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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Wellcome Trust and British Heart Foundation. Background In-silico pacing mapping is a technique which involves using an anatomically-personalised image-based computational model to generate a ‘virtual’ clinical pace map for enhanced pre-procedural ablation planning of post-infarction ventricular tachycardia (VT). Utilising, as it does, a direct clinical ECG (or implanted device) recording of the clinical VT in order to construct the map, it has a number of advantages over other computational methods which attempt to simulate patient-specific VTs to identify ablation targets. However, accurate model construction relies on adequate scar imaging data, which may not be available with current clinical cardiac MR (CMR) sequences. Purpose To investigate the impact of scar imaging quality on the ability of in-silico pace-mapping to determine the VT origin. Methods VTs were simulated in three post-infarction porcine heart models reconstructed from high resolution (1mm isotropic) contrast-enhanced CMR data. Visual analysis of the VT circuits was performed to identify the VT site of origin (exit site) in each case (as the gold standard). The ECG of each simulated VT was computed and used as input for the construction of the in-silico virtual pace-mapping approach. Prior to pace map construction, the scar anatomy was modified to represent three different levels of imaging resolution: high resolution scar mapping (default); low resolution scar (representing standing clinical CMR sequences), obtained by performing dilation and erosion in the scar to close all inner pathways; and, finally, no scar (cardiac anatomy only, representing CT-based reconstructions). In-silico pace-mapping was performed by pacing the heart in N = 1000 sites from randomly chosen locations, on both surfaces and intramurally, within close proximity ( Results As can be seen in Figure 1, correlation between VT and paced ECGs was found to be strongest at pacing locations near the VT exit site in all models. Correlation coefficients were similar in value and distribution in models with high- (min: -0.49±0.27 and max: 0.92±0.05) and low-resolution scars (min: -0.46±0.29 and max: 0.93±0.05). While the correlation map in the absence of scar had smaller values when compared to the other two models (min: -0.50±0.24 and max: 0.71±0.09), the VT exit was still located near the pacing location with the strongest correlation: d = 9.47±2.83 (high-res), d = 6.63±6.35mm (low-res) and d = 18.60±7.10mm (no scar). Conclusion In-silico pace-mapping successfully detected the VT exit sites regardless the resolution of the scar. This finding suggest that the level of infarct anatomical detail has a minor effect on simulated paced activation to localize VT ablation.

Supplementary Figure 4 from Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis

Supplementary Figure 5 from Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis

Supplementary Figure 2 from Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis

Supplementary Figure 3 from Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis

Supplementary Figure 1 from Repression of RUNX1 Activity by EVI1: A New Role of EVI1 in Leukemogenesis

Recurring chromosomal translocations observed in human leukemia often result in the expression of fusion proteins that are DNA-binding transcription factors. These altered proteins acquire new dimerization properties that result in the assembly of inappropriate multimeric transcription complexes that deregulate hematopoietic programs and induce leukemogenesis. Recently, we reported that the fusion protein AML1/MDS1/EVI1 (AME), a product of a t(3;21)(q26;q22) associated with chronic myelogenous leukemia and acute myelogenous leukemia, displays a complex pattern of self-interaction. Here, we show that the 8th zinc finger motif of MDS1/EVI1 is an oligomerization domain involved not only in interaction of AME with itself but also in interactions with the parental proteins, RUNX1 and MDS1/EVI1, from which AME is generated. Because the 8th zinc finger motif is also present in the oncoprotein EVI1, we have evaluated the effects of the interaction between RUNX1 and EVI1 in vitro and in vivo. We found that in vitro, this interaction alters the ability of RUNX1 to bind to DNA and to regulate a reporter gene, whereas in vivo, the expression of the isolated 8th zinc finger motif of EVI1 is sufficient to block the granulocyte colony-stimulating factor–induced differentiation of 32Dcl3 cells, leading to cell death. As EVI1 is not detected in normal bone marrow cells, these data suggest that its inappropriate expression could contribute to hematopoietic transformation in part by a new mechanism that involves EVI1 association with key hematopoietic regulators, leading to their functional impairment. [Cancer Res 2007;67(12):5658–66]

Myelofibrosis (MF) is a disease associated with high unmet medical needs because allogeneic stem cell transplantation is not an option for most patients, and JAK inhibitors are generally effective for only 2 to 3 years and do not delay disease progression. MF is characterized by dysplastic megakaryocytic hyperplasia and progression to fulminant disease, which is associated with progressively increasing marrow fibrosis. Despite evidence that the inflammatory milieu in MF contributes to disease progression, the specific factors that promote megakaryocyte growth are poorly understood. Here, we analyzed changes in the cytokine profiles of MF mouse models before and after the development of fibrosis, coupled with the analysis of bone marrow populations using single-cell RNA sequencing. We found high interleukin 13 (IL-13) levels in the bone marrow of MF mice. IL-13 promoted the growth of mutant megakaryocytes and induced surface expression of transforming growth factor β and collagen biosynthesis. Similarly, analysis of samples from patients with MF revealed elevated levels of IL-13 in the plasma and increased IL-13 receptor expression in marrow megakaryocytes. In vivo, IL-13 overexpression promoted disease progression, whereas reducing IL-13/IL-4 signaling reduced several features of the disease, including fibrosis. Finally, we observed an increase in the number of marrow T cells and mast cells, which are known sources of IL-13. Together, our data demonstrate that IL-13 is involved in disease progression in MF and that inhibition of the IL-13/IL-4 signaling pathway might serve as a novel therapeutic target to treat MF.

Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder characterized by airflow limitation, persistent respiratory symptoms and chronic lung inflammation. Previous studies reported a robust relationship between COPD and coronary artery disease (CAD). Local and systemic inflammation, known to play a role in atherosclerosis development, has been reported in patients with COPD, and has been proposed as one of the possible pathogenetic factors linking COPD and CAD. However, data on atherosclerotic coronary pattern and coronary inflammation in COPD patients are lacking. Purpose To study the characteristics of atherosclerotic coronary plaques and local inflammation by using optical coherence tomography (OCT) in COPD patients presenting with acute coronary syndromes (ACS). Methods ACS patients undergoing intracoronary OCT imaging of the culprit vessel were retrospectively identified. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into 2 groups according to the presence or the absence of an established diagnosis of COPD, and coronary plaque features and MØI both at the culprit plaque site and along the culprit vessel were compared between the two groups. Results Among 146 ACS patients (mean age, 66,1±12,7 years, 109 males), 47 (32,2%) had COPD. Patients with COPD were older, were more frequently on therapy with an angiotensin receptor blocker, had lower hemoglobin, total cholesterol and triglycerides levels, and had higher serum creatinine levels. The prevalence of different mechanisms of ACS were similar between COPD and noCOPD patients (plaque rupture: 57,4% vs. 45,4%, plaque erosion: 23,4% vs. 32,3%, calcified plaque: 19,1% vs. 22,2%, respectively, overall p=0,381). OCT analysis of plaque microstructures showed that COPD patients had significantly higher prevalence of MØI (78,7% vs. 54,4%, p=0,005), thin cap fibroatheroma (TCFA) (48,9% vs. 22,2%, p=0,001), spotty calcium (68,1% vs. 26,3%, p Conclusions In ACS patients undergoing OCT imaging of the culprit vessel, COPD was an independent predictor of local plaque inflammation and plaque vulnerability both at the culprit site and along the culprit vessel. Our results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability. Funding Acknowledgement Type of funding sources: None.

Background Takotsubo syndrome (TTS) is associated with a non-negligible risk of in-hospital (IH) complications. Elevated left ventricular filling pressures (LVFP), measured invasively as LV end-diastolic pressure (LVEDP), showed to predict adverse IH outcomes in this population. Recently, novel indexes of left atrial (LA) function, including LA reservoir and LA pump strain, demonstrated a close correlation with increased LVFP in unselected patients. Purpose To assess the ability of LA reservoir and LA pump strain to improve non-invasive estimation of LVFP and to predict IH complications in TTS patients. Methods We retrospectively enrolled patients with confirmed TTS diagnosis at invasive left heart catheterization and coronary angiography. LVEDP was assessed invasively at the time of catheterization. Transthoracic echocardiography was performed with 48 hours from hospital admission. IH complications were collected, including occurrence of acute heart failure (pulmonary oedema/cardiogenic shock; Killip class III/IV), death from any cause and life-threatening arrhythmias. Results A total of 62 patients were analysed (72.2±10.1 years, female 80%). IH complications occurred in 25 (40.3%). Patients who experienced IH complications had higher LVEDP and lower LVEF, LA reservoir strain and LA pump strain values compared to patients without IH complications (all P≤0.001). At multivariate analysis, EF and LVEDP were independent predictors of worse IH outcomes (P≤0.001 and P=0.004 respectively). Correlation analysis proved that lower values of both LA reservoir and pump strain were associated with increasingly higher LVEDP (r −0.859, P≤0.001 and r −0.848, P≤0.001 respectively). Receiving operating characteristic (ROC) curve analysis showed that the AUC for LVEDP to predict IH complications was 0.814 (95% CI 0.679–0.949, P≤0.001) with an optimal cut-off value of 24.5 mmHg (sensitivity 77%, specificity 53%). Therefore, we performed ROC curve analysis to compare the ability of LA strain values and standard echocardiographic parameters currently used for non-invasive LVFP assessment to predict LVEDP ≥24.5 mmHg. As a result, we obtained higher AUC for LA reservoir and pump strain [0.909 (95% CI 0.818–0.999, P≤0.001) and 0.889 (95% CI 0.789–0.988, P≤0.001), respectively] vs E/e' 0.800 (95% CI 0.663–0.937, P≤0.001), LAVi 0.666 (P=0.092) and tricuspid regurgitation (TR) peak velocity 0.582 (P=0.596). The incorporation of LA strain values in a multivariable model including E/e' ratio, LAVi and TR peak velocity to predict a LVEDP ≥24.5 mmHg led to a significant incremental predictive value (changes in χ2=11.99; P=0.002). Conclusion In patients with TTS, lower LA reservoir and pump strain values correlate with increased LVEDP and improve non-invasive estimation of LVFP. LA strain analysis may be an easy tool to individuate subjects at higher risk of IH complications. Funding Acknowledgement Type of funding sources: None.

Background Coronary vasomotor abnormalities are an important cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). However, the role of air pollution in determining vasomotor disorders has never been investigated. Purpose In this study, we evaluated the association between long-term exposure to particulate matter (PM) PM2.5 and PM10 and coronary vasomotor disorders in NOCAD patients. Methods Patients with myocardial ischemia and NOCAD undergoing intracoronary provocative test with acetylcholine (ACh) were prospectively enrolled. The test was considered positive for epicardial coronary spasm in the presence of focal or diffuse epicardial coronary diameter reduction ≥90% in comparison with the relaxed state following intracoronary nitroglycerin administration given to relieve the spasm, associated with the reproduction of the patient's symptoms and ischaemic ECG shifts. Both patients with chronic myocardial ischemia (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA) were enrolled. Based on each case's home address, exposure to PM2.5 and PM10 was assessed. Only patients with >2 years of available data on air pollution exposure prior to coronary angiography were included. Results We enrolled 287 patients (median age 62.0 years [52.0–70.0], 149 [51.9%] males): 161 (56.1%) INOCA and 126 (43.9%) MINOCA. One hundred seventy-six patients (61.3%) had positive provocative test. Exposure to PM2.5 (Figure 1) and PM10 was higher in patients with a positive provocative test (p Conclusions We provide novel insights into the missing link between air pollution and ischemic heart disease. In particular, higher exposure to air pollution in patients with myocardial ischemia and NOCAD is associated with coronary vasomotor abnormalities, and PM2.5 is an independent risk factor for the occurrence of epicardial spasm and for MINOCA as clinical presentation. Funding Acknowledgement Type of funding sources: None.

Mini-Mental State Examination (MMSE) lacks of sensitivity in detecting cognitive deficits associated with subcortical damage. The HIV-Dementia Scale (HDS), a screening tool originally created for detecting cognitive impairment due to subcortical damage in HIV + patients, has proved to be useful in other neurological diseases. Until now, an Italian version of the HDS is not available. We aimed at: (1) validating the HDS Italian version (HDS-IT) in a cohort of cognitively healthy subjects (CN); (2) exploring the suitability of HDS-IT in detecting cognitive impairment due to subcortical damage (scCI). The psychometric properties of the HDS-IT were assessed in 180 CN (mean age 67.6 ± 8.3, range 41–84) with regard to item-total correlation, test–retest reliability and convergent validity with MMSE. Item-total correlations ranged 0.44–0.72. Test–retest reliability was 0.70 (p p scCI subjects (mean age 64.9 ± 10.6, range 41–84). Mean HDS-IT total score was close to the original version and significantly lower in the scCI group compared to CN (8.6 ± 3.6 vs. 12.6 ± 2.5, p p

For the first time in the literature, a case of Sars-Cov-2 infection after lung Transplantation has been described. This case, particularly rare, brought attention on the in-depth screening for Sars-CoV-2 on lung donor. In addition to infectious problems, it is important to focus attention on medico-legal issues related to this case. In fact, from the point of view of professional responsibility, in theory, there could be criteria for identifying professional responsibility. The author analyzes the possible presence of medical liability in this specific case.

Background Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Purpose We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case's home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. Results We included 136 patients [median age 67.0 years (56.2–76.0), 104 (76.5%) male]. Sixty-six patients (48.5%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was an independent predictor for PR (OR=1.133, 95% CI [1.020–1.258], p=0.019). Moreover, exposure to higher levels of PM2.5, PM10 and CO was an independent predictor for the presence of TCFA, while PM2.5 and CO levels predicted the presence of MØI. Interestingly, PM2.5, PM10 and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, p=0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, p Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system. Funding Acknowledgement Type of funding sources: None. Air pollutants exposure and OCT featuresROC curve analysis

Foetal spleen is described as a transient focus of haematopoiesis between the 3(rd) and 5(th) month of gestation: this function is however entirely replaced by the bone marrow before the end of pregnancy. This study identifies haematopoiesis in foetal spleen by exploring changes of echogenicity during its development throughout gestation. Two intervals of pregnancy were studied: Mid-Pregnancy (Mid-P, 19-23 weeks) and End-Pregnancy (End-P, 37-41 weeks). The foetal spleen was investigated in 80 pregnant women (41 vs 39). Due to quality criteria the comparison was made between 60 images (30 Mid-P vs 30 End-P). The acquisition of splenic parenchyma was followed by clustering segmentation. We identified two new parameters resulted from the clustering segmentation: Dark Ratio (DR) and Light Ratio (LR). These are related to splenic echogenicity expressing the percentage of dark and light signal in the clustered image, influenced by blood cellularity. The mean of DR value was different among the 2 groups (0.0631 vs 0.0483, P = 0.014), while LR did not show any significant differences. We conclude that DR may represent a reliable radiomic parameter in the determination of extramedullary haematopoiesis in the spleen.

Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

The article's author has sought to summarize the regulatory and legal evolution of accidental criminal liability of doctors starting from earliest positions up until the enactment of the Gelli-Bianco law. An in-depth analysis is laid out based on the Italian Supreme Court Joint Sections ruling n. 8770/2018 (so-called Mariotti decision). The author has also elaborated upon the notion of varying degrees of guilt, which was taken out of the law's wording, to be later reintroduced as a concept by judicial interpretation. It is worth noting that Article 3 of the Balduzzi decree, article 590 sexies of the Italian Criminal Code and the reference to article 2236 of the Civil Code reflect an awareness on the part of legislators that medical liability needs to be limited. Clearly, the approach based on lawfulness alone, which protects from liability physicians that have adhered to guidelines, has been dismissed, superseded by the notion of minor fault. Nonetheless, the new legislation, in the author's estimation, constitutes a standard particularly ill-suited to modern medical practice, which has a high degree of complexity. The author concludes that it might be worth considering a more balanced alternative: getting back to the notion of fault, considering minor fault relevant, rather than major fault.

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies. © The Authors 2019.

The authors have sought to expound upon and shed a light on the rise of nootropics, which have gradually taken on a more and more relevant role in workplaces and academic settings.Multidisciplinary databases have been delved into by entering the following keys: "nootropics", "cognitive enhancement", "workplace", "productivity", "ethics", "bioengineering". In addition, a broad-ranging search has been undertaken on institutional websites in order to identify relevant analysis and recommendations issued by international institutions and agencies. Papers and reports have been independently pored over by each author. This search strategy has led to the identification of 988 sources but only 64 were considered appropriate for the purposes of the paper after being selected by at least 3 of the authors, independently.The notion of an artificially enhanced work performance - carried out by the 'superworker' - is particularly noteworthy and resonates with the conception of contemporary work on so many different levels: the rising need and demands for higher degrees of flexibility and productivity on the job, the implications of a '24/7' society, where more and more services are available at any time, the ever greater emphasis on entrepreneurial spirit, individual self-reliance and self-improvement, and last but not least, the impact of an ageing society on economic standards and performance.Moreover, it is worth mentioning that human enhancement technologies will predictably and increasingly go hand in hand with gene editing, bioengineering, cybernetics and nanotechnology. Applications are virtually boundless, and may ultimately affect all human traits (physical strength, endurance, vision, intelligence and even personality and mood).

Extensive scientific evidence shows that there is a broad spectrum of substances used as adulterants, whose effects on the user's health may be extremely harmful. The degree of purity of the drugs most commonly abused is highly variable depending on the region or epidemiological context. Practices of drug adulteration have been substantially evolving over the years: a significant trend has been observed in the last decade indicating a decline in the average purity of most drugs. Although the most frequent adulterants of common street drugs have long been well known, the rise of synthetic opioids has inevitably entailed gaps in knowledge in terms of the substances being used and their composition, which constitutes an even greater threat to public health.

The present letter is meant as a response to the commentary titled "Medically-assisted procreation and the rise of off-center, new types of "parenthood": it is incumbent upon lawmakers to intervene", which was published in issue 4, 2019, of the La Clinica Terapeutica journal. Newly available reproductive techniques have given rise to new opportunities to fulfill one's wishes for parenthood. Such developments have caused procreation to be perceived as a right, intended as the right to «artificial» procreation. Not only do such trends impact those couples who travel abroad in order to have children through heterologous fertilization and surrogacy: singles and same-sex couples pursue those avenues as well in order to become parents. In the article which we are commenting upon, the author has perused the evolving jurisprudence on that subject, pointing out how necessary it is for lawmakers to step in and clearly define the rights of all parties involved, minors in particular.

Cultivation of tiger grouper (Epinephelus fuscoguttatus) in Floating Net Cages in several locations in Bireuen Regency has developed. The potential disease issue can be caused by bacteria, viruses, fungi, or parasites. The purpose of this study was to determine the effectiveness of mangosteen peel extract capsules (Garcinia mangostana L) against bacterial disease in tiger grouper. This research was carried out in April 2019 at the MIPA Laboratory of Al Muslim University and the laboratory of PT. Centra Proteina Prima, Bireuen Regency. The design used was a completely randomized design with four treatments (0%, 10%, 20%, and 30% mangosteen peel extract capsules) with three replications. The parameters studied in this study including the diameter of the inhibition and the observation of MBC (Minimum Bacterial Concentration). The result showed that the administration of mangosteen peel extract capsules with doses of 10%, 20%, and 30% has no significant effect on reducing disease-causing bacteria in grouper grown on TSA media. Positive results were obtained on positive (+) MBC observations, presumably due to the small dose of mangosteen peel extract capsules given so that it could not kill bacteria grown in dishes with an inhibition range of 0 mm.Introduction

We present a 47-year-old, South-African origin, woman with a background of stable monoclonal gammopathy of unknown significance (MGUS) who attended A&E with a history of coryzal symptoms associated with persistent fever, lymphadenopathy and a new onset of rash, not responding to antibiotics and paracetamol. A trial of high-dose steroids resolved symptoms. Bone marrow biopsy confirmed a progression of MGUS into multiple myeloma and her axillary lymph node biopsy analysis supported a diagnosis of Kikuchi-Fujimoto disease (KFD). This is an unusual presentation where KFD has been noted alongside MGUS progression to multiple myeloma. Haematology follow-up is underway.

Background The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. Methods Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/− methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. Results HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. Conclusion This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.

The purpose of this paper is to understand organizational communication and work stress on employee performance. The method used is an explanatory survey, and a population of 32 respondents. The analysis technique used is multiple linear regression processed using SPSS 16.0, the questionnaire is used as a research instrument to collect data from respondents. Important employee performance by organizational communication but not significant and employee performance interests by positive and significant. Organizational communication and work stress are used to improve employee performance. This study was used to describe the influence of organizational communication, work stress on the performance of employees in production employees of PT. Indolakto. The object that becomes the unit of analysis in this study is employees of PT. Indolakto Jakarta. The independent variables in this study are organizational communication and work stress, and the dependent variable is employee performance

Myelodysplastic syndrome and myeloproliferative neoplasms are clonal myeloid disorders arising from haematopoietic stem cells that have the tendency to progress into acute myeloid leukaemia. Multiple prognostic scoring systems have been proposed and utilised in clinical practice to predict disease evolution, however none of them can predict treatment response. In solid tumours, the relationship between the pro-phagocytic calreticulin and the anti-phagocytic CD47 is repeatedly investigated. Overexpression of calreticulin has been documented to produce a pro-phagocytic signal in solid tumour and it is often counteracted by a concomitant expression of the anti-phagocytic CD47 as they act in response to one another, reflecting an apoptosis vs survival mechanism in response to chemotherapy. The role of both calreticulin and CD47 are currently poorly understood in myeloid malignancies including myelodysplastic syndrome and myeloproliferative neoplasms. The aim of this review is to elaborate on the current understanding round the roles and implications of calreticulin and CD47 signalling with in solid and haematological cancers, discuss potential roles for calreticulin and CD47 expression in transformation of myeloid cells in patients with MDS or MPN into AML and how these advances are starting to be used to design new therapeutic strategies to determine disease progression and treatment response in both solid cancer and myeloid malignancies.

The demand for agricultural commodities increases from year to year, so farmers also have to increase the production of agricultural products. Farmers can increase agricultural yields through the excessive use of inorganic fertilizers. This causes many problems for the environment, so it is required to reduce the use of inorganic fertilizers in agricultural land. This study aimed to determine the effect of a combination of organic and inorganic fertilizers on the growth and yield of rice. This research was carried out in a screen house in Jatisela, Gunung Sari Subdistrict, Lombok from June to October 2020. The three treatments used in this study were P0 N0 with no organic and inorganic fertilizers; P0 N100 with a dose of 100% inorganic fertilizer and P50 N50 with a dose of 50% organic fertilizer and 50% inorganic fertilizer. The results showed that the combination of organic fertilizers (50%) and inorganic fertilizers (50%) can increase the growth and yield of rice in the screen house compared to control plants and plants which given only 100% inorganic fertilizers. In summary, the combination of organic and inorganic fertilizers can reduce the use of inorganic fertilizers.

Exessive use of inorganic fertilizers in rice production systems, causes various negative effects in the environemnt, such as reducing soil fertility and increases pollution, which disturbs agricultural sustainability. Understanding raw materials for developing organic fertilizers which are cheap and adaptive to our environment, is an important study recently. Many researchers reported that brown algae could increase growth and yield of several species of plants. This due to brown algae extract contain plant growth hormone and essential elements to stimulate growth and production of plants. This article report growth and yield of rice plants suplied with mixtured extract of brown algae. Several species of brown algae were collected in coastal beach of Lombok. The seaweeds were cutted into small peaces, extracted with boiled water for 30 minute and filtered using filter whatman no.1 to get solid and liquid extract. Mixtured solid extracts were added in soil media. On the other hand, the mixtured liquid extracts were sprayed to rice plants during vegetative growth. The results shown that mixtured solid extracts increased growth and yield of rice plants. However, mixtured liquid extract did not stimulate growth and yield of rice plants. This suggests that brown algae is a potential raw material for development of organic fertilizers, which are adaptive to environment to support sustainable agriculture.

The size distribution, length-weight relationship and factor condition of three species male fiddler crab (Tubuca dussumieri, Gelasimus vocans and Austruca perplexa) from jaboy mangrove wetland, Sabang, Indonesia were examined. 50 samples from each species was collected from three station using digging method and cast net. Samplings were carried out during May 2019. The carapace length (CL) and total weight (TW) was measured using a digital caliper (standard error: 0.01 mm) and digital scale (standard error: 0.01 g). Result showed that Tubuca dussumieri, Gelasimus vocans and Austruca perplexa were found in the size range of 12.37-17.19 mm, 12.03-16.46 mm, 7.79-10.39 and mm carapace length, respectively. Besides, the total weight varied from 2.09-8.20 g, 2.85-5.07 g and 1.15-2.26 g, respectively. All species of male fiddler crab showed negative allometric growth (b < 3). The highest value of b was founded in Tubuca dussumieri, while the lowest was founded in Gelasimus vocans were 2.659 and 1.299, respectively. Nevertheless, Austruca perplexa has a higher value of factor condition than Tubuca dussumieri and Gelasimus vocans.

Our objective was to describe incidence and clinical features of ALS from a prospective population-based study in Emilia Romagna Region (ERR). From 2009 onwards, a prospective registry recorded all incident cases of ALS among residents in the ERR (population, 4.4 million inhabitants), involving 17 neurological departments. For each patient, detailed demographic and clinical information was collected by caring physicians. Results showed that from 1 January 2009 to 31 December 2011, 347 patients received a new diagnosis of ALS with a crude incidence rate of 2.63/100,000/year. There was micro-geographic heterogeneity throughout ERR, with higher incidence rates in the low density population (3.27/100,000) (p < 0.01). ALS patients have been more frequently employed in agriculture than the general ERR population (8.64\% vs. 4.6\%, p < 0.01). Clinical features were similar to those described in previous population based studies. In conclusion, we report incidence rates similar to those reported by European registries, reflecting good accuracy of our prospective study. We confirmed previous studies reporting higher incidence rates in rural areas and among agricultural workers. Although genetics has been gaining increasing importance in ALS aetiology, some epidemiological data are still unexplained. Identifying geographical areas or populations with high incidence rates can be a starting point for identifying environmental risk factors. Further studies having this specific aim can shed light on these topics.