Similar Alterations of the Stratum Corneum Ceramide Profile in Atopic Dermatitis, Psoriasis, and Ichthyosis::Results from a Systematic Review and Meta-Analysis

Drug Delivery Technolog

Relational trauma and its impact on late-adopted children

This paper describes work with two children, placed for late adoption who have suffered relational trauma. The paper explores the long-term consequences of such trauma, which includes problems with affect regulation, difficulties in generalising from one experience to another and shifts between phantasies of omnipotent control and sudden helplessness. Using drawings from one boy's therapy, it is argued that many children adopted at a later age live in two worlds, both internal and external, and internal objects and memories from the past vie with new experiences and representations for ascendancy within the child's mind. Which is more real: the world of the past or the present? The paper describes how these children experienced sudden and troubling shifts in focus as they were catapulted from feeling states belonging to one world to the other. The paper ends with a consideration of how findings from neuroscience may help us to understand these sudden shifts and overall argues for a pulling together of psychoanalytic thinking and child development research findings to support the child in psychotherapy

Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis:results of a randomized controlled trial

The epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab. We conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1–100 mg guselkumab or placebo for 16 weeks and barrier dynamics monitored throughout. Barrier function was measured by trans-epidermal water loss measurements. Untargeted ceramide profiling was performed using liquid chromatography-mass spectrometry after SC was harvested using tape-stripping. The barrier function and ceramide profile of lesional skin normalized to that of controls during treatment with guselkumab, but not placebo. This resulted in significant differences compared to placebo at the end of the treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Nonlesional skin remained similar throughout treatment. Guselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile, and disease severity demonstrate their interdependency.</p

Oral prednisolone suppresses skin inflammation in a healthy volunteer imiquimod challenge model

Imiquimod (IMQ) is a topical agent that induces local inflammation via the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in healthy volunteers for proof-of-pharmacology trials. The aim of this study was to profile the cellular, biochemical, and clinical effects of the marketed anti-inflammatory compound prednisolone in an IMQ model. This randomized, double-blind, placebo-controlled study was conducted in 24 healthy volunteers. Oral prednisolone (0.25 mg/kg/dose) or placebo (1:1) was administered twice daily for 6 consecutive days. Two days after treatment initiation with prednisolone or placebo, 5 mg imiquimod (IMQ) once daily for two following days was applied under occlusion on the tape-stripped skin of the back for 48 h in healthy volunteers. Non-invasive (imaging and biophysical) and invasive (skin punch biopsies and blister induction) assessments were performed, as well as IMQ ex vivo stimulation of whole blood. Prednisolone reduced blood perfusion and skin erythema following 48 h of IMQ application (95% CI [−26.4%, −4.3%], p = 0.0111 and 95% CI [−7.96, −2.13], p = 0.0016). Oral prednisolone suppressed the IMQ-elevated total cell count (95% CI [−79.7%, −16.3%], p = 0.0165), NK and dendritic cells (95% CI [−68.7%, −5.2%], p = 0.0333, 95% CI [−76.9%, −13.9%], p = 0.0184), and classical monocytes (95% CI [−76.7%, −26.6%], p = 0.0043) in blister fluid. Notably, TNF, IL-6, IL-8, and Mx-A responses in blister exudate were also reduced by prednisolone compared to placebo. Oral prednisolone suppresses IMQ-induced skin inflammation, which underlines the value of this cutaneous challenge model in clinical pharmacology studies of novel anti-inflammatory compounds. In these studies, prednisolone can be used as a benchmark.</p

Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): Study protocol for a multicentre randomized controlled trial

Background: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improve

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial

BACKGROUND: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. METHODS: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide da

The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial

Background: The necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer.Method: This was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary che-moradiotherapy in patients with occult metastatic disease.Results: Of the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (4 4.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p 1/4 0.040).Conclusions: Staging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection.(c) 2022 Published by Elsevier Ltd.Surgical oncolog

Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}=2.76 TeV

The elliptic, $v_2$, triangular, $v_3$, and quadrangular, $v_4$, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions and (anti-)protons in Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range $|\eta|<0.8$ at different collision centralities and as a function of transverse momentum, $p_{\rm T}$, out to $p_{\rm T}=20$ GeV/$c$. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for $p_{\rm T}>8$ GeV/$c$. The small $p_{\rm T}$ dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to $p_{\rm T}=8$ GeV/$c$. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least $p_{\rm T}=8$ GeV/$c$ indicating that the particle type dependence persists out to high $p_{\rm T}$.Comment: 16 pages, 5 captioned figures, authors from page 11, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186