Mapping Protein Structure Changes with Cysteine Labeling Kinetics by Mass Spectrometry

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Effective nonapical left ventricular pacing with quadripolar leads for cardiac resynchronization therapy

Background: Current guidelines recommend avoiding apical left ventricular (LV) pacing for cardiac resynchronization therapy (CRT). Aims: We investigated the feasibility of nonapical pacing with the current quadripolar LV lead technology. Methods: We analyzed consecutive patients who received CRT with an LV quadripolar lead. The post­­implantation position of each electrode of the LV lead was designated as basal, mid, or apical. The pacing capture threshold (PCT) and phrenic nerve stimulation (PNS) threshold were assessed for each electrode. Results: We enrolled 168 patients. A total of 8 CRT defibrillators were from Biotronik (with Sentus OTW QP leads), 98 were from Boston Scientific (with 21 Acuity X4 Spiral and 77 Acuity X4 Straight leads), and 62 from St. Jude Medical (with Quartet leads). The median (interquartile range) number of electrodes at nonapical segments per patient was 3 (1–4) with Biotronik Sentus leads, 4 (3–4) with spiral ­design Boston Scientific leads, 4 (3–4) with straight Boston Scientific leads, and 3 (3–4) with St. Jude Medical Quartet leads (P = 0.045). Three patients (38%) with Biotronik Sentus leads, 21 (100%) with spiral ­design Boston Scientific leads, 69 (90%) with straight ­design Boston Scientific leads, and 49 (79%) with St. Jude Medical Quartet leads (P < 0.001) had at least 1 electrode located at nonapical segments linked with a PNS ­PCT safety margin of more than 2 V. During the 6­month follow ­up, PNS was detected in 4 patients and was eliminated with reprogramming. No significant changes in PCT were detected during follow ­up. Conclusions: Quadripolar leads allowed nonapical pacing with acceptable electrical parameters in the majority of CRT recipients, although differences were found among the currently available devices

MORFEO enters final design phase

MORFEO (Multi-conjugate adaptive Optics Relay For ELT Observations, formerly MAORY), the MCAO system for the ELT, will provide diffraction-limited optical quality to the large field camera MICADO. MORFEO has officially passed the Preliminary Design Review and it is entering the final design phase. We present the current status of the project, with a focus on the adaptive optics system aspects and expected milestones during the next project phase

GRASP65 and GRASP55 Sequentially Promote the Transport of C-terminal Valine-bearing Cargos to and through the Golgi Complex

The Golgi matrix proteins GRASP65 and GRASP55 have recognized roles in maintaining the architecture of the Golgi complex, in mitotic progression and in unconventional protein secretion whereas, surprisingly, they have been shown to be dispensable for the transport of commonly used reporter cargo proteins along the secretory pathway. However, it is becoming increasingly clear that many trafficking machineries operate in a cargo-specific manner, thus we have investigated whether GRASPs may control the trafficking of selected classes of cargo. We have taken into consideration the C-terminal valine-bearing receptors CD8alpha and Frizzled4 that we show bind directly to the PSD95-DlgA-zo-1 (PDZ) domains of GRASP65 and GRASP55. We demonstrate that both GRASPs are needed sequentially for the efficient transport to and through the Golgi complex of these receptors, thus highlighting a novel role for the GRASPs in membrane trafficking. Our results open new perspectives for our understanding of the regulation of surface expression of a class of membrane proteins, and suggests the causal mechanisms of a dominant form of autosomal human familial exudative vitreoretinopathy that arises from the Frizzled4 mutation involving its C-terminal valine

Stricter criteria for left bundle branch block diagnosis do not improve response to CRT

BACKGROUND: Cardiac resynchronization therapy (CRT) has proved to be effective in patients with heart failure and left bundle branch block (LBBB). Recently, new ECG criteria have been proposed for the diagnosis of LBBB. These criteria are stricter than the current American Heart Association (AHA) criteria. We assessed the rate of echocardiographic response to CRT in patients with traditional LBBB versus patients who met the new criteria (strict LBBB). METHODS: Consecutive patients undergoing CRT were enrolled in the CRT MORE registry. Patients with no-LBBB QRS morphology according to AHA criteria, atrial fibrillation, right bundle branch block and right ventricular pacing were excluded. Strict LBBB was defined as: QRS 65140ms for men and 65130ms for women, QS or rS in V1-V2, mid-QRS notching or slurring in 652 contiguous leads. Patients showing a relative decrease of 6515% in left ventricular end-systolic volume (LVESV) at 12 months were defined as responders. RESULTS: Among 335 patients with LBBB, 131 (39%) had strict LBBB. Patients with and without strict LBBB showed comparable baseline characteristics, except for QRS duration (166\ub120ms vs 152\ub125ms, p<0.001). On 12-month evaluation, 205 patients (61%) were responders; 85/131 (65%) had strict LBBB and 120/204 (59%) had traditional LBBB (p = 0.267). On multivariate analysis, a history of atrial fibrillation, larger LVESV, and the presence of mid-QRS notching in 651 lead (OR 2.099; 95% CI 1.061 to 4.152, p = 0.033) were independently associated with echocardiographic response. CONCLUSIONS: Stricter definition of LBBB did not improve response to CRT in comparison to the current AHA definition

Patient acceptance of subcutaneous versus transvenous defibrillator systems: a multi-center experience

Background The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an effective alternative to the transvenous ICD. No study has yet compared S-ICD and transvenous ICD by assessing patient acceptance as a patient-centered outcome. Objective To evaluate the patient acceptance of the S-ICD and to investigate its association with clinical and implantation variables. In patients with symptomatic heart failure and reduced ejection fraction (HFrEF), the acceptance of the S-ICD was compared with a control group of patients who received a transvenous ICD. Methods Patient acceptance was calculated with the Florida Patient Acceptance Survey (FPAS) which measures four factors: return to function (RTF), device-related distress (DRD), positive appraisal (PA), and body image concerns (BIC). The survey was administered 12 months after implantation. Results 176 patients underwent S-ICD implantation. The total FPAS and the single factors did not differ according to gender, body habitus, or generator positioning. Patients with HFrEF had lower FPAS and RTF. Younger patients showed better RTF (75 [56-94] vs. 56 [50-81], p = .029). Patients who experienced device complications or device therapies showed higher DRD (40 [35-60] vs. 25 [10-50], p = .019). Patients with HFrEF receiving the S-ICD had comparable FPAS, RTF, DRD, and BIC to HFrEF patients implanted with the transvenous ICD while exhibited significantly better PA (88 [75-100] vs. 81 [63-94], p = .02). Conclusions Our analysis revealed positive patient acceptance of the S-ICD, even in groups at risk of more distress such as women or patients with thinner body habitus, and regardless of the generator positioning. Among patients receiving ICDs for HFrEF, S-ICD was associated with better PA versus transvenous ICD

Implantable defibrillator-detected heart failure status predicts atrial fibrillation occurrence

BACKGROUND In heart failure (HF) patients, atrial fibrillation (AF) is associated with a worse prognosis. Implantable cardioverter-defibrillator (ICD) diagnostics allow continuous monitoring of AF and are equipped with algorithms for HF moni-toring. OBJECTIVE We evaluated the association between the values of the multisensor HF HeartLogic index and the incidence of AF, and as-sessed the performance of the index in detecting follow-up periods of significantly increased AF risk. METHODS The HeartLogic feature was activated in 568 ICD pa-tients. Median follow-up was 25 months [25th-75th percentile (15-35)]. The HeartLogic algorithm calculates a daily HF index and identifies periods of IN-alert state on the basis of a configurable threshold. The endpoints were daily AF burden &gt;= 5 minutes, &gt;= 6 hours, and &gt;= 23 hours. RESULTS The HeartLogic index crossed the threshold value 1200 times. AF burden &gt;= 5 minutes/day was documented in 183 patients (32%), &gt;= 6 hours/day in 118 patients (21%), and &gt;= 23 hours/day in 89 patients (16%). The weekly time of IN-alert state was independently associated with AF burden &gt;= 5 minutes/day (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.22- 3.13; P 5 .005), &gt;= 6 hours/day (HR 2.66; 95% CI 1.60-4.44; P &lt;.001), and &gt;= 23 hours/day (HR 3.32; 95% CI 1.83-6.02; P &lt;.001), after correction for baseline confounders. Comparison of the episode rates in the IN-alert state with those in the OUT -of-alert state yielded HR ranging from 1.57 to 3.11 for AF burden from &gt;= 5 minutes to &gt;= 23 hours. CONCLUSIONS The HeartLogic alert state was independently asso-ciated with AF occurrence. The intervals of time defined by the algo-rithm as periods of increased risk of HF allow risk stratification of AF according to various thresholds of daily burden

SGLT2 breast expression could affect the cardiovascular performance in pre-menopausal women with fatty vs. non fatty breast via over-inflammation and sirtuins' down regulation

Objectives: To evaluate the expression of sodium-glucose transporter 2 (SGLT2), inflammatory cytokines, and sirtuins in breast fat tissue at baseline, and serum cytokines of fatty vs. non-fatty pre-menopausal women at baseline, and at 12 months of follow-up. To correlate SGLT2/cytokines/sirtuins expression to clinical variables, and their changes (Δ) at follow-up, as intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. Background: Pre-menopausal women with the lowest breast fat density (fatty breast) vs. higher breast fat density (non-fatty breast) are a high-risk population for cardiovascular diseases and worse prognosis. Methods: We analyzed SGLT2/cytokines/sirtuins of excised fatty breasts of fatty vs. non-fatty pre-menopausal women. We correlated SGLT2/cytokines/sirtuins to Δ IMT, Δ LVM, Δ LVEF, and Δ MPI, and normal cardiac performance (NCP) at 1 year of follow-up. Results: fatty vs. non-fatty breast over-expressed SGLT2/inflammatory cytokines, with lowest values of sirtuins (p&lt;0.05). We found a direct correlation between SGLT2 (R2 0.745), TNFα (R2 0.262), and ΔMPI (p&lt;0.05), and an inverse correlation between breast density (R2 -0.198), SIRT-3 (R2-0.181), and ΔMPI (p&lt;0.05). Fatty breast (0.761, CI 95% [0.101-0.915]), SGLT2 (0.812, CI 95% [0.674-0.978]) and SIRT-3 (1.945, CI 95% [1.201-3.148]) predicted NCP at 1 year of follow-up. Conclusions: fatty vs. non-fatty breast women over-expressed SGLT2/inflammatory cytokines, and down-regulated breast sirtuins. SGLT2/inflammatory cytokines expression and inversely the tissue sirtuin 3 (tSIRT3) and breast percentage density linked to ΔMPI at 1 year of follow-up. Fatty breast and SGLT2 inversely predicted NCP; SIRT-3 increased the probability of NCP at 1 year of follow-up