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Erdheim-Chester disease (ECD) is a rare clonal myeloid neoplasm typically affecting adults over 50 years old, with bone lesions in almost all patients. The prognosis is poor in most cases if left untreated. Clinical manifestations are not specific, which hinders early diagnosis. The disease has distinct radiological features. However, three-phase bone scintigraphy exhibits the most typical pattern of all imaging modalities, which is the prominent strikingly symmetrical radiotracer uptake in the distal ends of the femurs and proximal and distal ends of the tibiae, sparing the epiphyses. We report a case of a 54-year-old female patient, presenting with atypical persistent knee joint pain. After an MRI scan, she underwent a three-phase bone scan, revealing the characteristic pattern, thus indicating a possible ECD diagnosis, which was eventually confirmed in biopsy material. Novel aspects of the pathophysiology and treatment of the disease, as well as a differential diagnosis from the perspective of an MSK radiologist and nuclear medicine physician, are also discussed. [ABSTRACT FROM AUTHOR]

Aims: To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension. Methods: Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. Results: In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = − 6.01 mmHg; 95% CI = [− 7.46, − 4.55] and MD = − 5.01 mmHg; 95% CI = [− 5.91, − 4.11], respectively). Moreover, resulted a similar reduction in systolic BP (MD = − 0.22 mmHg; 95% CI = [− 0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to the active comparator (MD = − 0.71 mmHg; 95% CI = [− 1.27, − 0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP. Conclusion: Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction. [ABSTRACT FROM AUTHOR]

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. Summary: The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed. [ABSTRACT FROM AUTHOR]

This explorative literature review aims to examine the content and methodologies of recent empirical studies on the aspirations of youth in situations of migration in Europe. The search yielded 30 peer-reviewed social science publications in English for the period 2010–2022, including both intra-European migrants ages 10–24 and youth with backgrounds from outside Europe. Contextual analysis was used to analyse the content of the reviewed studies, while a typology developed by Beckert and Suckert was used to examine features of the future appearing in the studies' research aims, methodology and findings. The analysis broadly situated the studies within constructivist traditions, occupying a mid-position between deterministic and agency-oriented epistemologies. All the features of the future listed by Beckert and Suckert were found in the material, but the categories 'Temporal configurations of the future' and 'Space of the future' showed greater complexities. Participants in the studies lived in different European countries and the study samples comprised a wide range of ages, socioeconomic backgrounds, and status of residence. Nevertheless, barriers linked to participants' position as migrants were tangible, while the ability these young people had to envisage the future was strongly affected by uncertainties linked to migration policy and administrative decisions on their status. A mismatch could notably be observed between youth aspirations and the opportunities offered by their life situation, which led to delays in life projects and the inability to plan ahead. Critical relevance statement By an analysis of social studies research on aspirations of youth in situations of migration in various European countries, this review highlights the need to consider implications for youth aspirations and life trajectories in both policy and practice Key points • Young people in situations of migration have high aspirations but confront substantial barriers • Uncertainties prevent youth from long-term planning and realising life projects • Current policies create conditions that are not consistent with European values and ambitions [ABSTRACT FROM AUTHOR]

Previous research indicates narcissism can aid stress management. Nonetheless, its common perception and dissemination as socially aversive may hamper its acknowledgment and use as an asset in the context of stress. This experimental study investigated the effects of receiving positive or negative information (i.e., prompts) about narcissism in the context of stress on attitudes towards this trait's association with stress. It also assessed individuals' experiences of narcissism's stress-coping properties when one believes themselves to be a high narcissism scorer, via an online survey. Hundred and five adults ( M age = 32.0; 22–64 years) completed measures of state-stress, music preferences, and narcissism. They were then randomly assigned to either the positive or negative prompt groups, being shown information highlighting the positive or negative impact of narcissism on stress management, respectively. Participants were then informed they scored above average on narcissism, despite their actual questionnaire scores, and undertook a stress-inducing procedure. Self-reported stress, implicit and explicit attitudes were measured pre- and post-prompt presentation. Results showed that, while prompts did not influence attitudes nor stress outcomes, individuals displayed neutral implicit attitudes towards narcissism's association with stress across measurement timepoints. These findings suggest that people's attitudes towards narcissism in the context of stress have not been deteriorated by this trait's predominant negative depiction outside this context. Therefore, the dissemination and establishment of narcissism as an asset for stress-coping may be received by the general population with less resistance than anticipated. [ABSTRACT FROM AUTHOR]

During the last decade, the landscape of type 2 diabetes (T2D) management has been completely transformed, moving from a glucose-centric perspective to a holistic approach that also takes into account weight control and organ protection. Dipeptidyl peptidase-4 inhibitors (DPP4i) are oral agents that have been used for the treatment of T2D for almost 20 years. Although they present an excellent safety profile, including the risk of hypoglycemia, they lack the spectacular cardiorenal benefits and weight-loss effects of the newer antidiabetic agents. This poses the question of whether they still deserve a place in the arsenal of drugs against T2D. In this article, we use a hypothetical case scenario to illustrate possible patient profiles where DPP4i could prove useful in the clinical setting. We discuss the advantages and disadvantages of the category, focusing on glycemic control, weight management, and cardiorenal protection, which are the pillars of modern T2D management, also considering its safety profile and cost-effectiveness. We conclude that in most cases, DPP4i present a more favorable risk–benefit ratio compared to sulfonylureas, which are still widely prescribed throughout the world. We also suggest that future research should clarify the reasons behind the contradictory findings between human and animal studies on cardiorenal effects of the class and identify subgroups of patients who would derive most benefit with DPP4i treatment. [ABSTRACT FROM AUTHOR]

Bullying is a significant problem in the USA, with both school bullying and cyberbullying peaking in middle school. Although 80% of students witness bullying, only half of middle school students report bullying to their teachers. Bystander training is effective in teaching students how to intervene; however, teachers play an instrumental role in shaping bystander behavior. The purpose of this qualitative study was to understand the perspectives of middle school personnel on the content, usefulness, relevance, and feasibility of a teacher training designed as a companion module to a brief, bullying bystander intervention (STAC). School personnel (N = 15) recruited from two schools participated in focus groups to provide feedback on the STAC Teacher Module. Thematic analyses elicited eight key themes. Participants provided specific feedback on ways the program could be improved, including providing more information about cyberbullying. Overall, participants liked the content of the training, but shared they would like built-in discussion time. Participants also indicated the program was useful, relevant, and feasible for middle schools in their communities. Participants indicated their current school offerings are limited and that there is a need for bullying-specific training. Participants also identified implementation challenges, including limited time and financial resources, as well as the need for teacher buy-in. Finally, participants reported liking the flexibility of a technology-based program, but expressed concerns that it would be harder to engage teachers in an online format. This study serves as a first step in developing the STAC Teacher Module for middle schools. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) — a biomarker of atherosclerosis — and assessments of macrovascular endothelial function in patients with SSc. Methods: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). Results: Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc. Conclusions: The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc. [ABSTRACT FROM AUTHOR]

Examining factors that protect against the negative repercussions of stress on everyday functioning is paramount. This experimental study investigated the effects of music listening and personality on the reduction of perceived stress and cognitive performance. Seventy adults (18–45 years, M = 22.8, SD = 6.6) completed measures of the Dark Triad traits (psychopathy, narcissism, and Machiavellianism), music preferences, and music uses, and undertook a stress-inducing procedure. Participants were randomly allocated to three groups: hip-hop/rap, classical music, control, being exposed to the respective genre or silence for 20 min after the predicted peak in stress. Results showed that classical and hip-hop/rap music equally facilitated stress reduction. Narcissism predicted lower stress when classical music preference was high. Narcissism also predicted enhanced performance but also greater stress, when paired with infrequent stress-management through music. These novel findings demonstrate how particular genres and traits, despite being predominantly negatively perceived, can enhance stress reduction or cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). We sought to determine whether sodium-glucose co-transporter-2 (SGLT-2) inhibitors affect indices of CAN in patients with T2DM. Methods: We searched for parallel group or cross-over randomized controlled trials (RCTs) enrolling adult subjects with T2DM, assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on CAN. PubMed, Cochrane Library and gray literature sources were searched. We set as primary efficacy outcome the change in the low-frequency-to-high-frequency (LF/HF) ratio. We set as secondary efficacy outcomes: first, the change in the standard deviation of all 5 min mean normal RR intervals and second, the change in the square root of the mean of the sum of the squares of differences between adjacent RR intervals (r-MSSD). Protocol has not been registered at a publicly available repository. Results: We pooled data from four RCTs in a total of 247 subjects with T2DM. SGLT-2 inhibitor treatment did not have a significant effect on LF/HF ratio (MD = − 0.11, 95% CI − 0.35 to 0.12, I2 = 0%, p = 0.36). SGLT-2 inhibitor treatment did not have a significant impact either on SDNN (MD = − 2.83, 95% CI − 7.41 to 1.75, I2 = 31%, p = 0.23), or on r-MSSD (MD = − 0.14, 95% CI − 3.52 to 3.25, I2 = 46%, p = 0.94). Overall risk of bias was graded as low across the selected RCTs. Conclusion: SGLT-2 inhibitor treatment in patients with T2DM does not seem to provide any significant beneficial effect on CAN indices. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function is a major determinant of prognosis and adverse outcomes in patients with heart failure (HF). It is largely unknown if HF with mildly reduced ejection fraction (HFmrEF) patients have some special characteristics in RV function (RVF) that may distinguish them from HF with reduced or preserved ejection fraction (HFrEF or HFpEF) patients. Standard echocardiography was performed to estimate RVF [tricuspid annular systolic velocity (TDSV), plane systolic excursion (TAPSE), TAPSE to pulmonary artery systolic pressure (TAPSE/PASP) and RV myocardial performance index (MPI-TEI index)] in a cross-sectional study. In 306 participants, the RV systolic function evaluated with TAPSE and TDSV was impaired in 39.1 and 24.2%, respectively. TAPSE, TAPSE/PASP and TDSV were lower in HFmrEF compared with HFpEF and higher compared with HFrEF (p < 0.001 for among-groups comparison). RV diastolic dysfunction varied between 12.6 and 43.8% depending on the echocardiographic parameter. Diastolic RVF determined by tricuspid inflow E/A wave ratio (Et/At) was impaired in less patients with HFmrEF compared with those with HFpEF or HFrEF (25.9% vs 48.4% vs 56.3%; p = 0.030, respectively). RV diastolic dysfunction by et'/at' (tissue Doppler tricuspid valve annulus e' and a' waves) was impaired in less patients with HFmrEF compared with HFrEF (11.8% vs 33.3%; p = 0.019). A multivariate regression analysis revealed a significant association between RV and LV systolic dysfunction. The present study shows a high prevalence of RV dysfunction in HFmrEF patients. Study findings provides some new insights on RV and LV systolic dysfunction coupling whereas RV diastolic dysfunction was not dependent on LV systolic dysfunction. [ABSTRACT FROM AUTHOR]

Purpose of Review: In this narrative review, we aim to summarize the latest data on the association between primary aldosteronism and resistant hypertension, as well as to emphasize the necessity for screening for primary aldosteronism all patients with resistant hypertension. Recent Findings: Epidemiological data suggests that up to one out of five patients with resistant hypertension suffer from primary aldosteronism. Patients with primary aldosteronism have increased incidence of renal disease, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea, as well as they are characterized by an extended target organ damage and increased cardiovascular morbidity and mortality. Specific treatments for primary hyperaldosteronism (adrenalectomy and mineralocorticoid receptor antagonists) have significant impact on blood pressure, can reverse target organ damage, and mitigate cardiovascular risk. Summary: All patients with resistant hypertension should be evaluated for primary aldosteronism. Patients diagnosed with the disease may further undergo lateralization with adrenal vein sampling in order to receive the optimal therapeutic option which results in significant improvements in quality of life and cardiovascular profile. [ABSTRACT FROM AUTHOR]

Aims: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. Methods: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. Results: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0–9.7), 22.4 (16.0–29.1) and 77.0 (55.0–102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. Conclusions: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH. [ABSTRACT FROM AUTHOR]

Cardiovascular risk is increased in patients with autoimmune rheumatic diseases. Endothelial, erythrocyte and platelet microvesicles (MVs) are elevated in patients with cardiovascular diseases and represent novel markers of endothelial dysfunction and thromboinflammation. We tested whether their levels are increased in patients with autoimmune rheumatic diseases (ARDs) in the absence of disease flare and cardiovascular comorbidities. Well-controlled patients with rheumatoid arthritis or systemic lupus erythematosus were studied, provided they were free from cardiovascular comorbidities and established cardiovascular disease. We additionally studied (a) a control group consisting of healthy volunteers and (b) a reference group including patients with stable coronary artery disease (CAD). MVs were measured using a standardized flow cytometry protocol. In a population of 74 participants, patients with ARDs (n = 17) presented increased levels of both endothelial (283.3 ± 195.0/μL vs 168.5 ± 54.8/μL, p = 0.029) and platelet MVs (374.0 ± 275.3/μL vs 225.7 ± 101.1/μL, p = 0.046) compared to controls (n = 34), whereas erythrocyte MVs did not significantly differ. In addition, patients with ARDs showed similar levels of endothelial MVs compared to CAD patients (n = 23) (283.3 ± 195.0/μL vs 297.0 ± 211.8/μL, p = 0.846). Platelet MVs were significantly associated with disease duration, and erythrocyte MVs with patients' perceived disease activity. In conclusion, increased levels of endothelial and platelet MVs may be evident in patients with ARDs, even in the absence of disease flares and before the establishment of cardiovascular complications. Levels of endothelial MVs resemble those of patients with profound atherothrombotic profile. The prognostic potential of MVs in terms of cardiovascular disease prevention warrants further investigation in patients with ARDs. [ABSTRACT FROM AUTHOR]

Introduction: Microvascular dysfunction is the key element in the pathogenesis of systemic sclerosis (SSc), whereas the contribution of large and medium size vessel abnormalities is yet to be established. The aim of the present study is to assess the association between micro- and macrovascular function by utilizing a broad spectrum of assessments of vascular performance. Methods: We included consecutive, consenting SSc patients who underwent nailfold video capillaroscopy (NVC) for microcirculation evaluation. Peripheral and central systolic and diastolic blood pressure, carotid intima-media thickness (cIMT), aortic augmentation index (AIx) corrected for a heart rate of 75 beats per minute (AIx-75), and carotid-femoral pulse wave velocity (PWV) were also performed to assess macrovascular function. Cardiovascular risk disease (CVD) algorithms were also calculated and included in the analysis. Results: A total of 81 patients (6 males) were studied with mean age 55.44 ± 13.40 years. Reduced capillary density was inversely correlated with arterial stiffness (Alx-75) and augmentation pressure (r = − 0.262, p = 0.018, and r = − 0.249, p = 0.025 respectively). Alx was significantly lower in the early compared to late pattern (28.24 ± 11.75 vs 35.63 ± 10.47, p = 0.036). A significant trend was found among NVC patterns with Alx-75 values being higher with the progression of microangiopathy towards the "late" group (26.36 ± 10.90 vs 30.81 ± 11.59 vs 35.21 ± 7.90, p = 0.027 for trend). Similarly, Framingham risk score and Atherosclerotic Cardiovascular Disease score were progressively higher across the worsening NVC patterns (4.10 ± 4.13 vs 2.99 ± 2.72 vs 6.36 ± 5.65, p = 0.023, and 6.99 ± 7.18 vs 5.63 ± 4.41 vs 12.09 ± 9.90, p = 0.019, respectively, for trends). Finally, QRISK3 (10-year cardiovascular disease risk) and ASCVD (Atherosclerotic Cardiovascular Disease) scores were inversely correlated with the number of capillaries (r = − 0.231, p = 0.048, and r = − 0.260, p = 0.038 respectively). Conclusion: These data suggest that CVD risk scores and macrovascular parameters are strongly correlated with microvasculopathy in patients with SSc. Key Points • Microangiopathy is the hallmark of SSc, but the relationship between subclinical atherosclerosis and small vessel disease remains unknown. • Arterial stiffening and CVD risk scores are positively associated with the degree of progression of peripheral microvasculopathy assessed with NVC. • The results of the study suggest an association between NVC abnormalities and higher CVD risk in SSc patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) represents a global public health nightmare. The "cytokine storm," the most prominent underlying pathophysiologic mechanism of this disease, can theoretically be targeted at several stages. Janus kinase (JAK) inhibitors constitute a drug class that could ameliorate the inflammatory response and enhance antibody production. Herein, we aimed to evaluate the efficacy of JAK inhibitors in patients with COVID-19, performing the most updated relevant meta-analysis. We searched two major databases for randomized controlled trials (RCTs) enrolling adult patients with documented COVID-19 in the in-hospital setting, assigned either to JAK inhibitor treatment plus standard of care or standard of care alone. We set as primary efficacy outcome the endpoint of COVID-19 death on day 28 and as secondary efficacy composite outcome that of mechanical ventilation or initiation of extracorporeal membrane oxygenation (ECMO). We finally pooled data of interest from 4 RCTs in a total of 1338 subjects with documented COVID-19 infection, utilizing the following JAK inhibitors: baricitinib, ruxolitinib, tofacitinib, and nezulcitinib. Treatment with JAK inhibitor compared to control resulted in a significant reduction in the risk for COVID-19 death by 43%, while it also led to a significant decrease in the risk for mechanical ventilation or ECMO initiation by 36%. Herein, we demonstrate a clear benefit with JAK inhibitors added to standard of care in patients with COVID-19 in terms of risk reduction concerning major outcomes. Larger RCTs will elucidate their place in treatment armamentarium against COVID-19. [ABSTRACT FROM AUTHOR]

Keywords: SGLT-2 inhibitors; Mortality; Cardiovascular death; Diabetes mellitus EN SGLT-2 inhibitors Mortality Cardiovascular death Diabetes mellitus 1185 1187 3 06/07/22 20220601 NES 220601 Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s40200-021-00955-4. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are now considered as the optimal treatment option for patients with T2DM and concomitant cardiovascular or renal disease. [Extracted from the article]

A collector samples coupons with replacement from a pool containing g uniform groups of coupons, where "uniform group " means that all coupons in the group are equally likely to occur (while coupons of different groups have different probabilities to occur). For each j = 1,..., g, let Tj be the number of trials needed to detect Group j, namely to collect all Mj coupons belonging to it at least once. We first derive formulas for the probabilities P{T1 < ... < Tg} and . After that, without severe loss of generality, we restrict ourselves to the case g = 2 and compute the asymptotics of P{T1 < T2} as the number of coupons grows to infinity in a certain manner. Then, we focus on T:= T1 ∨ T2, i.e. the number of trials needed to collect all coupons of the pool (at least once), and determine the asymptotics of E[T]and V [T], as well as the limiting distribution of T (appropriately normalized) as the number of coupons becomes large. [ABSTRACT FROM AUTHOR]

Bullying is a significant problem in the USA, with 1 in 5 middle school students reporting being a target of bullying. Although prevalence rates of bullying are higher among students in low-income communities and among minority students in ethnically blended schools, the majority of research on bullying prevention has been conducted with primarily White samples. Further, many available anti-bullying programs require significant resources for implementation, leading to barriers for schools in low-income communities. The purpose of this study was to examine the effectiveness of a brief, bystander preventive intervention (STAC) adapted to be culturally appropriate for students in ethnically blended schools in low-income communities. The STAC acronym stands for the four strategies students are taught to use to intervene in bullying behavior: "stealing the show," "turning it over," "accompanying others," and "coaching compassion." Participants were sixth grade students (N = 147) at an ethnically blended school in a low-income community. The social validity of the program was assessed through measures of program acceptability, student learning, and use of intervention strategies in bullying situations. Program outcomes included bullying behavior, depressive symptoms, and social anxiety. Results indicated that students trained in the adapted STAC program found the program to be acceptable, reported a significant increase in knowledge and confidence, and reported using the program strategies post-training. Students also reported a significant decrease in bullying behavior, depressive symptoms, and social anxiety. Findings suggest that the adapted STAC program is a promising approach for bullying prevention for ethnically blended middle schools in low-income communities. [ABSTRACT FROM AUTHOR]

White lupin (Lupinus albus L.) is an annual crop cultivated for its protein-rich seeds. It is adapted to poor soils due to the production of cluster roots, which are made of dozens of determinate lateral roots that drastically improve soil exploration and nutrient acquisition (mostly phosphate). Using long-read sequencing technologies, we provide a high-quality genome sequence of a cultivated accession of white lupin (2n = 50, 451 Mb), as well as de novo assemblies of a landrace and a wild relative. We describe a modern accession displaying increased soil exploration capacity through early establishment of lateral and cluster roots. We also show how seed quality may have been impacted by domestication in term of protein profiles and alkaloid content. The availability of a high-quality genome assembly together with companion genomic and transcriptomic resources will enable the development of modern breeding strategies to increase and stabilize white lupin yield. White lupin is an annual crop cultivated for protein rich seeds and can produce cluster roots for efficient phosphate acquisition. Here, the authors generate high quality genome assemblies of a cultivated accession, a landrace, and a wild relative and provides insight into soil exploration and seed quality. [ABSTRACT FROM AUTHOR]

Antimony (Sb) is a toxic metalloid whose pollution has become a serious problem. However, studies on fungal endophytes resistant to antimony are virtually nonexistent. An endophytic fungal strain was isolated for the first time from the roots of Hedysarum pallidum Desf. which is a Sb accumulator Fabacea growing on mine cuttings. Experiments with high Sb increased concentrations (0, 5, 10, 20 and 30 mM Sb) were performed in order to assess the strain potential in contaminated environments bioremediation and to understand its Sb tolerance strategy. The isolated strain was identified as Aspergillus tubingensis MH189391 by morphological characteristics and phylogenetic analysis. It exhibited a minimum inhibitory concentration (MIC) of 500 mM Sb, i.e. 60,880 mg L−1, and maintained high amounts of biomass up to 30 mM Sb, i.e. 3652.8 mg L−1 of Sb. A stimulation of A. tubingensis growth and its antioxidant responses was observed at the level of 5 mM Sb, i.e. 609 mg L−1. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents increased significantly (p < 0.05) with Sb treatments. Oxidative stress induced significant increases (p < 0.05) in antioxidant biomarkers such as proline, catalase (CAT), and superoxide dismutase (SOD), but it resulted in a significant decrease of peroxidase (POD) and ascorbate peroxidase (APX) activities. Proline, CAT, SOD, H2O2 and MDA were significantly (p < 0.05) and positively correlated, which highlights their coactions in oxidative stress fighting. Results indicate that Aspergillus tubingensis has developed an important adaptation to excessive Sb concentrations and that it could be used in antimony-contaminated environments bioremediation. [ABSTRACT FROM AUTHOR]

It is well documented that bullying victimization and perpetration are associated with mental health problems, including anxiety and depressive symptoms. Although the majority of students report witnessing bullying as bystanders, very few studies have investigated whether negative consequences associated with bullying extend beyond targets and perpetrators to students who are bystanders. The present study examined the association between witnessing bullying and anxiety and depressive symptoms among middle school students. Middle school students (N = 130; grades 6th through 8th) completed questionnaires assessing experiences as a bystander, target, and perpetrator of bullying, as well as anxiety and depressive symptoms. Hierarchical regression analyses were conducted to determine whether bystander status was associated with anxiety and depressive symptoms over and above the effects of victimization and perpetration and to examine bullying victimization and perpetration as moderators of these relationships. Analyses indicated being a bystander was associated with higher levels of anxiety (β =.40, p <.001) and depressive symptoms (β =.37, p <.001) even after controlling for frequency of being a target or perpetrator of bullying. Bystanders who were also targets of bullying reported the highest level of depressive symptoms; however, being a target of bullying did not moderate the relationship between being a bystander and anxiety. Furthermore, bullying perpetration did not moderate the relationship between being a bystander and anxiety or depressive symptoms. Findings indicate witnessing bullying uniquely contributes to anxiety and depressive symptoms for middle school students. For student bystanders who are also targets of bullying, depressive symptoms may be particularly high due to co-victimization or re-victimization experienced when witnessing bullying. [ABSTRACT FROM AUTHOR]

Background: In addition to the normal process of ageing, frailty, defined as a geriatric syndrome, is becoming more prevalent. Around 10% of people over 65 years and 25-50% of those aged over 85 years are frail. Frail elderly are more vulnerable to external stressors and have an increased risk of adverse health outcomes. To tackle these challenges, European Union (EU) member states need to develop a health work force capable of the right skills mix. A goal-centred education and training of professionals is crucial for effective and efficient health care delivery for Europe’s greying population.Aims: The aim of this study was to systematically collect, review and critically appraise studies carried out to investigate the efficacy and effectiveness of comprehensive educational programmes for health professionals related to frailty prevention and/or frailty management.Methods: A systematic review was carried out searching the databases PubMed, CINAHL, Cochrane CENTRAL, Medline, Up to date and Embase. Additionally, a manual search of the reference lists and searches via Google Scholar and greylit.org was done.Results: No relevant publications addressing the evidence and sustainability of educational/training programmes for frailty prevention and/or frailty management were identified.Discussion: The result of an empty review is surprising because several educational programmes in different countries are currently run.Conclusions: A significant knowledge gap exists in the scientific literature regarding education and training of health care workers regarding prevention and management of frailty. Further research is needed to identify effective educational strategies for health professionals to prevent and manage frailty. [ABSTRACT FROM AUTHOR]

Abandoned mines are a recurrent problem for nearby communities in Mediterranean regions because mine tailings represent a major source of polymetallic contamination. Metal contaminants are emitted in mining areas and dispersed by wind and water erosion in the surroundings. The goal of this literature review was to identify the specific features of polymetallic contamination arising from abandoned mines in the Mediterranean regions. Mediterranean climate conditions and local geochemical context are the most important factors that control the metal-bearing particle dispersion toward the different compartments of ecosystems. Acid mine drainage, as an important source of damage to the environment, is limited to a certain extent by the predominance of carbonate rocks in the Mediterranean regions. In opposite, aeolian contamination is specific to the semiarid conditions of the Mediterranean climate. In this context, impacts on different compartments such as agricultural soils and edible plants or human populations were underlined. The analysis of environmental laws and regulations of North and South Mediterranean countries shows that one of the main differences is the lack of identification and definition of mining waste as a public concern in the latter countries. In order to limit the transfer of contaminants from mining waste to the different components of the environment, phytostabilization of mine tailings was considered as the more adapted green technology even in the Mediterranean region where water access is limited. Finally, this review of polymetallic pollution from abandoned mines in Mediterranean regions enabled to identify priority actions for future research. [ABSTRACT FROM AUTHOR]

Postural control is an adaptive process that can be affected by many aspects of human behavior, including emotional contexts. The main emotional contexts that affect postural control are postural threat and passive viewing of aversive or threatening images, both of which produce a reduction in postural sway. The aim of the present study was to assess whether similar stress-related changes in postural sway can be observed using stress induced by social evaluative threat (SET) while performing arithmetic tasks. Twelve young adults performed an arithmetic and a postural control task separately, concurrently, and concurrently with added time pressure in the arithmetic task. In the final condition, participants were given negative feedback about their performance in the arithmetic task and performed it again while being observed (SET condition). Results showed that stress increased linearly with task demand. Postural sway and reaction times were not affected by the first two conditions; however, when time pressure was introduced, reaction times became faster and sway amplitude increased. Finally, introduction of SET caused the predicted reduction in postural sway and an increase in reaction times relative to the time pressure condition. Our results suggest that stress induced using a combination of arithmetic tasks and social evaluative threat leads to systematic changes in postural control. The paradigm developed in the present study would be very useful in assessing interactions between cognition, stress, and postural control in the context of postural instability and falls in older adults. [ABSTRACT FROM AUTHOR]

Background/Introduction: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while 'real-world' data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. Methods: In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Results: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was −30/−12 and −29/−12 mmHg, while the reduction in 24-h ambulatory BP was −16/−9 and −15/−9 mmHg, respectively ( p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response ( p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. Conclusions: In our 'real-world' multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN. [ABSTRACT FROM AUTHOR]

Hypertension is a global public health problem affecting one-fourth of the world's population. A subset of these patients with resistant hypertension presents a particular management problem and suffers a marked increase in cardiovascular risk. Treatment options have been limited, but the past decade has witnessed the emergence of catheter-based renal denervation to interrupt the sympathetic nervous system, long considered to play an important role in the development and maintenance of hypertension. Phase 1 and 2 studies reported remarkable reductions in blood pressure and sparked an excessive exuberance that ground to a halt with negative results of the SYMPLICITY HTN-3 pivotal trial. The subsequent and sober reappraisal has shed light on potential failure modes. Armed with appropriately cautious optimism, the field has resumed its move forward to realize the potential for therapeutic application in hypertension and other conditions characterized by sympathetic overactivity. This article summarizes the rich experimental data, early surgical experience, and available clinical trial results for catheter platforms. It concludes with discussion of knowledge gaps, lessons learned, and future directions. [ABSTRACT FROM AUTHOR]

Heart failure is a life-limiting condition affecting over 40 million patients worldwide. Ischemic cardiomyopathy (ICM) is the most common cause. This study investigates in situ cardiac regeneration utilizing precision delivery of a novel mesenchymal precursor cell type (iMP) during coronary artery bypass surgery (CABG) in patients with ischemic cardiomyopathy (LVEF < 40 %). The phase IIa safety study was designed to enroll 11 patients. Preoperative scintigraphy imaging (SPECT) was used to identify hibernating myocardium not suitable for conventional myocardial revascularization for iMP implantation. iMP cells were implanted intramyocardially in predefined viable peri-infarct areas that showed poor perfusion, which could not be grafted due to poor target vessel quality. Postoperatively, SPECT was then used to identify changes in scar area. Intramyocardial implantation of iMP cells with CABG was safe with preliminary evidence of efficacy of improved myocardial contractility and perfusion of nonrevascularized territories resulting in a significant reduction in left ventricular scar area at 12 months after treatment. Clinical improvement was associated with a significant improvement in quality of life at 6 months posttreatment in all patients. The results suggest the potential for in situ myocardial regeneration in ischemic heart failure by delivery of iMP cells. [ABSTRACT FROM AUTHOR]

We investigated the nature of sensory integration deficits in postural control of young adults with ASD. Postural control was assessed in a fixed environment, and in three environments in which sensory information about body sway from visual, proprioceptive or both channels was inaccurate. Furthermore, two levels of inaccurate information were used within each channel (gain 1 and 1.6). ASD participants showed greater postural sway when information from both channels was inaccurate. In addition, control participants' ellipse area at gain 1.6 was identical to ASD participants' at gain 1, reflecting hyper-reactivity in ASD. Our results provide evidence for hyper-reactivity in posture-related sensory information, which reflects a general, rather than channel-specific sensory integration impairment in ASD. [ABSTRACT FROM AUTHOR]

Objectives: Prediabetes is recognized as a significant metabolic status, being a key factor in the occurrence of diabetes mellitus (DM). There is increasing evidence concerning microvascular complications in prediabetes most commonly in skin, kidneys and retina (1,2). Laser speckle contrast analysis (LASCA) is a non-invasive technique that can be used to evaluate skin microvascular function. Previous studies have shown skin microvascular dysfunction in patients with DM (3). However, to our knowledge, no previous study has evaluated skin microcirculation, using LASCA, in patients with prediabetes. Methods: In all subjects, forearm skin blood flow was recorded under standardized conditions using a laser speckle contrast imager (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyperemia (PORH) was assessed following a standardized protocol and data were analyzed with a signal processing software (PIMSoft, Perimed). The amplitude of PORH responses was expressed as a percentage increase between peak and baseline perfusion (%). Results: Twenty-nine individuals (14 patients with prediabetes and 15 controls) were studied. There wasn't any statistically significant difference regarding age, sex, body mass index and blood pressure levels between the two groups. At baseline, skin microvascular perfusion was significantly higher in patients with prediabetes compared to controls (50.9 ± 11.5 vs. 39.2 ± 8.7, p = 0.006) while during occlusion, perfusion was similarly reduced in both groups. Post occlusion reperfusion was significantly lower in the prediabetes group as compared to the controls (145.0 ± 42.8 vs. 195.2 ± 47.3% respectively, p = 0.007). Conclusions: We showed, for the first time, that individuals with prediabetes demonstrated skin microvascular dysfunction, that may reflect a more generalized microvascular damage. [ABSTRACT FROM AUTHOR]

Purpose: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC. Methods: Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent. Results: Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI ( p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle. Conclusions: Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC. [ABSTRACT FROM AUTHOR]

The Editor-in-Chief of the Journal of Cardiovascular Translational Research is issuing an Editorial Expression of Concern on this article [1]. [ABSTRACT FROM AUTHOR]