Endothelial dysfunction in hypertension: pathophysiological mechanism or marker of cardiovascular risk?

Introduction Vascular endothelial production of nitric oxide (NO) plays an important role in the modulation of vessel tone and structure, protecting the vascular wall from atherosclerosis. In pathological conditions, however, the endothelium also produces pro-atherogenic substances (mainly reactive oxygen species), which inactivate NO. The Endothelial dysfunction, induced by reduced NO availability, is known to contribute to the development and progression of vascular damage. For this reason, endothelial function has been a major focus of cardiovascular research in the last few decades. Because NO has a very short half-life and its in vivo measurement is difficult, many researchers prefer to measure its biological activity, particularly the NO-dependent vasodilation, at the level of the coronary and peripheral circulation by endothelial stimuli. The most widely used technique involves measurement of brachial artery flow-mediated dilation. This test allows non-invasive evaluation of endothelium-dependent vasodilation in the peripheral macrocirculation induced by a mechanical stimulus (increase in shear stress caused by 5 minutes of forearm ischemia). The vasodilatatory response is reduced in the presence of major cardiovascular risk factors, particularly essential hypertension. Conclusions Studies conducted mainly in high-risk patients have demonstrated that endothelial dysfunction within the coronary or peripheral circulation is predictive of cardiovascular events (independently of classical risk factors). Drug therapy can improve endothelial function by increasing the availability of NO (a possible adjunctive benefit in terms of preventing vascular damage and improving the prognosis). Future studies will establish whether the evaluation of endothelial function by non-invasive, standardized, reproducible, low-cost techniques is an important test for cardiovascular risk stratification in clinical practice

Clinical outcomes of non-operative management and clinical observation in non-angioembolised hepatic trauma: A systematic review of the literature

Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE

Coordinated scheduling in a Virtual-RAN prototype with OpenAirInterface

The virtualized Radio Access Network (V-RAN) is a key technology for 5G networks. In this paper we present a live prototype of Virtual RAN implementing a Coordinated Scheduling algorithm enforced by a centralized coordinator. The 5G proof of concept, devised to improve the usage of radio resource and efficiency, is realized by exploiting open-source software to fully virtualize the LTE eNodeBs, and accommodates commercial terminals. We implemented two coordination algorithms: a simple static one for testing purposes, and a dynamic one appeared in [1]. Preliminary results show that coordination actually isolates the eNodeBs, reducing inter-cell interference

la disfunzione endoteliale nell ipertensione arteriosa meccanismo fisiopatologico o marcatore di rischio cardiovascolare

Summary Introduction Vascular endothelial production of nitric oxide (NO) plays an important role in the modulation of vessel tone and structure, protecting the vascular wall from atherosclerosis. In pathological conditions, however, the endothelium also produces pro-atherogenic substances (mainly reactive oxygen species), which inactivate NO. The Endothelial dysfunction, induced by reduced NO availability, is known to contribute to the development and progression of vascular damage. For this reason, endothelial function has been a major focus of cardiovascular research in the last few decades. Because NO has a very short half-life and its in vivo measurement is difficult, many researchers prefer to measure its biological activity, particularly the NO-dependent vasodilation, at the level of the coronary and peripheral circulation by endothelial stimuli. The most widely used technique involves measurement of brachial artery flow-mediated dilation. This test allows non-invasive evaluation of endothelium-dependent vasodilation in the peripheral macrocirculation induced by a mechanical stimulus (increase in shear stress caused by 5 minutes of forearm ischemia). The vasodilatatory response is reduced in the presence of major cardiovascular risk factors, particularly essential hypertension. Conclusions Studies conducted mainly in high-risk patients have demonstrated that endothelial dysfunction within the coronary or peripheral circulation is predictive of cardiovascular events (independently of classical risk factors). Drug therapy can improve endothelial function by increasing the availability of NO (a possible adjunctive benefit in terms of preventing vascular damage and improving the prognosis). Future studies will establish whether the evaluation of endothelial function by non-invasive, standardized, reproducible, low-cost techniques is an important test for cardiovascular risk stratification in clinical practice

Postnatal growth in a cohort of Sardinian intrauterine growth-restricted infants

Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (W), length (L) and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001). During the 1st year, 8 of 12 (70%) IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment

Mapping a Sex Hormone–Sensitive Gene Determining Female Resistance to Liver Carcinogenesis in a Congenic F344.BN-Hcs4 Rat

Hepatocellular carcinoma (HCC) is prevalent in human and rodent males. Hepatocarcinogenesis is controlled by various genes in susceptible F344 and resistant Brown Norway (BN) rats. B alleles at Hcs4 locus, on RNO16, control neoplastic nodule volume. We constructed the F344.BN-Hcs4 recombinant congenic strain (RCS) by introgressing a 4.41-cM portion of Hcs4 from BN strain in an isogenic F344 background. Preneoplastic and neoplastic lesions were induced by the ''resistant hepatocyte'' protocol. Eight weeks after initiation, lesion volume and positivity for proliferating cell nuclear antigen (PCNA) were much higher in lesions of F344 than BN rats of both sexes. These variables were lower in females than in males. Lesion volume and PCNA values of male RCS were similar to those of F344 rats, but in females corresponded to those of BN females. Carcinomatous nodules and HCC developed at 32 and 60 weeks, respectively, in male F344 and congenics and, rarely, in F344 females. BN and congenic females developed only eosinophilic/clear cells nodules. Gonadectomy of congenic males, followed by B-estradiol administration, caused a decrease in Ar expression, an increase in Er-a expression, and development of preneoplastic lesions comparable to those from BN females. Administration of testosterone to gonadectomized females led to Ar increase and development of preneoplastic lesions as in F344 males. This indicates a role of homozygous B alleles at Hcs4 in the determination of phenotypic patterns of female RCS and presence at Hcs4 locus of a high penetrance gene(s), activated by estrogens and inhibited/unaffected by testosterone, conferring resistance to females in which the B alleles provide higher resistance. (Cancer Res 2006; 66(21): 10384-90

Detection of post-traumatic abdominal pseudoaneurysms by CEUS and CT: A prospective comparative global study (the PseAn study)-study protocol

The success of non-operative management in trauma increased with the availability of new-generation CT scan machines, endoscopy, and angiography, becoming the standard of care in hemodynamically stable trauma patients with abdominal solid organ injuries, with a success rate of 78% to 98%. Post-traumatic pseudoaneurysms (PAs) can develop at any region of an injured artery and they may cause delayed bleeding in splenic or hepatic trauma, with an incidence in patients treated with NOM of 2%-27% and 1.2%-6.1% respectively. Diagnosis is made by angiography, contrast-enhanced computer tomography (CT), or Doppler Ultrasound (US) while the use of contrast-enhanced ultrasound (CEUS), has increased in recent years although few data are available about CEUS feasibility in the follow-up setting. The PseaAn study has been designed to assess the role of CEUS in the follow-up of abdominal trauma by defining its sensitivity, specificity and predictive values compared with abdominal CT scan. The PseAn study is a multi-centric international diagnostic cross-sectional study initiated by the Level I Trauma Center of the Niguarda Ca' Granda Hospital in Milan, Italy. To study the role of CEUS in detecting post-traumatic splenic, hepatic, and renal PAs compared with the gold standard of CT with intravenous contrast at different follow-up time points, and whether it can replace CT scan in the follow-up of solid organ injuries, patients with OIS III and above will undergo a follow-up with both a CEUS and CT scan to detect post-traumatic parenchymal pseudoaneurysm within two to five days from injury. The use of CEUS in the follow-up of abdominal trauma follow-up (particularly blunt trauma) has increased, to minimise the use of ionizing radiation and contrast media and encouraging results have been published during the last decade showing that CEUS is an accurate technique for evaluating traumatic lesions of solid abdominal organs. Conclusions We think that CEUS, which is underused worldwide, is a useful and safe tool that may replace CT scan in follow-up with the major advantage of reduced radiation. Our current study may give stronger evidence to support this view

Compliance with evidence-based clinical guidelines in the management of acute biliary pancreatitis: the MANCTRA-1 study protocol.

Despite existing evidence-based practice guidelines for the management of biliary acute pancreatitis (AP), the clinical compliance with recommendations is overall poor. Studies in this field have identified significant discrepancies between evidence-based recommendations and daily clinical practice. The most commonly reported gaps between clinical practice and AP guidelines include the indications for CT scan, need and timing of artificial nutritional support, indications for antibiotics, and surgical/endoscopic management of biliary AP. The MANCTRA-1 (coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis) study is aiming to identify the areas for quality improvement that will require new implementation strategies. The study primary objective is to evaluate which items of the current AP guidelines are commonly disregarded and if they correlate with negative clinical outcomes according to the different clinical presentations of the disease. We attempt to summarize the main areas of sub-optimal care due to the lack of compliance with current guidelines to provide the basis for introducing a number of bundles in AP patients' management to be implemented during the next years. The MANCTRA-1 study is an international multicenter, retrospective cohort study with the purpose to assess the outcomes of patients admitted to hospital with a diagnosis of biliary AP and the compliance of surgeons worldwide to the most up-to-dated international guidelines on biliary AP. ClinicalTrials.Gov ID Number: NCT04747990, Date: February 23, 2021. Protocol Version V2.2

Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line.

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis): The MANCTRA-1 international audit

Background/objectives: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines. Methods: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study. Categorical data were reported as percentages representing the proportion of all study patients or different and well-defined cohorts for each variable. Continuous data were expressed as mean and standard deviation. Differences between the compliance obtained in the four different subgroups were compared using the Mann-Whitney U, Student's t, ANOVA or Kruskal-Wallis tests for continuous data, and the Chi-square test or the Fisher's exact test for categorical data. Results: Complete data were available for 5275 patients. The most commonly discordant gaps between daily clinical practice and recommendations included the optimal timing for the index CT scan (6.1%, χ2 6.71, P = 0.081), use of prophylactic antibiotics (44.2%, χ2 221.05, P < 0.00001), early enteral feeding (33.2%, χ2 11.51, P = 0.009), and the implementation of early cholecystectomy strategies (29%, χ2 354.64, P < 0.00001), with wide variability based on the admitting speciality. Conclusions: The results of this study showed an overall poor compliance with evidence-based guidelines in the management of ABP, with wide variability based on the admitting speciality. Study protocol registered in ClinicalTrials.Gov (ID Number NCT04747990)