Total orthotopic small bowel transplantation in swine under FK 506

Previous experimental studies in rodents and in dogs have established the efficacy of FK 506 in controlling the immunologic events following small bowel or multivisceral transplantation.1–5 To complete the assessment of FK 506 in experimental small bowel transplantation, we present here our experience with the frequently used swine model

Top-down control of visual sensory processing during an ocular motor response inhibition task

The study addressed whether top-down control of visual cortex supports volitional behavioral control in a novel antisaccade task. The hypothesis was that anticipatory modulations of visual cortex activity would differentiate trials on which subjects knew an anti- versus a pro-saccade response was required. Trials consisted of flickering checkerboards in both peripheral visual fields, followed by brightening of one checkerboard (target) while both kept flickering. Neural activation related to checkerboards before target onset (bias signal) was assessed using electroencephalography. Pretarget visual cortex responses to checkerboards were strongly modulated by task demands (significantly lower on antisaccade trials), an effect that may reduce the predisposition to saccade generation instigated by visual capture. The results illustrate how top-down sensory regulation can complement motor preparation to facilitate adaptive voluntary behavioral control

Quantum diffusion with disorder, noise and interaction

Disorder, noise and interaction play a crucial role in the transport properties of real systems, but they are typically hard to control and study both theoretically and experimentally, especially in the quantum case. Here we explore a paradigmatic problem, the diffusion of a wavepacket, by employing ultra-cold atoms in a disordered lattice with controlled noise and tunable interaction. The presence of disorder leads to Anderson localization, while both interaction and noise tend to suppress localization and restore transport, although with completely different mechanisms. When only noise or interaction are present we observe a diffusion dynamics that can be explained by existing microscopic models. When noise and interaction are combined, we observe instead a complex anomalous diffusion. By combining experimental measurements with numerical simulations, we show that such anomalous behavior can be modeled with a generalized diffusion equation, in which the noise- and interaction-induced diffusions enter in an additive manner. Our study reveals also a more complex interplay between the two diffusion mechanisms in regimes of strong interaction or narrowband noise.Comment: 11 pages, 10 figure

Bioethical and medico-legal implications of withdrawing artificial nutrition and hydration from adults in critical care

The withdrawal of artificial nutrition and hydration or other life-sustaining treatments is a clinical decision, made in ICUs or in other settings, involving patients suffering from serious and irreversible diseases or impaired consciousness. Such clinical decisions must be made in the best interests of the patient, and must respect the wishes previously expressed by patients, laid down in their wills, in advance directives or in information passed on by relatives or legally appointed health-care agents, and in observance of common bioethical and legal rules in individual nations. Intensivists who are expert in the management of lifesustaining treatments are also involved in deciding when to withdraw futile therapies and instigate end-of-life care procedures for dying patients, with the sole aim of providing comfort and ensuring that suffering is not prolonged unnecessaril

Identification of Protein Tyrosine Phosphatase Receptor Gamma Extracellular Domain (sPTPRG) as a Natural Soluble Protein in Plasma

BACKGROUND:PTPRG is a widely expressed protein tyrosine phosphatase present in various isoforms. Peptides from its extracellular domain have been detected in plasma by proteomic techniques. We aim at characterizing the plasmatic PTPRG (sPTPRG) form and to identify its source.METHODOLOGY/PRINCIPAL FINDINGS:The expression of sPTPRG was evaluated in human plasma and murine plasma and tissues by immunoprecipitation and Western blotting. The polypeptides identified have an apparent Mr of about 120 kDa (major band) and 90 kDa (minor band) respectively. Full length PTPRG was identified in the 100.000 7g pelleted plasma fraction, suggesting that it was present associated to cell-derived vesicles (exosomes). The release of sPTPRG by HepG2 human hepatocellular carcinoma cell line was induced by ethanol and sensitive to metalloproteinase and not to Furin inhibitors. Finally, increased levels of the plasmatic 3c120 kDa isoform were associated with the occurrence of liver damage.CONCLUSIONS:These results demonstrate that sPTPRG represent a novel candidate protein biomarker in plasma whose increased expression is associated to hepatocyte damage. This observation could open a new avenue of investigation in this challenging field

In‐Depth Immunological Typization of Children with Sickle Cell Disease: A Preliminary Insight into Its Plausible Correlation with Clinical Course and Hydroxyurea Therapy

Sickle cell disease (SCD) is a condition of functional hypo‐/a‐splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune‐dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in‐depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case–control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi‐squared tests, t‐tests, and Pearson’s correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T‐cell depletion with prevalence of memory T‐cell compartment, NK and B‐naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched‐memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p‐value of <0.05). The mean CD4+ central‐memory T‐cell% count was the single independent variable showing a positive correlation with vaso‐occlusive crisis score in the SCD group (Pearson’s R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU‐related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo‐/a‐splenism immuno‐chemoprophylactic recommendations

Distribution of different isoforms of receptor protein tyrosine phosphatase \u3b3 (Ptprg-RPTP \u3b3) in adult mouse brain: upregulation during neuroinflammation.

The receptor protein tyrosine phosphatase \u3b3 (Ptprg-RPTP\u3b3) is a receptor protein widely expressed in many tissues, including the central nervous system (CNS). Several RPTP\u3b3 isoforms are expressed in the brain during development and in adulthood, but their distribution and role are unknown. In this study, we investigated the distribution of some RPTP\u3b3 isoforms in the adult brain using antibodies against the epitopes localized in the C- and in the N-terminal domains of the full length isoform of RPTP\u3b3. We found a predominant and widespread neuronal positivity throughout the neocortex, hippocampus, striatum and in many nuclei of the brainstem and cerebellum. At least 2 distinct isoforms that can co-exist in various compartments in the same cell are detectable in different neuron types. Immunopositivity for epitopes located in both the N- and C-terminus domains were found in the neuropil of cortical and hippocampal neurons, whereas the N-terminal domain positivity was found in the soma, often without colocalization with its C-terminal counterpart. Among glial cells, some protoplasmic and perivascular astrocytes and the cerebellar Bergmann glia, express RPTP\u3b3. The astrocytic expression of RPTP\u3b3 and putative processing isoforms of 120 and 80 kDa increases during neuroinflammation, in particular 24 h after LPS treatment. Activated astrocytes were found to be strongly positive for RPTP\u3b3 also in a mice model of Alzheimer's disease. Our results confirm previous findings and enrich the current knowledge of RPTP\u3b3 distribution in the CNS, highlighting a role of RPTP\u3b3 during neuroinflammation processes

Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use

Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. Implications: In the light of the current imbalance between gammaglobulins’ demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes