Bariatric surgery: a practical pictorial guide for the diagnosis of common and rare complications with upper gastrointestinal imaging series

The aim of this educational poster is to illustrate the role of upper gastrointestinal series (UGS) in detecting the most common and some more rare complications in patients who underwent bariatric surgery procedures as \u2022 laparoscopic adjustable gastric band (LAGB) placement, \u2022 laparoscopic sleeve gastrectomy (LSG), \u2022 Roux-en-Y gastric bypass (RYGB). Our centre (Radiology Unit - Department of Medicine - University Hospital of Padova, Italy) excels in the follow-up of patients who underwent bariatic surgery interventions (in the Week Surgery Unit of the same Hospital). For this reason, our database is rich in images of early and late complications, directly from our clinical practice. In this poster we are going to present, describe and comment the findings to the benefit of all radiologists, not just for those whose field of study is the gastro-intestinal radiology, adding some useful tips for conducting a good examination with high diagnostic relevance

Loss of CDKL5 Causes Synaptic GABAergic Defects That Can Be Restored with the Neuroactive Steroid Pregnenolone-Methyl-Ether

: CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder characterised by early-onset drug-resistant epilepsy and impaired cognitive and motor skills. CDD is caused by mutations in cyclin-dependent kinase-like 5 (CDKL5), which plays a well-known role in regulating excitatory neurotransmission, while its effect on neuronal inhibition has been poorly investigated. We explored the potential role of CDKL5 in the inhibitory compartment in Cdkl5-KO male mice and primary hippocampal neurons and found that CDKL5 interacts with gephyrin and collybistin, two crucial organisers of the inhibitory postsynaptic sites. Through molecular and electrophysiological approaches, we demonstrated that CDKL5 loss causes a reduced number of gephyrin puncta and surface exposed γ2 subunit-containing GABAA receptors, impacting the frequency of miniature inhibitory postsynaptic currents, which we ascribe to a postsynaptic function of CDKL5. In line with previous data showing that CDKL5 loss impacts microtubule (MT) dynamics, we showed that treatment with pregnenolone-methyl-ether (PME), which promotes MT dynamics, rescues the above defects. The impact of CDKL5 deficiency on inhibitory neurotransmission might explain the presence of drug-resistant epilepsy and cognitive defects in CDD patients. Moreover, our results may pave the way for drug-based therapies that could bypass the need for CDKL5 and provide effective therapeutic strategies for CDD patients

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

Background. ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid oversedation, and would be as adequate as intravenous for awake patients, with fewer side effects and lower costs. This study compares two sedation strategies, in order to early reach and maintain the light sedation target. Methods. Multicenter, single-blind randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration >72 hours at ICU admission and predicted mortality >12% (Simplified Acute Physiology Score II >32 points) during the first 24 ICU hours. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. Primary outcome: percentage of work shifts with an observed Richmond Agitation-Sedation Scale (RASS) = target RASS \ub1 1. Secondary outcomes: protocol feasibility, delirium- and coma-free days, costs of drugs, length of ICU and hospital stay, ICU, hospital, and one-year mortality. Results. 348 patients were enrolled. There were no differences in the primary outcome: enteral 89.8 [74.1-100], intravenous 94.4 [78-100]%, p=0.20. Enteral-treated patients had more protocol violations: 81 (46.6%) vs 7 (4.2%), p<0.01, more self-extubations: 4 (2.4%) vs 14 (8.1%), p=0.03, a lighter sedative target (RASS = 0): 93 [71-100] vs 83 [61-100]%, p<0.01, and lower total costs for drugs: 2.39 [0.75- 9.78] vs 4.15 [1.20 -20.19] \u20ac/day with mechanical ventilation (p=0.01). Conclusions. Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration. ClinicalTrials.gov, Clinical Trial #NCT01360346, registered 25 March 2011, https://clinicaltrials.gov/ct2/show/NCT01360346. Registered on 25 March 2011

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

Abstract: Between 6–20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na+, K+, and Cl− through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Distinct metabolic states sustain the emergence of cell lineages in intestinal organoid regeneration

From the smallest cell to the whole body, thousands of gears work in concert in space and time to ensure the utmost expression of human physiology. How in the absence of a hierarchical control, single cells coordinate and give rise to complex tissues is a mystery of multicellular organisms. Borrowing from the science of complex systems, it has been hypothesized that a set of local rules govern the life of a single cell and that emergent properties stem from complex interactions at the population level. Here we study single-cell decision-making in the context of a complex self-organising eukaryotic tissue. With one of the highest turnover rates in the body, intestinal epithelium is a flourishing and dynamical territory where regenerative cell-types constantly sense the environment and need to decide which fate to acquire and which mature cell-type to become. To quantitatively track the single cells whilst keeping a holistic view of the emergent patterns at the population levels, we made use of organoid techniques which allow the in-vitro three-dimensional reproduction of the microanatomy and functions observed in-vivo. We studied the process of intestinal organoid regeneration, whereby a single cell rapidly grows into a symmetrical sphere of cells which ultimately buds into an asymmetrical mature organoid, with its crypts and villi that morphologically and functionally recapitulate the intestinal epithelium. Through the transcriptomic analysis at the single cell resolution, we characterized the metabolic fingerprints that support intestinal organoid regeneration and cell lineage acquisition. We further confirmed our results through high-throughput imaging in fixed and living single cells from mature intestinal organoids. Through manipulation experiments targeting newly found metabolic markers we generated organoids with different proportions of mature cell-types. Altogether, our findings suggest an instructive role for metabolism in cell decision-making, suggesting cell metabolic state as a putative candidate for understanding the coordination and collective behaviour at the system level

The Impact of End-User Aggregation on the Electricity Business Ecosystem: Evidence from Europe

This chapter explores the new local opportunities that have emerged in the energy sector thanks to the respective diffusion of new technologies together with a process of digitalization in communication, monitoring, and management services. Adopting the business ecosystem (BE) approach (Chesbrough, 2003; Gawer &amp; Cusumano, 2002; Iansiti &amp; Levien, 2004; Lewin &amp; Regine, 1999; Moore, 1993, 1996, 1998) we investigate the role that new business realities, the energy aggregators, which serve as intermediaries for an active participation of end-users, have in the electricity BE. In particular the chapter answers the following research questions: what are the main changes in the electricity BE due to the energy transition? What is the role of the energy aggregators within the electricity BE? What are the main barriers that can hinder changes? We answer these research questions adopting a multiple case study approach (Yin, 2003). For each case study we collected several information by secondary data. We organized the collected data using the 6C framework (context, cooperation, construct, configuration, capability, and change) proposed by Rong, Hu, Lin, Shi, and Guo (2015)