in nanomedicine that has been investigated for potential applications in disease diagnosis. In this study, we have combined the "personalized protein corona" with the N-glycosylation profiling that has recently gained considerable interest in human plasma biomarker discovery as a powerful early warning diagnostic and patient stratification tool. We envisioned that the protein corona formation could be exploited as an enrichment step that is critically important in both proteomic and proteoglycomic workflows. By using silica nanoparticles, plasma fibrinogen was enriched to a level in which its proteomic and glycomic "fingerprints" could be traced with confidence. Despite being a more simplified glycan profile compared to full plasma, the corona glycan profile revealed a fibrinogen-derived glycan peak that was found to potentially distinguish lung cancer patients from controls in a pilot study.

Objectives Despite advances in understanding associations among attention‐deficit hyperactivity disorder (ADHD), emotion dysregulation (ED), and related outcomes, there is incongruity between ADHD‐relevant conceptualizations of ED and available measures of ED. To assess the psychometric properties of a parent‐report questionnaire of ED conceptualized as deficits in the ability to modulate the (a) speed/degree of emotion escalation; (b) expression intensity; and (c) speed/degree of de‐escalation. Methods Participants were 209 adolescents with ADHD (78% male; 13.5–17.8 years old [M = 15.2 SD = 0.91]). Questionnaire items were selected from parent‐report scales of ED and oppositional defiant disorder and subjected to exploratory factor analysis (EFA) and validity analyses. Results The EFA revealed two factors, with speed/degree of escalation combined with intensity as factor one, and speed/degree of de‐escalation as factor two. Factor one scores were related to ADHD impulsivity symptoms but not to anxiety and depression symptoms and they remained predictors of impulsivity even in the presence of self‐report ED, evincing convergent, discriminant, and incremental validity. Factor two scores were related to anxiety and depression but not impulsivity, evincing convergent and discriminant validity. Conclusion These results inform our understanding of ADHD‐relevant ED in adolescence and offer avenues for future research in measurement development, as well as for understanding ED and ADHD‐related impairment.

INTRODUCTION: A total ankle replacement in a jet pilot after an open, high-energy foot and ankle fracture and dislocation with talar extrusion in a plane crash was carefully evaluated before considering fitness to fly.CASE REPORT: A 33-yr-old male test pilot of the Italian Air Force was involved in a plane crash and reported an open high-energy fracture/dislocation of the right ankle, with the expulsion of the right talus due to the impact, and other fractures. A titanium replica was inserted inside the ankle. However, the patient suffered from intolerable pain and developed arthritic changes in the cartilage of the tibial plafond. For these reasons, a decision was made to perform a custom-made total ankle replacement.DISCUSSION: The 2-yr follow-up after the last operation and the evaluation of the pilot’s fitness to fly are reported in this case study. The pilot was assessed fit to fly, including high performance military aircrafts.Verde P, Guardigli S, Morgagni F, Roberts S, Monopoli D, Scala A. Total ankle replacement in a military jet pilot. Aerosp Med Hum Perform. 2020; 91(7):597–603.

BACKGROUND Aspirin is the cornerstone of the anti-platelet therapy during the acute phase of ST-segment elevation myocardial infarction (STEMI), and it can be administrated orally or intravenously. The oral loading dose of aspirin is well characterized, whereas there are little data on the optimal intravenous (IV) loading dose. AIM To confirm if the mortality of patients treated with a loading dose of IV aspirin was comparable to that of patients treated with the most usual aspirin per os. PATIENTS AND METHODS We analyzed the overall mortality during hospitalization and at 1 year follow-up among 756 consecutive patients with STEMI. Four hundred seventy-eight (63.2%) patients received per os and 278 (36.8%) IV aspirin. We divided the 278 patients of the IV aspirin group into two subgroups, based on the median value of the dose of aspirin used as a load. RESULTS The per os aspirin group took 234 ± 138 mg of aspirin per os at the first medical contact; the IV low-dose group 194 ± 87 mg, and the IV high-dose group 483 ± 194 mg of IV aspirin. No differences were observed in mortality rate after 1-year of follow-up. In-hospital mortality resulted significantly higher (9.3%) in the IV high-dose group respect to the IV low-dose one (5.0%) and per os aspirin group (6.0%) (P < 0.01 for both). CONCLUSION In this retrospective study, high dose IV aspirin loading in STEMI increased intra-hospital mortality. Further study is necessary to define the optimal dose of intravenous aspirin in STEMI.

Objective: Both qualitative and quantitative analyses were used to (a) describe the romantic and sexual relationships of adolescents with ADHD and (b) examine how ADHD-related impairments (e.g., social skill deficits and emotion dysregulation [ED]) are associated with romantic relationship outcomes in this group. Method: Adolescents with ADHD ( N = 171; 80% male; 70% White) responded to questions about their romantic and sexual relationship experiences and ED. Parents provided ratings of ADHD symptoms, ED, and social skills. Results: Adolescents with ADHD reported high rates of romantic relationship turnover and low rates of physical intimacy. More severe self-reported ED was associated with increased likelihood of engaging in romantic relationships, having more romantic relationship partners, increased likelihood of engaging in sexual intercourse, and increased likelihood of engaging in unprotected sex. Conclusion: Early intervention programs that alter the developmental trajectory of romantic relationships among individuals with ADHD may benefit from targeting ED among these youth.

The inequities caused by racism include negative impacts on health and quality of life. A key grant-making strategy of the CareQuest Institute for Oral Health has been the development of a network of stakeholders, the Oral Health Progress and Equity Network (OPEN), which engages and leverages community voices to address racism and the corresponding health inequities across the lifespan.OPEN's nearly 3000 members undertake various approaches to acknowledge and address the negative impact of systemic racism on health. OPEN has developed structures and offerings that have advanced a unique culture of equity, which encourages authentic dialogue. OPEN created and facilitated cohorts within the network called Network Response Teams to elevate awareness and develop strategies to address health disparities advocating for specific populations, including LGBTQIA+, Native American, LatinX, People with Disabilities, and rural residents, Medicare, and Medicaid. Network members work toward an equitable oral health system by aligning common goals.The activities and products of these teams and OPEN developed trusted relationships to combat the impacts of racism and promoted equitable oral health locally and nationally.Supporting network development is a highly effective tool to combat racism.

Aims Recently, the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial demonstrated that dual therapy reduced cardiovascular outcomes compared with aspirin alone in patients with stable atherosclerotic disease. Methods and results We sought to assess the proportion of patients eligible for the COMPASS trial and to compare the epidemiology and outcome of these patients with those without COMPASS inclusion or with any exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease. Among the 4068 patients with detailed information allowing evaluation of eligibility, 1416 (34.8%) did not fulfil the inclusion criteria (COMPASS-Not-Included), 841 (20.7%) had exclusion criteria (COMPASS-Excluded), and the remaining 1811 (44.5%) were classified as COMPASS-Like. At 1 year, the incidence of major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was 0.9% in the COMPASS-Not-Included and 2.0% in the COMPASS-Like (P = 0.01), and 5.0% in the COMPASS-Excluded group (P Conclusion In a contemporary real-world cohort registry of stable coronary artery disease, most patients resulted as eligible for the COMPASS. These patients presented a considerable annual risk of MACE that consistently increases in the presence of multiple risk factors.

Emotion dysregulation (ED) is a transdiagnostic risk factor for several forms of psychopathology. One established, integrative conceptualization of ED that has informed our understanding of psychopathology (Gratz & Roemer, 2004) was recently extended to account for state-level and specifically physiological aspects of ED. As such, the goal of the current study was to assess the degree to which this conceptualization could be captured using a physiological, state-level index (i.e., the late positive potential; LPP). Participants (N=41; M(age)=27.5 years, SD=11.0) completed a trait-based rating scale measure of the extended conceptualization of ED and viewed a series of images that ranged in valence (i.e., unpleasant, pleasant, and neutral). Multilevel modeling indicated some points of convergence between rating scale scores and the LPP, and other points of divergence. Findings underscore the utility of a multi-method approach to improve understanding of key transdiagnostic characteristics across levels of analysis. Further, results are novel evidence supporting validity of the extended conceptualization of ED.

Aims: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36months. Methods and results: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36months. No differences were observed in biomarker concentration between the two study arms, ‘prevention' vs. ‘troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36months was 23.4ng/L, higher (N.S.) than at baseline, 17.6ng/L. PTX3 peaked at 5.2ng/mL 1month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26ng/L 1month after CT and returned to 3ng/L until the last measurement at 36months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24mL/m2. Conclusions: First-in-life CT with median cumulative dose of anthracyclines of 180mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

Sézary syndrome (SS) is a rare and aggressive variant of cutaneous T-cell lymphoma. It is characterized by the copresence of CD4+ neoplastic lymphocytes, named Sezary cells, mainly in the blood, lymph nodes, and skin where they induce chronic inflammation that in turn impairs the patient's QOL and fuels neoplastic cells. SS is not readily cured, but immunotherapy is becoming an effective option for this lymphoma. In this study, we investigated, in a large cohort of patients with SS, the expression and function of the immune checkpoint molecule CD39, which degrades proinflammatory extracellular adenosine triphosphate. We showed that the SNP rs10748643 A/G within the ENTPD1 gene coding for the CD39 protein controls its expression level. Patients carrying the A/G‒G/G genotype showed a significantly higher frequency of clonal CD4+CD39+ SS cells than those carrying the A/A genotype. Different from other cancers, high CD39 expression correlates with a better prognosis. Comparing primary G/G with A/A lymphoma cells, we observed that G/G SS cells have a higher ability to degrade adenosine triphosphate, increased apoptotic susceptibility, and upon activation, reduced IL-2 production. Accordingly, CD39 enzymatic inhibition enhances SS cell viability and IL-2 production on activation. These results strongly suggest a special caution for SS treatment with therapeutic inhibitors of CD39.

Cutaneous T-cell lymphoma is a group of incurable extranodal non-Hodgkin lymphomas that develop from the skin-homing CD4+ T cell. Mycosis fungoides and Sézary syndrome are the most common histological subtypes. Although next-generation sequencing data provided significant advances in the comprehension of the genetic basis of this lymphoma, there is not uniform consensus on the identity and prevalence of putative driver genes for this heterogeneous group of tumors. Additional studies may increase the knowledge about the complex genetic etiology characterizing this lymphoma. We used SNP6 arrays and GISTIC algorithm to prioritize a list of focal somatic copy-number alterations in a dataset of multiple sequential samples from 21 Sézary syndrome patients. Our results confirmed a prevalence of significant focal deletions over amplifications: single well-known tumor suppressors, such as TP53, PTEN, and RB1, are targeted by these aberrations. In our cohort, ZEB1 (TCF8, ZFHX1A) spans a deletion having the highest level of significance. In a larger group of 43 patients, we found that ZEB1 is affected by deletions and somatic inactivating mutations in 46.5% of cases; also, we found potentially relevant ZEB1 germline variants. The survival analysis shows a worse clinical course for patients with ZEB1 biallelic inactivation. Multiple abnormal expression signatures were found associated with ZEB1 depletion in Sézary patients we verified that ZEB1 exerts a role in oxidative response of Sézary cells. Our data confirm the importance of deletions in the pathogenesis of cutaneous T-cell lymphoma. The characterization of ZEB1 abnormalities in Sézary syndrome fulfils the criteria of a canonical tumor suppressor gene. Although additional confirmations are needed, our findings suggest, for the first time, that ZEB1 germline variants might contribute to the risk of developing this disease. Also, we provide evidence that ZEB1 activity in Sézary cells, influencing the reactive oxygen species production, affects cell viability and apoptosis.

Sezary syndrome (SS) is a rare and aggressive variant of Cutaneous T-Cell Lymphoma characterized by neoplastic distribution mainly involving blood, skin, and lymph-node. Although a role of the skin microenvironment in SS pathogenesis has long been hypothesized, its function in vivo is poorly characterized. To deepen this aspect, here we compared skin to blood-derived SS cells concurrently obtained from SS patients highlighting a greater proliferation-index and a PI3K/AKT/mTORC1 pathway activation level, particularly of mTOR protein, in skin-derived-SS cells. We proved that SDF-1 and CCL21 chemokines, both overexpressed in SS tissues, induce mTORC1 signaling activation, cell proliferation and Ki67 up-regulation in a SS-derived cell line and primary-SS cells. In a cohort of 43 SS cases, we observed recurrent copy number variations (CNV) of members belonging to this cascade, namely: loss of LKB1 (48%), PTEN (39%) and PDCD4 (35%) and gains of P70S6K (30%). These alterations represent druggable targets unraveling new therapeutic treatments as metformin here evaluated in vitro. Moreover, CNV of PTEN, PDCD4, and P70S6K, evaluated individually or in combination, are associated with reduced survival of SS patients. These data shed light on effects in vivo of skin-SS cells interaction underlying the prognostic and therapeutic relevance of mTORC1 pathway in SS.

Terminal sialylation determines the plasma half-life of von Willebrand factor (VWF). A role for macrophage galactose lectin (MGL) in regulating hyposialylated VWF clearance has recently been proposed. In this study, we showed that MGL influences physiological plasma VWF clearance. MGL inhibition was associated with a significantly extended mean residence time and 3-fold increase in endogenous plasma VWF antigen levels (P

Portopulmonary hypertension (PoPH) is a clinical condition associated with end-stage liver disease, described by the coexistence of pulmonary arterial hypertension (PAH) and portal hypertension. In PoPH patients, there is a right ventricle (RV) remodeling to compensate for the increased resistance in the lung circulation. There are no studies on the effects of the PAH-targeted pharmacological treatment on the RV dimension and function. The present study summarizes our experience in patients with PoPH treated with sildenafil in a period of 6 years (from 2013 to 2019). We enrolled 64 consecutive patients identified as PoPH, all treated with sildenafil (57.6% in monotherapy; in the other cases in association with macitentan; in 19.0% with initial combination therapy). A hemodynamic invasive cardiopulmonary study was performed at baseline and after 6 months of sildenafil treatment. In our population we showed a significative improvement in RV performance, with a significant increase in RV stroke volume (+33%), RV ejection fraction (+31%) and RV stroke work index (+17.5%). We registered the reduction of the RV cavity dimension over time in all patients treated with sildenafil (RV end diastolic diameter decreased by 15% after 6 months of follow-up). Regarding diastolic function, we highlighted a very significant reduction in RV end-diastolic pressure (-50% concerning baseline). Sildenafil was effective both when used as monotherapy and in combination with macitentan. In conclusion, Sildenafil had a positive impact on RV systolic and diastolic function in patients with PoPH and was able to conditionate the reverse remodeling of the RV.

Underweight or overweight patients with cardiovascular diseases are associated with different outcomes. However, the data on the relation between body mass index (BMI) and outcomes after transcatheter aortic valve implantation (TAVI) are not homogeneous. The aim of this study was to assess the role of low BMI on short and long-term mortality in real-world patients undergoing TAVI. We retrospectively included patients undergoing TAVI for severe aortic valve stenosis. Patients were classified into three BMI categories: underweight (

Aims We evaluated the 1-year clinical events, pharmacological management, and quality of life in a contemporary cohort of stable coronary artery disease (CAD) patients managed by cardiologists. Methods and results START (STable Coronary Artery Diseases RegisTry) was a prospective, observational, nationwide study that enrolled 5070 stable CAD patients over 3 months in 183 cardiology centres in Italy. At 1 year, 4790 (94.5%) patients had data on vital status. Death occurred in 107 (2.2%) patients and the cause of death was cardiovascular in 41 (38.3%) of cases. Among the 4775 patients with follow-up data on clinical events available, a hospitalization due to cardiovascular and non-cardiovascular causes occurred in 523 (11.0%) and in 231 (4.8%) of cases, respectively. Over 60% of patients reported as ‘no problems’ in all domains (61.4–84.5%) of the EuroQoL quality of life 5D-5L questionnaire. Among the 3239 patients with clinical visit/telephone interview at follow-up, in whom optimal medical therapy (OMT; aspirin or thienopyridine, β-blocker, and statin) was prescribed at enrolment, 2971 (91.7%) were still receiving OMT at follow-up. At multivariable analysis, only increasing age (odds ratio 0.98; 95% confidence interval 0.97–0.99; P = 0.04) resulted as independent negative predictor of OMT persistence at 1 year from enrolment. Conclusion In this large, contemporary registry, stable CAD patients managed by cardiologists presented a high rate of clinical events at 1 year. Nevertheless, the persistence to OMT and quality of life appeared reasonable.

There is an urgent need for safe and effective approaches to combat COVID-19. Here, we asked whether lessons learned from nanotoxicology and nanomedicine could shed light on the current pandemic. SARS-CoV-2, the causative agent, may trigger a mild, self-limiting disease with respiratory symptoms, but patients may also succumb to a life-threatening systemic disease. The host response to the virus is equally complex and studies are now beginning to unravel the immunological correlates of COVID-19. Nanotechnology can be applied for the delivery of antiviral drugs or other repurposed drugs. Moreover, recent work has shown that synthetic nanoparticles wrapped with host-derived cellular membranes may prevent virus infection. We posit that nanoparticles decorated with ACE2, the receptor for SARS-CoV-2, could be exploited as decoys to intercept the virus before it infects cells in the respiratory tract. However, close attention should be paid to biocompatibility before such nano-decoys are deployed in the clinic.

Background The causes of preterm birth are multi-dimensional, including delayed and inadequate prenatal services as well as other medical and socioeconomic factors. This study aimed to examine the different levels of association between preterm birth and major medical co-morbidities among various racial/ethnic women enrolled in Medicaid. Methods This is a retrospective analysis of 457,200 women aged between 15 and 44 with a single live birth from the IBM® MarketScan® Multi-State Medicaid Database from 2014 to 2015. Preterm birth, defined by delivery before 37 completed weeks of gestation, was the primary dependent variable. All births were dichotomously categorized as either preterm or full-term birth using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Independent variables included race/ethnicity, categorized as non-Hispanic white, non-Hispanic black, Hispanic, or other. Medical co-morbidities included smoking, drug dependence, alcohol dependence, diabetes, and hypertension. Total healthy prenatal visit count and high-risk prenatal visit encounters identified during 30 weeks prior to the delivery date were included in the analysis. Results A significantly higher preterm birth rate was found in black women after controlled for medical co-morbidities, age, prenatal visit count, and high-risk pregnancy. Different levels of association between preterm birth outcome and major medical co-morbidities were examined among various racial/ethnic women enrolled in Medicaid. Drug dependence was associated with higher odds of preterm birth in black (OR = 2.56, 95% CI [1.92–3.41]) and white women (OR = 2.12, 95% CI [1.91–2.34]), when controlled for other variables. In Hispanic women, diabetes (OR=1.44, 95% CI [1.27, 1.64]) and hypertension (OR=1.98, 95% CI [1.74, 2.26]) were associated with higher odds of preterm birth. White women diagnosed with drug dependence had a 14.0% predicted probability of preterm birth, whereas black women diagnosed with drug dependence had a predicted probability of preterm birth of 21.5%. Conclusions The associations of medical co-morbidities and preterm births varied across racial and ethnic groups of women enrolled in Medicaid. This report calls for future research on racial/ethnic disparity in preterm birth to apply integrative and qualitative approaches to understand the disparity from a contextual perspective, especially for vulnerable pregnant women like Medicaid enrollees.

Hospital-based violence intervention programs (HVIPs) engage individuals who have experienced violent victimization in postmedical care programming, with the goal of reducing the incidence and impact of future injuries. Although there is some empirical support for HVIPs’ impact on violence and crime-related outcomes, proper impact assessment is limited by a lack of systematized research on outcomes that relate to the proximal goals and activities of the programs themselves. To address this critical gap, we conducted a two-stage Delphi method to elicit and prioritize these outcomes using the wisdom and experience of those who are engaged in service delivery (i.e., HVIP community-based practitioners, program coordinators, and embedded researchers; N = 79). Through this process, respondents prioritized outcomes related to posttraumatic stress symptoms, beliefs about aggression, coping strategies, and emotional regulation, which have not been consistently measured using validated or standardized tools. Results suggest that, rather than limiting program outcomes to those related to repeat violent injury or criminality, hospital- and community-based violence prevention programs seek to improve and measure mental health and socioemotional outcomes as a benchmark for healing and recovery after a violent injury. Prioritization of these outcomes broadens the definition of recovery to include psychosocial health and well-being. In addition, inclusion of these outcomes in effectiveness studies will serve to bolster the relevance of findings, and provide support for continued development and refinement of HVIP practice.

Progress in oligonucleotide chemistry has produced a shift in the nature of siRNA used, from formulated, minimally modified siRNAs, to unformulated, heavily modified siRNA conjugates. The introduction of extensive chemical modifications is essential for conjugate-mediated delivery. Modifications have a significant impact on siRNA efficacy through interference with recognition and processing by RNAi enzymatic machinery, severely restricting the sequence space available for siRNA design. Many algorithms available publicly can successfully predict the activity of non-modified siRNAs, but the efficiency of the algorithms for designing heavily modified siRNAs has never been systematically evaluated experimentally. Here we screened 356 cholesterol-conjugated siRNAs with extensive modifications and developed a linear regression-based algorithm that effectively predicts siRNA activity using two independent datasets. We further demonstrate that predictive determinants for modified and non-modified siRNAs differ substantially. The algorithm developed from the non-modified siRNAs dataset has no predictive power for modified siRNAs and vice versa. In the context of heavily modified siRNAs, the introduction of chemical asymmetry fully eliminates the requirement for thermodynamic bias, the major determinant for non-modified siRNA efficacy. Finally, we demonstrate that in addition to the sequence of the target site, the accessibility of the neighboring 3′ region significantly contributes to siRNA efficacy.

The recognition of the biological, diagnostic and medical importance of exosomes has given rise to an urgent need for efficient labelling of these extracellular vesicles in ways that do not alter their inherent characteristics. We report for the first time an endogenous method to NIR-fluorescent labelled exosomes using an amphiphilic probe without the need for immunolabelling or synthetic or chromatographic manipulation of exosomes. Comparative analyses of labelled and unlabelled exosomes with NTA, AFM, flow cytometry and immunoblot analysis all show a high degree of similarity. Spectroscopic analysis and fluorescence imaging confirmed the ability to visualise purified NIR-exosomes.

Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c)T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pTConclusion Neoadjuvant pembrolizumab resulted in 42% of patients with pT0 and was safely administered in patients with MIBC. This study indicates that pembrolizumab could be a worthwhile neoadjuvant therapy for the treatment of MIBC when limited to patients with PD-L1–positive or high-TMB tumors.

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical–chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were toxic in all cell types. TiO2 and SiO2 MNMs also triggered toxicity in some, but not all, cell types and the cell type-specific effects were influenced by the specific coating and surface modification. CeO2 MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type-specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.

The aim of our study was to develop and compare the biological performance of two types of biodegradable SN-38 loaded nanoparticles (NPs) with various surface properties, composed of low and high Mw triblock PLGA-PEG-PLGA copolymers, applying rational quality and safety by design approach. Therefore, along with the optimization of crucial physico-chemical properties and in order to evaluate the therapeutical potential and biocompatibility of prepared polymeric nanoparticles, analysis of nano-bio interactions, cell internalization, gene expression and biodistribution studies were performed. The optimized formulations, one of low Mw and one composed of high Mw PLGA-PEG-PLGA copolymer, exhibited different characteristics in terms of surface properties, particle size, zeta potential, drug loading, protein adsorption and biodistribution, which may be attributed to the variations in nano–bio interface interactions due to different NP building blocks length and Mw. On the contrary to protein adsorption and biodistribution studies, both types of NPs exhibited similar results during cell internalization and gene expression studies performed in cell culture medium containing serum proteins. This pool of useful data for internalization and efficacy as well as the notable advance in the circulation time of low Mw NPs may be further employed for shaping the potential of the designed nanocarriers.

A comprehensive assessment of the fetal brain is among the most difficult tasks of antenatal ultrasound. A specific expertise is required to obtain in particular the non-axial planes of the fetal head and to assess the sonographic appearance of the cerebral structures at different gestational ages in order to rule out the presence of intracranial anomalies (1). Multiplanar neurosonography is far more sensitive than the standard axial approach in the antenatal detection of fetal brain malformations and it is recommended in cases at high risk for CNS anomalies (2,3).

The phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway is hyperactivated in many tumors, as well as in cutaneous T-cell lymphoma (CTCL), which includes the mycosis fungoides and the aggressive variant known as Sezary syndrome (SS). TORC1 signaling is activated in SS cells by cytokines and chemokines, which are overexpressed in SS tissues. Furthermore, the recurrent copy number variation of genes belonging to this cascade, such as PTEN, LKB1, and P70S6K, contributes to the hyperactivation of the pathway. The aim of this study was to investigate the therapeutic potential of mTOR inhibitors in CTCL. We compared the efficacy of three rapalogs (rapamycin, temsirolimus, and everolimus) and the dual-mTOR/PI3K inhibitor PF-04691502 (hereinafter PF-502) in four CTCL cell lines. PF-502 was revealed to be the most effective inhibitor of cell growth. Interestingly, PF-502 also exerted its antitumor activity in patient-derived CTCL cells and in a xenograft mouse model, where it induced significant apoptosis and increased survival of treated mice. Furthermore, we found an inverse correlation between PTEN gene expression and the ability of PF-502 to induce apoptosis in SS cells. Our data strongly support the therapeutic potential of dual PI3K/mTOR inhibitors in CTCL.

Electron beam melting (EBM) was used to fabricate porous titanium alloy structures. The elastic modulus of these porous structures was similar to the elastic modulus of the cancellous human bone. Two types of cellular lattice structures were manufactured and tested: gyroids and diamonds. The design of the gyroid structures was determined by the main angle of the struts with respect to the axial direction. Thus, structures with angles of between 19 and 68.5° were manufactured. The aim of the design was to reduce the amount of material needed to fabricate a structure with the desired angles to increase the range of stiffness of the scaffolds. Compression tests were conducted to obtain the elastic modulus and the strength. Both parameters increased as the angle decreased. Finally, the specific strength of the gyroid structures was compared with that of the diamond structures and other types of structures. It is shown that, for angles lower than 35°, the gyroid structures had a high strength to weight ratios.

When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles.Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics.

There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.

Background To achieve optimal health and oral health, the system of care must place a person and their social well-being at the center of decision making and understand factors spent outside the clinical settings, including individual behavior, context and lifestyle. Main text Person-centered care offers a unique and compelling opportunity for dentistry, and its practitioners, to improve quality of care and overall health outcomes. For decades, the dominant treatment modalities within dentistry primarily focused on a surgical, treatment-oriented approach as opposed to health promotion and improvement. However, new business and care models are disrupting the dental care system, and transforming it into one that is focused on disease management and prevention-oriented primary care that considers overall health and well-being. We proposed a person-centered care model to improve oral health as an integral part of overall health. The model identified three key players who act as change agents with their respective roles and responsibilities: Person, provider, and health care system designer. Conclusions While previous person-centered models in dentistry focused on the role of providers within the clinical setting, this work emphasizes the role of the care designer in creating an environment where both person and provider are able to communicate effectively and achieve improved health outcomes.

Exogenous intravenous (IV) adenosine and epoprostenol are effective vasodilator agents, causing a substantial reduction in pulmonary vascular resistance in patients affected by idiopathic pulmonary arteriolar hypertension (PAH). Their action, in patients with PAH associated with other pathological conditions, is not well defined. In the present paper the authors retrospectively analyzed the acute hemodynamic effects of intravenous adenosine and epoprostenol in 30 consecutive patients (mean age: 58 ± 15 years; 21 females, and 9 males) affected by PAH associated with other pathological conditions, as determined by changes from baseline in systemic and pulmonary hemodynamic parameters. Acute IV administration of adenosine decreased pulmonary vascular resistance index (PVRI) by 3 Wood U/m2 (- 20%) compared to baseline (p = 0.02). We noted a slight, not significant, decrease in mean pulmonary artery pressure (mPAP) of 4 mmHg. Cardiac index (CI) increased by 0.5 L/min/m2 (15% increase respect to baseline; p = 0.03). The heart rate and mean systemic blood pressure (BP) did not change significantly. Acute IV administration of epoprostenol decreased PVRI by 6 mmHg (- 40%) respect to baseline (p Our results indicates that, in patients with PAH associated with other pathological conditions, adenosine is predominantly a positive inotropic agent; and epoprostenol a potent vasodilator of both pulmonary and systemic vessels, and a strong positive inotropic agent.

PurposeWear of ceramic orthopedic devices generates nanoparticles in vivo that may present a different biological character from the monolithic ceramic from which they are formed. The current work investigated protein adsorption from human plasma on alumina nanoparticles and monolithic samples representative of both wear particles and the ceramic components as implanted.Materials and MethodsA physicochemical characterization of the particles and their dispersion state was carried out, and the protein adsorption profiles were analyzed using 1D SDS-PAGE and mass spectrometry.ResultsSignificant differences in protein-binding profiles were identified where the nanoparticles selectively bound known transporter proteins rather than the more highly abundant serum proteins that were observed on the monoliths.ConclusionsProteins associated with opsonization of particles were seen to be present in the protein corona of the nanoparticles, which raises questions regarding the role of wear particles in periprosthetic tissue inflammation and aseptic loosening.

The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle-cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle-cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle-cell interactions by modulating the protein corona properties.

Nanoparticles in physiological environments are known to selectively adsorb proteins and other biomolecules forming a tightly bound biomolecular 'corona' on their surface. Where the exchange times of the proteins are sufficiently long, it is believed that the protein corona constitutes the particle identity in biological milieu. Here we show that proteins in the corona retain their functional characteristics and can specifically bind to cognate proteins on arrays of thousands of immobilised human proteins. The biological identity of the nanomaterial is seen to be specific to the blood plasma concentration in which they are exposed. We show that the resulting in situ nanoparticle interactome is dependent on the protein concentration in plasma, with the emergence of a small number of dominant protein-protein interactions. These interactions are those driven by proteins that are adsorbed onto the particle surface and whose binding epitopes are subsequently expressed or presented suitably on the particle surface. We suggest that, since specific tailored protein arrays for target systems and organs can be designed, their use may be an important element in an overall study of the biomolecular corona.

Nanoparticles (NPs) in contact with biological fluids become covered by a tightly bound layer of proteins, the “protein corona”, and it is largely accepted that this corona gives a new identity to NPs in biological milieu. We here consider the exposing scenario of NPs through an environmental route exemplified by the use of hydrophobins, highly adhesive proteins that are secreted into the environment in large quantities by fungi. HFBII of Trichoderma reesei has been used as a model protein and we have shown strong binding to polystyrene NPs of different sizes and surface groups. Hydrophobin coated NPs are shown to strongly increase the stability and the dispersion when exposed to human plasma compared to pristine ones particles. It is also shown that the presence of hydrophobin on the NPs results in an attenuated protein corona formation, in a different corona composition, and we also show that hydrophobin remained strongly associated to the NPs in competition with plasma proteins. As a conclusion we therefore suggest that the route of exposure of nanoparticles strongly affects their surface properties and their possible physiological behavior. Significance This work shows how a self-assembling protein, class II hydrophobin HFBII, with interesting biocompatible coating properties, strongly adsorbs on polystyrene NPs. HFBII is also shown to reduce aggregation of the NPs in human plasma which can increase their bioavailability with potential use in biomedical applications. The results here are also of significance for understanding possible interactions of NPs with living organisms. Hydrophobins are secreted in large quantities into the environment by fungi and this work shows how the biological environment of NPs determines the surface and colloidal properties of the particles by forming a protein corona, and that the history of the particle environment, here simulated with hydrophobin exposure, affects both plasma protein corona formation and dispersion behavior. This work thus simulates how alternative exposure routes affect nanoparticle properties, important in understanding the biological fate of NPs.

With 10,000 baby boomers turning 65 every day, many will be on fixed incomes and will lose dental insurance upon retirement. This article presents why a dental benefit in Medicare might save the US government money, and who would likely benefit. It details an approach to estimating costs of inclusion of a dental benefit in Medicare, and compares the proposed approach to existing proposals. Additionally, the ensuing steps needed to advance the conversation to include oral health in healthcare for the aged will be discussed.

Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLF). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of α1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.

Nanoparticles (NP), when exposed to biological fluids, are coated by specific proteins that form the so-called protein corona. While some adsorbing proteins exchange with the surroundings on a short time scale, described as a "dynamic" corona, others with higher affinity and long-lived interaction with the NP surface form a "hard" corona (HC), which is believed to mediate NP interaction with cellular machineries. In-depth NP protein corona characterization is therefore a necessary step in understanding the relationship between surface layer structure and biological outcomes. In the present work, we evaluate the protein composition and stability over time and we systematically challenge the formed complexes with surfactants. Each challenge is characterized through different physicochemical measurements (dynamic light scattering, ζ-potential, and differential centrifugal sedimentation) alongside proteomic evaluation in titration type experiments (surfactant titration). 100 nm silicon oxide (Si) and 100 nm carboxylated polystyrene (PS-COOH) NPs cloaked by human plasma HC were titrated with 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS, zwitterionic), Triton X-100 (nonionic), sodium dodecyl sulfate (SDS, anionic), and dodecyltrimethylammonium bromide (DTAB, cationic) surfactants. Composition and density of HC together with size and ζ-potential of NP-HC complexes were tracked at each step after surfactant titration. Results on Si NP-HC complexes showed that SDS removes most of the HC, while DTAB induces NP agglomeration. Analogous results were obtained for PS NP-HC complexes. Interestingly, CHAPS and Triton X-100, thanks to similar surface binding preferences, enable selective extraction of apolipoprotein AI (ApoAI) from Si NP hard coronas, leaving unaltered the dispersion physicochemical properties. These findings indicate that surfactant titration can enable the study of NP-HC stability through surfactant variation and also selective separation of certain proteins from the HC. This approach thus has an immediate analytical value as well as potential applications in HC engineering.

Urban ethnic minority youth are often exposed to high levels of aggression and violence. As such, many aggression intervention programs that have been designed with suburban nonethnic minority youth have been used or slightly adapted in order to try and meet the needs of high-risk urban youth. The current study contributes to the literature base by examining how well a range of social–cognitive, emotional distress and victimization, and prosocial factors are related to youth aggression in a sample of urban youth. This study utilized data gathered from 109 9- to 15-year-old youth (36.7% male; 84.4% African American) and their parents or caregivers. A series of hierarchical multiple regressions were fit predicting youth aggression from social–cognitive variables, victimization and distress, and prosocial variables, controlling for youth gender and age. Each set of variables explained a significant and unique amount of the variance in youth aggressive behavior. The full model including all predictors accounted for 41% of the variance in aggression. Models suggest that youth with stronger beliefs supportive of violence, youth who experience more overt victimization, and youth who experience greater distress in overtly aggressive situations are likely to be more aggressive. In contrast, youth with higher self-esteem and youth who endorse greater leadership efficacy are likely to be less aggressive. Contrary to hypotheses, hostile attributional bias and knowledge of social information processing, experience of relational victimization, distress in relationally aggressive situations, and community engagement were not associated with aggression. Our study is one of the first to address these important questions for low-income, predominately ethnic minority urban youth, and it has clear implications for adapting aggression prevention programs to be culturally sensitive for urban African American youth.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer's, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of Aβ in aqueous solution. A size and surface area dependent "dual" effect on Aβ fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of Aβ fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation.

Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases1, 2. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona3, 4 can ‘screen’ the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting. Author has checked copyright AMS

The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future. TS 11.09.13

AIMS The clinical features of the adult population with congenital heart disease (CHD) are still not well characterized, particularly in the subset with more severe lesions. We report the data collected in the National Association of Hospital Cardiologists Toscana grown-up CHD (GUCH) registry over its first 8-month enrolment period. METHODS The Registry included consecutive patients aged more than 16 years with a documented diagnosis of CHD, enrolled in seven different Tuscan hospitals using a web-based electronic form. Severe CHD was defined as cyanotic CHD, or acyanotic lesion with significant haemodynamic impact requiring surgical and/or percutaneous correction. RESULTS Between November 2009 and June 2010 a total of 1641 patients (mean age 41.8 ± 19.3 years, 52.2% women) were enrolled. Atrial septal defect was the most common lesion, accounting for more than one-third of cases. Atrial and ventricular septal defects together accounted for about half of all CHDs. Nearly one-third of patients had New York Heart Association (NYHA) class 2 or more. A history of recurrent arrhythmias was reported in 15% of cases, and 12% of patients were on oral anticoagulants at the time of enrolment. The prevalence of pulmonary hypertension was 6%, and the prevalence of Eisenmenger syndrome was 1.2%. Severe CHD was present in 42% of patients. Younger age, higher NYHA class, male sex, and the need for oral anticoagulants were the only independent predictors of severe CHD. CONCLUSION Information about the clinical characteristics and the CHD type distribution of a sample of Tuscan GUCH population was provided. Severe CHD accounts for about 40% of all CHDs in this population. CHD severity is associated with younger age, male gender, worse NYHA class, and need for oral anticoagulation.

Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging. Due to their buoyancy, the commonly available approaches to study their behaviour in complex media are not easily applicable and their use in modern medicine requires such behaviour to be fully elucidated. Here we have used for the first time flow cytometry as a new high throughput approach that allows characterisation of the MB dispersion, prior to and after exposure in different biological media and we have additionally developed a method that allows characterisation of the strongly bound proteins adsorbed on the MBs, to fully predict their biological behaviour in biological milieu.