C-peptide: a predictor of cardiovascular mortality in subjects with established atherosclerotic disease

Aim: Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease. Methods: We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events. Results: We performed a mean follow-up of 56months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p<0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors. Conclusion: C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker

Nanoprobes to interrogate nonspecific interactions in lipid bilayers: from defect-mediated adhesion to membrane disruption

When a lipid membrane approaches a material/nanomaterial, nonspecific adhesion may occur. The interactions responsible for nonspecific adhesions can either preserve the membrane integrity or lead to its disruption. Despite the importance of the phenomenon, there is still a lack of clear understanding of how and why nonspecific adhesions may originate different resulting scenarios and how these interaction scenarios can be interrogated. This work aims at bridging this gap by investigating the interplay between cationic electrostatic and hydrophobic interactions in modulating the membrane stability during nonspecific adhesion phenomena. Here, the stability of the membrane has been studied employing anisotropic nanoprobes in zwitterionic lipid membranes with the support of coarse-grained molecular dynamics simulations to interpret the experimental observations. Lipid membrane electrical measurements and nanoscale visualization in combination with molecular dynamics simulations revealed the phenomena driving nonspecific adhesion. Any interaction with the lipidic bilayer is defect-mediated involving cationic electrostatically-driven lipid extractions and hydrophobicallydriven chains protrusion, whose interplay determines the existence of a thermodynamic optimum for the membrane structural integrity. These findings unlock unexplored routes to exploit nonspecific adhesion in lipid membranes. The proposed platform can act as a straightforward probing tool to locally interrogate interactions between synthetic materials and lipid membranes for the design of antibacterials, antivirals, and scaffolds for tissue engineering

GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC

IL-6 Levels Influence 3-Month All-Cause Mortality in Frail Hospitalized Older Patients

The multidimensional prognostic index (MPI) is a sensitive and specific prognosis estimation tool that accurately predicts all-cause mortality in frail older patients. It has been validated to assess the risk of 1-month to 2-year mortality in frail older patients during hospitalization and after hospital discharge. However, whether the MPI is a valid prognostic tool for follow-up periods of different lengths remains to be validated. To this end, we followed up 80 hospitalized patients (female=37, male 43) at least 75 years of age (mean age=82.6±4.4, range=75-94 years) to assess the 3-month all-cause mortality (mean follow-up=61.0 ± 31.7 months [range 4-90 days]). Accordingly, patients were subdivided into low (MPI-1, score 0-0.33), moderate (MPI-2, score 0.34-0.66) and high (MPI-3, score 0.67-1) mortality risk classes. Moreover, baseline biochemical, inflammatory and metabolic parameters, as well as anamnestic and clinical characteristics, were obtained. Although the MPI-3 score was significantly associated with 3-month all-cause mortality in univariate analysis (HR=5.79, 95%CI=1.77-18.92, p=0.004), a multivariate model indicated that only low albumin (HR=0.33, 95%CI=0.16-0.68, p=0.003) and high IL6 (HR=1.01, 95%CI=1.00-1.02, p=0.010) levels were significantly associated with 3-month all-cause mortality. In conclusion, we suggest that measurement of IL6 as well as albumin, rather than the MPI score, may help in providing tailored therapeutic interventions to decrease short term mortality in older hospitalized individuals

Pathology reporting in neuroendocrine neoplasms of the digestive system: everything you always wanted to know but were too afraid to ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Income level and chronic ambulatory care sensitive conditions in adults: a multicity population-based study in Italy

<p>Abstract</p> <p>Background</p> <p>A relationship between quality of primary health care and preventable hospitalizations has been described in the US, especially among the elderly. In Europe, there has been a recent increase in the evaluation of Ambulatory Care Sensitive Conditions (ACSC) as an indicator of health care quality, but evidence is still limited. The aim of this study was to determine whether income level is associated with higher hospitalization rates for ACSC in adults in a country with universal health care coverage.</p> <p>Methods</p> <p>From the hospital registries in four Italian cities (Turin, Milan, Bologna, Rome), we identified 9384 hospital admissions for six chronic conditions (diabetes, hypertension, congestive heart failure, angina pectoris, chronic obstructive pulmonary disease, and asthma) among 20-64 year-olds in 2000. Case definition was based on the ICD-9-CM coding algorithm suggested by the Agency for Health Research and Quality - <it>Prevention Quality Indicators</it>. An area-based (census block) income index was used for each individual. All hospitalization rates were directly standardised for gender and age using the Italian population. Poisson regression analysis was performed to assess the relationship between income level (quintiles) and hospitalization rates (RR, 95% CI) separately for the selected conditions controlling for age, gender and city of residence.</p> <p>Results</p> <p>Overall, the ACSC age-standardized rate was 26.1 per 10.000 inhabitants. All conditions showed a statistically significant socioeconomic gradient, with low income people being more likely to be hospitalized than their well off counterparts. The association was particularly strong for chronic obstructive pulmonary disease (level V low income vs. level I high income RR = 4.23 95%CI 3.37-5.31) and for congestive heart failure (RR = 3.78, 95% CI = 3.09-4.62). With the exception of asthma, males were more vulnerable to ACSC hospitalizations than females. The risks were higher among 45-64 year olds than in younger people.</p> <p>Conclusions</p> <p>The socioeconomic gradient in ACSC hospitalization rates confirms the gap in health status between social groups in our country. Insufficient or ineffective primary care is suggested as a plausible additional factor aggravating inequality. This finding highlights the need for improving outpatient care programmes to reduce the excess of unnecessary hospitalizations among poor people.</p

Commentary: Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management

In the issue of March 2021, Lenschow et al. reported the case of a 46-year-old woman with recurrent, programmed death-ligand-1 (PD-L1) negative, tumor mutational burden (TMB)-high parathyroid carcinoma (PC), who showed stable disease as her best response on imaging, and a three-fold drop in PTH after treatment with intravenous pembrolizumab. Given the remarkable results obtained by Lenschow et al. with the anti-PD-1 agent pembrolizumab in the above-mentioned case, we performed an extensive search for possible further relevant data sources, including a) full published articles in international online databases (PubMed, Web of Science, Scopus, and Embase); b) preliminary reports in selected international meeting abstract repositories (American Society of Clinical Oncology, ASCO; European Neuroendocrine Tumor Society, ENET; European Society for Medical Oncology, ESMO); c) registered clinical trials in the U.S. National Institutes of Health registry of clinical trials (http://clinicaltrials.gov) and in any primary register of the WHO International Clinical Trials Registry Platform (ICTRP)

Fast-muscle contraction as a proxy to embodiment and BCI control in tetraplegia: an EEG study in immersive virtual reality

Embodiment with an avatar perceived in first-person (1PP) perspective is crucial in eliciting Medial-Frontal Theta activity contingent upon detection of the avatar's action errors. In the present study we devised a new paradigm for inducing embodiment and neurophysiological correlates of error detection in profoundly de-afferented/de-efferented patients. The paradigm consisted in asking the patient to perform a fast and rapid contraction of a residual muscle (monitored through ElectroMiografic-EMG burst activation ) to activate a cascade of events ultimately ending in increased sense of agency and ownership of the acting virtual arm

The role of affective awareness in a social categorization task: behavioural and autonomic data

Affective neuroscience research posits that non-conscious stimuli evoke emotion states and physiological indexes also when individuals are not visually aware of them. In this study we tested in 34 Italian participants whether subliminal and supraliminal affective priming may influence the attribution of faces to a social group. Participants' face temperature (peri-orbital region and nasal tip) during the task was measured by means of functional infrared thermal imaging (fITI). This technique allows skin temperature recording by tracking changes in facial temperature with high thermal resolution. The emotional visual stimuli used for the affective priming were taken from the International Affective Picture System and the neutral faces employed in the social categorization task were taken from three validated face sets. To prevent visual stimuli to be consciously perceived, we employed the forward and backward masking technique: the target image was presented for 33 ms and it was preceded and followed by visual masks created by scrambling the target itself. During the supraliminal block the target image was presented for 500 ms. In the subsequent social categorization task, participants were asked to report whether the neutral face belonged to an in-group (i.e., Italian) vs out-group (i.e., Romanian) individual. We fit behavioral and thermal data in a mixed model logistic regression predicting the probability of categorizing the face as in/out-group. A significant two-way interaction between negative valence and temperature (200-600 ms time bin) was present. In the negative subliminal condition the increase in orbital temperature - indexing the engagement of the ANS sympathetic division - predicted out-group categorization, while its decrease - indexing the engagement of the ANS para-sympathetic division - predicted in-group categorization. By contrast, in the negative supraliminal condition, the increase in orbital and nose temperature predicted the categorization of faces as in-group, while its decrease predicted out-group categorization. In keeping with assimilation and contrast effects in priming research, target categorization in the subliminal block was valence-driven, whereas in the supraliminal block, target categorization was opposite respect to the valence of the prime. As an emotional regulation index, we computed the difference in orbital temperature when categorizing the face as out-group vs in-group in the negative supraliminal condition. The difference was negatively correlated with the frequency of in-group choices suggesting that higher sympathetic activity may underpin the aversion to include strangers in one's own social group. Inclusion behavior seems to be affected by differences in emotion regulation: the tendency to transfer priming-driven affective reactions to unrelated social decisions is in fact more pronounced in individuals who show stronger increases of peri-orbital temperature when facing threat-related stimuli