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Background: Clinical reasoning (CR) is fundamental in medical education. However, the Italian curriculum has not incorporated a structured CR format yet. Therefore, we introduced the Clinical Case Discussions (CCD), to medical students attending the University of Bologna as a tool for developing CR abilities. CCDs are a case-based peer-teaching format, simulating the diagnostic process using published patient cases. Methods: Students of all clinical years of the University of Bologna Medical School were invited to voluntarily participate in a two-day CCD training program. They completed pre- and post-training questionnaires assessing their expectations before and impressions after the training and comparing learning outcomes to their usual classes. Results: Twenty-one students participated in this pilot program. Before the training, more than half of the participants expressed either interest or a strong interest in all proposed learning objectives. Afterward, 84.6% of the students stated that the training much exceeded (63.5%) or exceeded (23.1%) their expectations considering its utility for their future medical activities. A total of 92.3% strongly agreed (84.6%) or agreed (7.7%) to have improved their CR. Conclusions: Although this pilot program had some intrinsic limitations, the students’ positive feedback on this CCD format (combining the benefits of case-based learning and peer teaching) encourages further research on its potential role in the Italian curriculum.

Abstract The energy harvesting capability of a graded metamaterial is maximised via reinforcement learning (RL) under realistic excitations at the microscale. The metamaterial consists of a waveguide with a set of beam-like resonators of variable length, with piezoelectric patches, attached to it. The piezo-mechanical system is modelled through equivalent lumped parameters determined via a general impedance analysis. Realistic conditions are mimicked by considering either magnetic loading or random excitations, the latter scenario requiring the enhancement of the harvesting capability for a class of forcing terms with similar but different frequency content. The RL-based optimisation is empowered by using the physical understanding of wave propagation in a such local resonance system to constrain the state representation and the action space. The procedure outcomes are compared against grading rules optimised through genetic algorithms. While genetic algorithms are more effective in the deterministic setting featuring the application of magnetic loading, the proposed RL-based proves superior in the inherently stochastic setting of the random excitation scenario.

Abstract First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver’s disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose–response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43–82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3–6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin’s concordance correlation coefficients (ρ c and C b), Pearson’s coefficient correlation (ρ), and Bland–Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46–1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρ c = 0.703, C b = 0.969) with good agreement (mean difference: − 4.93 ± 218.3 Gy, 95%LOA: − 432.8–422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρ c = 0.998, C b = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: − 4.05 ± 55.9 Gy; 95%LOA: − 113.7–105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (− 70.9 ± 158.9 Gy; 95%LOA: − 382.3–240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρ c = 0.713, C b = 0.903 vs without correction: ρ = 0.395, ρ c = 0.244, C b = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: − 375.4–673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρ c = 0.852, C b = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose–response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

Abstract Here, we present the results related to a new unique terrestrial ecosystem found in an englacial hypersaline brine found in Northern Victoria Land (Antarctica). Both the geochemistry and microbial (prokaryotic and fungal) diversity revealed an unicity with respect to all the other known Antarctic brines and suggested a probable ancient origin mainly due a progressive cryoconcentration of seawater. The prokaryotic community presented some peculiarities, such as the occurrence of sequences of Patescibacteria (which can thrive in nutrient-limited water environments) or few Spirochaeta, and the presence of archaeal sequences of Methanomicrobia closely related to Methanoculleus, a methanogen commonly detected in marine and estuarine environments. The high percentage (35%) of unassigned fungal taxa suggested the presence of a high degree of undiscovered diversity within a structured fungal community (including both yeast and filamentous life forms) and reinforce the hypothesis of a high degree of biological uniqueness of the habitat under study.

Abstract Background Pulmonary arterial hypertension is a progressive, debilitating condition characterized by increased resistance in the pulmonary arterial circulation. Current treatments for pulmonary arterial hypertension include endothelin receptor antagonists such as bosentan, sitaxentan, ambrisentan, macitentan, and oral prostacyclin receptor agonists such as selexipag. Endothelin receptor antagonists have been associated with liver injury, while hepatotoxicity was not reported for selexipag. Although genetic variability has been indisputably associated with variability in drug response, no study has been designed until now to assess its effects on the pharmacokinetics of endothelin receptor antagonists or selexipag. Case presentation We report the case of a 58-year-old female Caucasian patient with a dramatic increase in plasma levels of transaminases after treatment with macitentan and selexipag, drugs whose risk of causing liver injury has so far been considered limited. After therapy discontinuation, plasma levels of transaminases returned to baseline, thus suggesting a role of these drugs in the observed hepatotoxicity. After pharmacological counseling, we decided to introduce ambrisentan for the patient’s treatment. After 7 months of treatment, no liver injury has been reported. To evaluate the role of genetic factors in the observed hepatotoxicity, we genotyped the patient for single-nucleotide polymorphisms previously associated with macitentan, ambrisentan, or selexipag metabolism. We found a genetic profile associated with a poor metabolizer (PM) phenotype for CYP2C8 and CYP2C9, key enzymes for elimination of both macitentan and selexipag. The reported results suggest that an allelic profile associated with low activity for CYP2C8 and CYP2C9 enzyme could be a potential risk factor for macitentan and selexipag-induced liver injury and could provide a possible marker for early identification of subjects at higher risk of developing hepatotoxicity. Conclusions A multidisciplinary approach based on clinical evaluation, as well as pharmacological counseling and evaluation of the patient’s genetic profile, might be useful for identification of patients with a high chance of drug-induced liver injury, avoiding unnecessary risks in therapy selection and prescription.

During the COVID-19 outbreak, the risk of depression has increased for pregnant women and especially for first-time mothers-to-be. Pre-COVID-19 literature showed that depression is negatively linked to mental representations during pregnancy. This pilot study explored the difference in depressive symptoms and maternal representations style in primiparous and multiparous pregnant women during the outbreak of COVID-19 (2020-2021). 25 women (14 primiparous, 11 multiparous) were recruited in their last trimester of pregnancy. Participants responded to the Edinburgh Postnatal Depression Scale (EPDS) and Interview for Maternal Representations during Pregnancy (Intervista sulle Rappresentazioni Materne in Gravidanza – IRMAG). Results showed that primiparous women presented higher depressive symptoms than multiparous ones. Moreover, primiparous women reported lower richness of perception (p = 0.008), openness to change (p = 0.035) and dominance of fantasies (p = 0.000) in maternal representation and, globally, more restricted representations (71.4%) than multiparous ones (18.2%) (p = 0.020). Mental representations were related to the level of depression, with integrated representations being associated with lower depression than restricted and ambivalent ones (p = 0.001). A preventive intervention to support primiparous pregnant women during future pandemics would be necessary in particular to avoid negative repercussions also in the post-partum experience. This paper is part of the “Pediatric Psychology and Related Issues” Section (Sezione “Psicologia Pediatrica e Dintorni”) by S.I.P.Ped. (Italian Society of Pediatric Psychology, Società Italiana di Psicologia Pediatrica).

Desde tiempos inmemoriales los habitantes de este planeta hemos tenido una clara tendencia a organizarnos siguiendo una pauta más o menos jerárquica. No es el objeto de este escrito analizar las causas, ni siquiera indagar en los orígenes de tal manera de proceder Pensadores como Ken Wilber o, en el terreno de la gestión de empresas, Gary Hamel, han analizado en profundidad el fenómeno y sus implicaciones. El objeto es este texto es preguntarnos si dicha forma de organización sigue vigente y, en paralelo, cuestionar su viabilidad de futuro.

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy, considered a rare cause of coronary artery disease. Although familial cases have been described, no specific gene association has been detected so far. When the coronary vessels are involved, the main clinical scenarios are stable angina, acute coronary syndromes, left ventricular dysfunction, and sudden death. Specific clinical and angiographic findings may suggest this as the underlying disease, but certain diagnosis histological. The involvement of the lower and upper limbs is unusual; however, it may have decisive clinical implications for the most appropriate revascularization method and the selection of the arterial graft to be used.

Abstract Immune response to biologics treatment, while widely reported, yet fails to correlate with clinical outcomes and assay to assay comparison is often not possible. Hence, we developed a new peptide based-detection assay to stratify pediatric patients with juvenile idiopathic arthritis (JIA) or chronic non-infectious uveitis (CNU) and monitor anti-drug antibodies (ADAbs) formed as part of an immune response to treatment with the fully human monoclonal therapeutic antibody Adalimumab. Adalimumab derived synthetic peptides were optimized for maximum immunogenicity and were tested by SP-ELISA on a development cohort of 18 JIA and CNU treated patients. The two best performing peptides able to differentiate patient groups were selected for evaluation with a larger scale ELISA testing on a total of 29 sera from pediatric patients with JIA or CNU. The results of this peptide-based assay were compared to an in-house developed SPR biosensor ADAbs assay and a commercially available bridging ELISA. The first peptide, termed HC3, was able to positively detect ADAbs in 7 out of the 29 sera, while the second peptide, called LC3, was able to detect ADAbs in 11 out of 29 sera in the evaluation group. Following statistical data evaluation, it has been found that the detection of ADAbs using the peptide-based ELISA assay positively correlates with disease progression and remission. Two synthetic peptides derived from Adalimumab may provide a beneficial tool to clinicians for monitoring patient response to such treatment and taking informed decisions for treatment alternatives.

Abstract Nanoplastic particulates (pNP) are widely considered as being potentially harmful to the environment and living organisms while also being technically difficult to detect and identify in the presence of biological matrices. In this study, we describe a method for the extraction and subsequent Raman analysis of pNP present in the tissues of salt-water mussels. The process combines a step of enzymatic digestion/filtering to eliminate the biological matrix with a detection/identification procedure, which uses a micro-machined surface, composed of arrays of cavities with well-defined sub-micron depths and diameters. This sensor surface, exploits capillary forces in a drying droplet of analyte solution to drive the self-assembly of suspended nanoparticles into the cavities leaving the individual particles isolated from each other over the surface. The resulting array, when analysed using confocal Raman microscopy, permits the size selective analysis of the individual sub-micron pNP trapped in the cavities structure.

Abstract In patients with PLSVC, the use of an active fixation lead (like the Medtronic “Attain Stability”) on the coronary sinus can lead to a successful and safe cardiac resynchronization, facilitating its positioning with a low long‐term displacement rate.

Abstract Background The Coronavirus Disease 19 (COVID-19) pandemic brought significant disruption to in-hospital medical training. Virtual reality simulating the clinical environment has the potential to overcome this issue and can be particularly useful to supplement the traditional in-hospital medical training during the COVID-19 pandemic, when hospital access is banned for medical students. The aim of this study was to assess medical students’ perception on fully online training including simulated clinical scenarios during COVID-19 pandemic. Methods From May to July 2020 when in-hospital training was not possible, 122 students attending the sixth year of the course of Medicine and Surgery underwent online training sessions including an online platform with simulated clinical scenarios (Body Interact™) of 21 patient-based cases. Each session focused on one case, lasted 2 h and was divided into three different parts: introduction, virtual patient-based training, and debriefing. In the same period, adjunctive online training with formal presentation and discussion of clinical cases was also given. At the completion of training, a survey was performed, and students filled in a 12-item anonymous questionnaire on a voluntary basis to rate the training quality. Results were reported as percentages or with numeric ratings from 1 to 4. Due to the study design, no sample size was calculated. Results One hundred and fifteen students (94%) completed the questionnaire: 104 (90%) gave positive evaluation to virtual reality training and 107 (93%) appreciated the format in which online training was structured. The majority of participants considered the platform of virtual reality training realistic for the initial clinical assessment (77%), diagnostic activity (94%), and treatment options (81%). Furthermore, 97 (84%) considered the future use of this virtual reality training useful in addition to the apprenticeship at patient’s bedside. Finally, 32 (28%) participants found the online access difficult due to technical issues. Conclusions During the COVID-19 pandemic, online medical training including simulated clinical scenarios avoided training interruption and the majority of participant students gave a positive response on the perceived quality of this training modality. During this time frame, a non-negligible proportion of students experienced difficulties in online access to this virtual reality platform.

Abstract Background The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF−), including dermoscopic findings of melanomas and dysplastic nevi. Methods we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available. Results After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF−. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF−). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF− patients, whose most prevalent pattern was the multicomponent. Conclusions MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF− patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.

Endovascular interventions (EVI) are increasingly performed as minimally-invasive alternatives to surgery and have many advantages, including a decreased need for general anesthesia. However, EVI can be stressful for patients and often lead to anxiety and pain related to the procedure. The use of local anesthetics, anxiolytics, and analgesic drugs can help avoid general anesthesia. Nevertheless, these drugs have potential side effects. Alternative nonpharmacological therapies can improve patients’ experience during conscious interventions and reduce the need for additional medications. The added value of virtually augmented self-hypnosis (VA-HYPO) and its potential to reduce pain and anxiety during peripheral and visceral arterial and venous EVI is unknown. This is a prospective two-arm trial designed to randomize 100 patients in two groups according to the use or not of VA-HYPO during peripheral EVI as a complementary nonpharmacological technique to improve patient comfort. The main objective is to compare per-procedural anxiety, and the secondary aim is to compare the rated per-procedural pain in both groups. The potential significance is that VA-HYPO may improve patients’ experience during peripheral and visceral arterial and venous EVI and other minimally invasive interventions performed under local anesthesia. Trial registration: Our study is registered on clinicaltrials.gov, with trial registration number: NCT04561596.

A real-world analysis among the Italian population has been carried out to estimate the number of atrial fibrillation (AF) patients undergoing catheter ablation and to evaluate their clinical outcome and economic burden. A retrospective analysis on administrative Italian databases has been performed. Between January 2011 and December 2019, all patients diagnosed with AF were considered and those undergoing catheter ablation were identified. Overall, 3084 (3.54%) of AF patients with at least one catheter ablation were included (mean age 63.2, 67.3% males). A significant decrease in the use of AF-related medications and in hospitalizations, mainly related to AF and heart failure, was observed during the 3-year post-ablation period. The average total cost per patient during the 1-year before ablation period was significantly higher compared to the 1-year post-ablation cost (EUR 5248 vs. 4008, respectively; p < 0.001). After propensity score matching, the overall mortality of patients who underwent ablation was significantly lower compared to that assessed in patients not treated with the procedure (9.386/1000 vs. 23.032/1000 person-year, respectively; p < 0.001). Moreover, the mean total costs were significantly higher in patients who did not undergo ablation compared to those who received ablation (EUR 5516 vs. 4008, respectively; p < 0.001). This real-world data analysis shows that in Italy, although catheter ablation is performed in a minority of AF patients, it is associated with significantly better post-procedure clinical outcomes and a significant reduction in healthcare-related costs.

Usnic acid (UA) is one of the most abundant and common metabolites of lichens, known for its numerous pharmacological properties. Nevertheless, it presents some criticalities that severely limit its use in therapy: poor solubility in water and significant hepatotoxicity. Soluplus and Solutol HS15 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) were employed to develop polymeric micelles (UA–PM). The chemical and physical properties of the system were characterized, including the size, homogeneity, zeta potential, critical micellar concentration (CMC), encapsulation efficiency (EE%), and in vitro release. The freeze-drying process was considered to prevent agglomeration and improve the stability of the formulation. The stability of the micelles and the freeze-dried product (UA–PML) was also evaluated. The anti-migratory activity of UA and UA–PM was evaluated in human neuroblastoma SH-SY5Y cells using the wound healing assay. Their effect on the activity of metalloproteinases (MMP)-2/9 involved in the migration process of cells was verified by gelatin zymography. The optimized UA–PM contained Soluplus, Solutol HS15, and TPGS in a 1:4:0.5 weight ratio and increased the aqueous solubility to about 150-fold solubilized, solubilizing 0.5 mg/mL of UA. UA–PM has a small size (45.39 ± 0.31 nm), a polydispersity index (PDI) of 0.26 ± 0.01, and an EE% of 82.13 ± 5.57%. The colloidal dispersion was stable only for 9 days at 4 °C, while the freeze-drying process improved the stability for up to 30 days. UA was released for a prolonged period during the in vitro release study. The in vitro cell-based experiments showed that UA–PM (0.2 µg/mL) inhibited SH-SY5Y cell migration and the gelatinolytic activity of MMP-2/9 in culture media, while free UA at the same concentration exerted no biological activity. This study demonstrates that polymeric micelles are an excellent formulation for UA to manifest inhibitory action on neuroblastoma cell migration.

Abstract Late‐onset migration of pacing leads in the left hemithorax is a rare but potentially life‐threatening complication. Radiological examinations are required to detect any involvement of either left ventricle or lung parenchyma, prompting immediate surgical extraction in this setting. Identification of high‐risk patients is mandatory to prevent this complex iatrogenic complication.

Through this structured review of the published literature, we aimed to provide an up-to-date description of strategies (human-related) and tools (mainly from the digital field) facilitating the appropriateness of drug use in older adults. The evidence of each strategy and tool’s effectiveness and sustainability largely derives from local and heterogeneous experiences, with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve appropriateness: prescription, acceptance by the patient, and continuous monitoring of adherence and risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular setting of care (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. Therefore, it is urgent assigning to each approach proposed in the literature the following characteristics: level of effectiveness, strength of evidence, setting of implementation, needed resources, and issues for its sustainability.

Introduction Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education.Methods and analysis This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision.Ethics and dissemination The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO‐ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.

Medical faculties have the responsibility to train tomorrow's doctors and in a crisis face the challenge of delivering students into the workforce promptly and safely. Worldwide, medical faculties have faced unprecedented disruptions from viral outbreaks and pandemics including SARS, Ebola, H1N1 and COVID-19 which bring unique challenges. Currently there is worldwide disruption to medical faculties and medical education due to COVID-19. Despite close links with clinical medicine and the known risks of pandemics, many medical faculties have been caught off guard without pandemic planning in place, to deal with an exponential rise in infections and deaths, overwhelmed health services and widespread community risk of transmission. Assessing transmission risk of COVID-19 in teaching, clinical and community attachments and continuing medical education is paramount as medical faculties face subsequent pandemics waves. Consensus statements based on best available evidence and international expertise from medical faculties in Asia, Australia and Europe were developed to help guide the protection of staff and students, priorities on teaching activities and further educational development. Infection prevention, infection control, contact tracing and medical surveillance are detailed to minimise transmission and to enhance safety. Recommendations on teaching activities planning can enhance responsiveness of medical faculties to tackle subsequent waves of COVID-19 infection. A global approach and dialogue are encouraged.

Background The relationship between COVID-19 and out-of-hospital cardiac arrests (OHCAs) has been shown during different phases of the first pandemic wave, but little is known about how to predict where cardiac arrests will increase in case of a third peak. Aim To seek for a correlation between the OHCAs and COVID-19 daily incidence both during the two pandemic waves at a provincial level. Methods We considered all the OHCAs occurred in the provinces of Pavia, Lodi, Cremona, Mantua and Varese, in Lombardy Region (Italy), from 21/02/2020 to 31/12/2020. We divided the study period into period 1, the first 157 days after the outbreak and including the first pandemic wave and period 2, the second 158 days including the second pandemic wave. We calculated the cumulative and daily incidence of OHCA and COVID-19 for the whole territory and for each province for both periods. Results A significant correlation between the daily incidence of COVID-19 and the daily incidence of OHCAs was observed both during the first and the second pandemic period in the whole territory (R = 0.4, pConclusions Our results suggest that strictly monitoring the pandemic trend may help in predict which territories will be more likely to experience an OHCAs’ increase. That may also serve as a guide to re-allocate properly health resources in case of further pandemic waves.

Considering the high and increasing prevalence of stress, approaches to mitigate stress-related biological processes become a matter of public health. Since supportive social interactions contribute substantially to mental and physical health, we set out to develop a social support stress management intervention and examined its effects on psychophysiological stress responses as well as self-reported stress in healthy women. In a parallel-group randomized controlled trial, registered in the DSRK (DRKS00017427), 53 healthy women were randomly assigned to a social support stress management or a waitlist control condition. All participants underwent a standardized psychosocial stress test where physiological and emotional stress responses were assessed by repeated measurements of cortisol, heart rate, heart rate variability and state anxiety. Also, all participants completed self-report questionnaires of perceived stress and social support at pre-intervention, post-intervention and follow-up four weeks later. Participants in the social support stress management showed a significantly attenuated integrated state anxiety response in comparison to those in the control condition, but conditions did not differ in any of the assessed physiological stress responses. The intervention significantly reduced perceived stress in comparison to the control condition, but perceived stress levels returned to baseline at follow-up. Our results indicated that the intervention had no effect on physiological responses to acute psychosocial stress, even though anxiety responses to stress were attenuated. However, the social support stress management intervention had a significant, albeit transient impact on perceived stress.

Drug-induced liver injury (DILI) with nintedanib has emerged as an adverse event of special interest in premarketing clinical trials. We characterized DILI with nintedanib in the real world and explored the underlying pharmacological basis. First, we assessed serious hepatic events reported to the Food and Drug Administration’s Adverse Event Reporting System by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment. Demographic and clinical features were inspected (seriousness, onset, discontinuation, dechallenge/rechallenge, concomitant drugs) to implement an ad hoc causality assessment scoring system. Second, we appraised physiochemical and pharmacokinetic parameters possibly predictive of DILI occurrence. Significant disproportionality was found for nintedanib as compared to pirfenidone (N = 91; ROR = 4.77; 95% CI = 3.15–7.39). Asian population, low body weight (59 kg), and rapid DILI onset (13.5 days) emerged as clinical features. Hospitalization and discontinuation were found in a significant proportion of cases (32% and 36%, respectively). In 24% of the cases, at least two potentially hepatotoxic drugs (statins, proton pump inhibitors, antibiotics) were recorded. Causality was at least possible in 92.3% of the cases. High lipophilicity and predicted in silico inhibition of liver transporters emerged as potential pharmacokinetic features supporting the biological plausibility. Although causality cannot be demonstrated, clinicians should consider early monitoring and medication review on a case-by-case basis.

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists’ parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8–10 mmHg, n = 84) or standard laparoscopic insufflation (10–12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

PurposeThis study aims to describe factors associated to treatment continuity and psychiatric relapses in patients treated with Long Acting Injectable antipsychotics (LAIs) in Bologna Community Mental Health Centers (CMHCs).MethodsNew LAI treatments administered between July 1, 2010 and June 30, 2015 in CMHCs were selected. The cohort was followed-up for 6 months; predictors of continuity and psychiatric admissions were investigated by using logistic regression- and Cox- analysis respectively.ResultsAmong the cohort of 1 070 patients, only 222 (21%) continued LAI treatment during the follow-up. LAI continuity was higher with first generation agents (OR: 1.71, 95%CI 1.18-2.49) and in case of previous psychiatric hospitalizations (OR 2.00, 95%CI 1.47-2.74). Incidence of psychiatric hospital admissions showed a sharp reduction in the follow-up compared with 6-month period before initiation (from 458 to 212), and was associated with previous psychiatric hospitalizations (HR 3.20, 95%CI 2.22-4.59), immigration (HR 3.13, 95%CI 1.28-7.69) and LAI discontinuation (HR 1.14, 95%Cl 1.01-1.97).ConclusionsPsychiatric hospital admission before LAI initiation was the main predictor both of LAI continuity and hospitalization during the follow-up.

Accurate lineage reconstruction of mammalian pre-implantation development is essential for inferring the earliest cell fate decisions. Lineage tracing using global fluorescence labeling techniques is complicated by increasing cell density and rapid embryo rotation, which hampers automatic alignment and accurate cell tracking of obtained four-dimensional imaging data sets. Here, we exploit the advantageous properties of primed convertible fluorescent proteins (pr-pcFPs) to simultaneously visualize the global green and the photoconverted red population in order to minimize tracking uncertainties over prolonged time windows. Confined primed conversion of H2B-pr-mEosFP-labeled nuclei combined with light-sheet imaging greatly facilitates segmentation, classification, and tracking of individual nuclei from the 4-cell stage up to the blastocyst. Using green and red labels as fiducial markers, we computationally correct for rotational and translational drift, reduce overall data size, and accomplish high-fidelity lineage tracing even for increased imaging time intervals – addressing major concerns in the field of volumetric embryo imaging.

Adjuvants have been used for decades to enhance the immune response to vaccines, in particular for the subunit-based adjuvants. Physicochemical properties of the adjuvant-protein antigen complexes, such as size, morphology, protein structure and binding, influence the overall efficacy and safety of the vaccine. Here we show how to perform an accurate physicochemical characterization of the nanoaluminum–ovalbumin complex. Using a combination of existing techniques, we developed a multi-staged characterization strategy based on measurements of increased complexity. This characterization cascade has the advantage of being very flexible and easily adaptable to any adjuvant-protein antigen combinations. It will contribute to control the quality of antigen–adjuvant complexes and immunological outcomes, ultimately leading to improved vaccines.

We present the case of a 75-year-old man with incidental finding of a left ventricular false chamber at echocardiography. A multimodality imaging approach including also transesophageal echocardiography and cardiac magnetic resonance imaging allowed to better characterize the lesion and identify it as a pseudoaneurysm. Surgery showed an infective aetiology, which is rare, due to the finding of a large abscess in the cavity.

Devices and sensors for identification of fallers can be used to implement actions to prevent falls and to allow the elderly to live an independent life while reducing the long-term care costs. In this study we aimed to investigate the accuracy of Timed Up and Go test, for fallers' identification, using fusion of features extracted from accelerometer data. Single and dual tasks TUG (manual and cognitive) were performed by a final sample (94% power) of 36 community dwelling healthy older persons (18 fallers paired with 18 non-fallers) while they wear a single triaxial accelerometer at waist with sampling rate of 200Hz. The segmentation of the TUG different trials and its comparative analysis allows to better discriminate fallers from non-fallers, while conventional functional tests fail to do so. In addition, we show that the fusion of features improve the discrimination power, achieving AUC of 0.84 (Sensitivity = Specificity = 0.83, 95% CI 0.62-0.91), and demonstrating the clinical relevance of the study. We concluded that features extracted from segmented TUG trials acquired with dual tasks has potential to improve performance when identifying fallers via accelerometer sensors, which can improve TUG accuracy for clinical and epidemiological applications.