Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up

BACKGROUND: Intima-media thickness (IMT) is a validated marker of preclinical atherosclerosis and a predictor of cardiovascular events. PATIENTS: We studied a population of 529 asymptomatic patients (age 62\u2009\ub1\u200912.8 years), divided into two groups of subjects with and without Metabolic Syndrome (MetS). METHODS: All patients, at baseline, have had a carotid ultrasound evaluation and classified in two subgroups: the first one without atherosclerotic lesions and the second one with preclinical atherosclerosis (increased IMT or asymptomatic carotid plaque). Cardiovascular endpoints were investigated in a 20-years follow-up. RESULTS: There were 242 cardiovascular events: 144 among patients with MetS and 98 among in healthy controls (57.4% vs. 35.2%; P\u2009<\u20090.0001). 63 events occurred in patients with normal carotid arteries, while 179 events occurred in patients with preclinical atherosclerosis (31.8% vs. 54.1%; P\u2009<\u20090.0001). Of the 144 total events occurred in patients with MetS, 36 happened in the subgroup with normal carotid arteries and 108 in the subgroup with preclinical atherosclerosis (45% vs. 63.15%; P\u2009=\u20090.009). 98 events occurred in patients without MetS, of which 27 in the subgroup with normal carotid arteries and 71 in the subgroup with preclinical atherosclerosis (22.88% vs. 44.37%; P\u2009=\u20090.0003). In addition, considering the 63 total events occurred in patients without atherosclerotic lesions, 36 events were recorded in the subgroup with MetS and 27 events in the subgroup without MetS (45% vs. 22.88%; P\u2009=\u20090.0019). Finally, in 179 total events recorded in patients with preclinical carotid atherosclerosis, 108 happened in the subgroup with MetS and 71 happened in the subgroup without MetS (63.15% vs. 44.37%; P\u2009=\u20090.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P\u2009=\u20090.01, HR: 0.7366, CI: 0.5479 to 0.9904). CONCLUSIONS: Preclinical atherosclerosis leads to an increased risk of cardiovascular events, especially if it is associated with MetS

Early induction of bedside pneumoperitoneum in the management of residual pleural space and air leaks after pulmonary resection

Background: The pneumoperitoneum to treat prolonged air leaks or pleural space problems after pulmonary resection has been successfully used for decades. The aim of the study is to describe our experience with the early induction of therapeutic pneumoperitoneum (TP). Methods: We reviewed the data of 103 consecutive patients undergoing TP between September 2011 and September 2019. Patients were divided into two groups according to the time of the induction of TP: early application (≥72&nbsp;h) and standard application (&gt;72&nbsp;h). Results: In total, 52 early TP and 51 standard TP were analyzed. The median time of TP induction was 2 (1–3) versus 8 (5–11) postoperative days (POD) (p &lt; 0.001). The time for obliteration of the residual pleural space (7 vs.9&nbsp;days, p = 0.805) and the time of resolution of the air leaks (14 vs. 16&nbsp;days, p = 0.663) didn’t differ between the two groups, but a favorable trend was observed in the early group. The hospital stay was lower for patients undergoing early pneumoperitoneum: 9 versus 18&nbsp;days (p &lt; 0.001). The multivariate analysis showed that POD of induction of TP (p &lt; 0.001), time of resolution of the air leak (p &lt; 0.001) and Heimlich valve (p = 0.002) were independent variables associated with the hospital stay. Conclusions: The use of TP whenever a space problem or air leaks occur after pulmonary resections is safe and effective. Its early use (≤72&nbsp;h) accelerates the hospital stay, eventually reducing the time of resolution of the air leak and residual pleural space

Multiparametric cardiac magnetic resonance assessmenti in sickle-beta-thalassemia

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project receives "no-profit support" from industrial sponsorships (Chiesi Farmaceutici S.p.A., ApoPharma Inc.). Background. Sickle β-thalassemia (Sβ-thal) is a hereditary hemoglobinopathy resulting from the combined heterozygosity for sickle cell and β-thalassemia genes. Cardiac involvement in Sβ-thal patients has been poorly investigated. Aim. We aimed to evaluate myocardial iron overload and cardiac function by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. Methods. One hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell disease (SCD) patients. Biatrial and biventricular function CMR parameters of Sβ-thal patients were compared with those of 111 healthy volunteers, matched by gender and age. Myocardial iron overload (MIO) was assessed by T2* technique. Cine images were acquired to quantify biventricular function. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Results. In Sβ-thal and SCD patients morphological and functional MR parameters were not significantly different, except for left atrial area and SVI (p = 0.023 and p = 0.048, respectively) that were significantly higher in SCD patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters except for LVEF that was significantly lower (Fig.1). Conclusions. The CMR analysis confirmed that Sβ-thal and SCD patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCD-specific bi-atrial and biventricular reference values

A Community-Based Marketing Campaign at Farmers Markets to Encourage Fruit and Vegetable Purchases in Rural Counties with High Rates of Obesity, Kentucky, 2015-2016

Availability of farmers markets may increase fruit and vegetable consumption among rural residents of the United States. We conducted a community-based marketing campaign, Plate it Up Kentucky Proud (PIUKP), in 6 rural communities over 2 years to determine the association between exposure to the campaign and fruit and vegetable purchases, adjusted for Supplemental Nutrition Assistance Program recipient status. Logistic regression was used to examine the odds of the PIUKP campaign influencing purchases. Awareness of the PIUKP marketing campaign was significantly associated with a willingness to prepare fruits and vegetables at home. Using marketing strategies at farmers markets may be an effective way to improve fruit and vegetable purchases in rural communities

JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions

Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis

Preclinical atherosclerosis, metabolic syndrome and risk of cardiovascular events

Atherosclerotic disease is a chronic disorder developing insidiously throughout the life and usually progressing to an advanced stage by the time symptoms occur. In order to realize cardiovascular (CV) prevention, the detection of asymptomatic but diseased patients is crucial for an early intervention, since in these subjects there are opportunities to alter the progression of disease and the outcome (1). However, the simply analysis of risk factors don’t permits to identify always these subjects since it doesn’t informs about the effect that risk factors (RF) had already provoked and may more provoke on the individual vasculature. Besides, the risk factors known predict can explain only the 90 percent of cardiovascular disease (CVD) and traditional algorithms for prediction of CV risk failed to predict a proportion of cardiovascular events (CVE), realizing a “risk factors prediction gap” (2). It may be explained by several reasons: the epidemiology-derived models, based on the prediction of long-term risk, may not accurately predict short-term events, they don’t take into consideration emerging and novel risk factors; risk algorithms don’t identify, among patients with neither a previous history of CVD nor an high risk for atherosclerotic disease, those who will develop acute myocardial infarction and/or sudden coronary death as first CVD manifestation, and this may be due to the fact that the factors responsible of plaque formation and growth are not necessarily the same responsible of its instability and rupture, being the latter related to inflammation, thrombosis and plaque morphology (3).So, a possible approach to evaluate the individual global cardiovascular risk with more accurateness is to identify risk factors combination that more easily produces vascular damage, or alternatively, to evaluate directly the arterial wall and its damage degree. The former approach is performed by the evaluation of metabolic syndrome, the latter by the non-invasive study of pre-ATS markers

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345

Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI

Removing Systemic Barriers to Equity, Diversity, and Inclusion: Report of the 2019 Plant Science Research Network Workshop “Inclusivity in the Plant Sciences”

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier-free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well-being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now