The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

Psychomotor therapy targeting anger and aggressive behaviour in individuals with mild or borderline intellectual disabilities: A systematic review

Background: Poor anger regulation is considered a risk factor of aggression in individuals with mild or borderline intellectual disabilities. Psychomotor therapy (PMT) targets anger regulation through body- and movement-oriented interventions. This study aims to inform practitioners on efficacy and research-base of PMT in this population.

Method: This systematic review evaluated nine studies which met inclusion criteria in terms of participants, intervention procedures, outcomes and certainty of evidence.

Results: Seven studies revealed a substantial reduction of aggressive behaviour or anger. Certainty of evidence was rated inconclusive in most cases due to absence of experimental control.

Conclusions: We can conclude that body-oriented PMT, involving progressive relaxation and meditation procedure “Soles of the Feet”, is a promising approach. However, the paucity of studies and methodological limitations preclude classifying it as an evidence-based practice. This suggests stronger methodological research and research aimed at PMT’s mechanisms of action (e.g., improved interoceptive awareness) is warranted.     

Recurrent Ischemic Stroke – A Systematic Review and Meta-Analysis

ObjectivesRecurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time.Methods and materialsA systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019.ResultsThe search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence.ConclusionStroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.     

Population pharmacokinetic model for human growth hormone in adult patients in chronic dialysis compared with healthy subjects

ObjectiveTo develop a population pharmacokinetic (PK) model of recombinant human growth hormone (rhGH) treatment in patients with end-stage renal disease (ESRD) and healthy volunteers (HVs), to support future study design.DesignThis was an open, non-randomized, single-centre parallel-group study lasting 8–9 days. Various compartment models with first-order and Michaëlis-Menten absorption and elimination were explored. Eleven adult ESRD patients and 10 matched HVs received 50 μg/kg/day rhGH (subcutaneous (s.c.) injection) for 8 or 7 days, respectively. Blood samples were drawn every 30 min for 24 h following dosing on Days 0, 7 and 8 (ESRD patients). Influence of the covariates subject group (ESRD/HV), gender, weight, and dialysis flow-rate on model parameters was examined.ResultsThe final model was one-compartmental with Michaëlis-Menten absorption and elimination. The following estimates were obtained: maximum absorption rate (VMA) – 11.3 μg/kg/h (both groups); amount of drug corresponding to half-maximum absorption rate (KMA) – 1.06 and 18.8 μg/kg (ESRD patients and HVs, respectively; P < 0.001); maximum elimination rate (VM) – 9.37 and 13.0 μg/kg/h (ESRD patients and HVs, respectively; P < 0.001); amount of drug corresponding to half-maximum elimination rate – 18.9 μg/kg (both groups). Significant differences in KMA and VM between HVs and ESRD patients corresponded to higher absorption and lower elimination rates in ESRD, but all GH profiles were back to baseline by 20–22 h and no overall accumulation occurred. Simplified posterior predictive checks indicated that the model satisfactorily captured PK. All non-compartmental estimates for AUC_0–24h and C_max lay within 95% confidence limits of the simulated distributions.ConclusionsA population PK model was established, which showed acceptable performance for trial-simulation purposes.     

A Haemolytic Transfusion Reaction without Demonstrable Antibodies in Vitro

A severe haemolytic reaction after transfusion of apparently compatible blood was observed, without isoantibodies being detectable in the patient's serum.
From survival studies with Wr tagged red cells could be concluded that the abnormal destruction of the transfused red cells is of immunological origin.

Résumé

Une réaction hémolytique grave après transfusion de sang apparemment compatible a été observée, sans que l'on puisse mettre en évidence des iso-anticorps dans le sérum du patient.
Des étudev pratiquées avec des érythrocytes marqués au ⁵¹Cr, on peut conclure que la destruction anormale des érythrocytes transfusés a une origine immunologique.

Zusammenfassung

EB wird eine schwere hämolytische Transfusionsreaktion beschrieben, bei welcher im Empfängerserum Isoantikörper nicht nachgewiesen werden konnten. Auf Grund von Überlebenszeitbestimmungen mit ⁵¹Cr markierten Zellen wurde gescblossen, daß der rasche Abbau der Spendersellen trotzdem auf eincm Immunmechanismus beruht.     

Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis

Vitamin D has been associated with a decreased risk of multiple sclerosis (MS). In this study, serum 1, 25-dihydroxyvitamin D (1, 25-(OH)2 vitD) and 25-hydroxyvitamin D (25-OH vitD), regulatory T cell percentages and naïve and memory T helper cell subsets were measured in 26 patients with multiple sclerosis, 21 who were not on treatment with disease modifying therapy. These studies showed an inverse correlation between 25-OH vitD levels and Treg cell percentages and a direct correlation between Treg cell percentages and 1, 25-(OH)2 vitD:25-OH vitD ratios. In addition, 25-OH vitD levels correlated directly and 1, 25-(OH)2 vitD:25-OH vitD ratios correlated inversely with CXCR3+ naïve T helper cell percentages and CXCR3+naïve:CXCR3+ memory T helper cell ratios. All together, these data demonstrate that vitamin D measurements can reflect measures of immune status among patients with MS.     

Validation of an Arabic multi-informant psychiatric diagnostic interview for children and adolescents: Development and Well Being Assessment-Arabic (DAWBA-Arabic)

Background

Countries in the Arab region lack a valid Arabic psychiatric diagnostic interview for children and adolescents. We set out to establish the diagnostic validity of the Arabic version of the Development and Well Being Assessment (DAWBA-Arabic), a multi-informant structured interview for predicting DSM-IV-TR diagnoses.

Methods

The DAWBA was translated, updated, and administered to 45 participants (child and adolescent psychiatric outpatients and their parents) as part of a clinic registry. Two clinicians, blinded to their respective diagnoses, formulated the DAWBA diagnoses. Participants also underwent a clinical evaluation by a child and adolescent psychiatrist who generated clinical diagnoses according to the DSM-IV-TR.

Results

Inter-rater reliabilities were .93, .82, and .72 for disruptive disorders, mood disorders and anxiety disorders respectively. Agreement between DAWBA and clinical diagnoses was substantial for disruptive disorders (κ = .0.82) and mood disorders (κ = 0.74), and moderate for anxiety disorders (κ = 0.46).

Conclusion

The DAWBA-Arabic could serve as a valid and reliable clinical tool for assessing psychiatric disorders among children and adolescents in the Arab region.     

Towards quantifying the aesthetic outcomes of breast cancer treatment: comparison of clinical photography and colorimetry

Rationale, aims and objectives Scarring is a significant cause of dissatisfaction for women who undergo breast surgery. Scar tissue may be clinically distinguished from normal skin by aberrant colour, rough surface texture, increased thickness (hypertrophy) and firmness. Colorimeters or spectrophotometers can be used to quantitatively assess scar colour, but they require direct patient interaction and can cost thousands of dollars. By comparison, digital photography is already in widespread use to document clinical outcomes and requires less patient interaction. Thus, assessment of scar coloration by digital photography is an attractive alternative. The goal of this study was to compare colour measurements obtained by digital photography and colorimetry. Methods Agreements between photographic and colorimetric measurements of colour were evaluated. Experimental conditions were controlled by performing measurements on artificial scars created by a make‐up artist. The colorimetric measurements of the artificial scars were compared with those reported in the literature for real scars in order to confirm the validity of this approach. We assessed the agreement between the colorimetric and photographic measurements of colour using a hypothesis test for equivalence, the intraclass correlation coefficient and the Bland–Altman method. Results Overall, good agreement was obtained for three parameters (L*a*b*) measured by colorimetry and photography from the results of three statistical analyses. Conclusion Colour measurements obtained by digital photography were equivalent to those obtained using colorimetry. Thus, digital photography is a reliable, cost‐effective measurement method of skin colour and should be further investigated for quantitative analysis of surgical outcomes.