Management of Portal Hypertension in Children

Management of portal hypertension in children has evolved over the past several decades. Portal hypertension can result from intrahepatic or extrahepatic causes. Management should be tailored to the child based on the etiology of the portal hypertension and on the functionality of the liver. The most serious complication of portal hypertension is gastroesophageal variceal bleeding, which has a mortality of up to 30%. Initial treatment of bleeding focuses on stabilizing the patient. Further treatment measures may include endoscopic, medical, or surgical interventions as appropriate for the child, depending on the cause of the portal hypertension. β-Blockers have not been proven to effectively prevent primary or secondary variceal bleeding in children. Sclerotherapy and variceal band ligation can be used to stop active bleeding and can prevent bleeding from occurring. Transjugular intrahepatic portosystemic shunts and surgical shunts may be reserved for those who are not candidates for transplant or have refractory bleeding despite medical or endoscopic treatment

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P <.0005). In patients with follow-up of > 5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity

E2F-1 Directly Regulates Thrombospondin 1 Expression

Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located −144/−137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering −144/−137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression

Developmental disruption of perineuronal nets in the medial prefrontal cortex after maternal immune activation

© The Author(s) 2016. Maternal infection during pregnancy increases the risk of offspring developing schizophrenia later in life. Similarly, animal models of maternal immune activation (MIA) induce behavioural and anatomical disturbances consistent with a schizophrenia-like phenotype in offspring. Notably, cognitive impairments in tasks dependent on the prefrontal cortex (PFC) are observed in humans with schizophrenia and in offspring after MIA during pregnancy. Recent studies of post-mortem tissue from individuals with schizophrenia revealed deficits in extracellular matrix structures called perineuronal nets (PNNs), particularly in PFC. Given these findings, we examined PNNs over the course of development in a well-characterized rat model of MIA using polyinosinic-polycytidylic acid (polyI:C). We found selective reductions of PNNs in the PFC of polyI:C offspring which did not manifest until early adulthood. These deficits were not associated with changes in parvalbumin cell density, but a decrease in the percentage of parvalbumin cells surrounded by a PNN. Developmental expression of PNNs was also significantly altered in the amygdala of polyI:C offspring. Our results indicate MIA causes region specific developmental abnormalities in PNNs in the PFC of offspring. These findings confirm the polyI:C model replicates neuropathological alterations associated with schizophrenia and may identify novel mechanisms for cognitive and emotional dysfunction in the disorder

Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

BACKGROUND: Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG) activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP) triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. RESULTS: The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25-35 Hz) and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25-35 Hz) peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. CONCLUSION: The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients

Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures

Dry Needling for Spine Related Disorders: a Scoping Review

Introduction/Background: The depth and breadth of research on dry needling (DN) has not been evaluated specifically for symptomatic spine related disorders (SRD) from myofascial trigger points (TrP), disc, nerve and articular structures not due to serious pathologies. Current literature appears to support DN for treatment of TrP. Goals of this review include identifying research published on DN treatment for SRD, sites of treatment and outcomes studied. Methods: A scoping review was conducted following Levac et al.’s five part methodological framework to determine the current state of the literature regarding DN for patients with SRD. Results: Initial and secondary search strategies yielded 55 studies in the cervical (C) region (71.43%) and 22 in the thoracolumbar-pelvic (TLP) region (28.57%). Most were randomized controlled trials (60% in C, 45.45% in TLP) and clinical trials (18.18% in C, 22.78% in TLP). The most commonly treated condition was TrP for both the C and TLP regions. In the C region, DN was provided to 23 different muscles, with the trapezius as treatment site in 41.88% of studies. DN was applied to 31 different structures in the TLP region. In the C region, there was one treatment session in 23 studies (41.82%) and 2–6 treatments in 25 (45.45%%). For the TLP region, one DN treatment was provided in 8 of the 22 total studies (36.36%) and 2–6 in 9 (40.9%). The majority of experimental designs had DN as the sole intervention. For both C and TLP regions, visual analogue scale, pressure pain threshold and range of motion were the most common outcomes. Conclusion: For SRD, DN was primarily applied to myofascial structures for pain or TrP diagnoses. Many outcomes were improved regardless of diagnosis or treatment parameters. Most studies applied just one treatment which may not reflect common clinical practice. Further research is warranted to determine optimal treatment duration and frequency. Most studies looked at DN as the sole intervention. It is unclear whether DN alone or in addition to other treatment procedures would provide superior outcomes. Functional outcome tools best suited to tracking the outcomes of DN for SRD should be explored.https://doi.org/10.1186/s12998-020-00310-

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Neuron-glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Junior Leader Fellowship Program by “la Caixa” Banking Foundation (LCF/BQ/LI18/11630006