Effect of new curcumin‐containing nanostructured lipid dispersions on human keratinocytes proliferative responses

This study describes the production and characterization of nanostructured lipid dispersions (NLDs) containing curcumin (CUR) as new tools for curcumin topical delivery. Four types of NLDs based on monoolein in association with different emulsifiers were produced: Na cholate and poloxamer 407 (NLD1), poloxamer alone (NLD2), the mixture of Na cholate and Na caseinate (NLD3) and Na cholate alone (NLD4). Morphology and dimensional distribution of lipid dispersions were investigated by cryo‐TEM and photon correlation spectroscopy (PCS). In vitro studies based on Franz cell, membrane nylon and stratum corneum–epidermis (SCE) were carried out to compare the four NLDs in terms of cytotoxicity in human keratinocytes and CUR diffusion. Our PCS studies showed differences in particles diameter among the different NLDs. In addition, cytotoxicity results in HaCaT cells evidenced that NLD1 and NLD2 were toxic at doses over 1 μm . Therefore, cryo‐TEM was determined only for NLD3 and NLD4 showing that CUR did not affect their structure. Diffusion measurement in SCE and nylon membrane evidenced that CUR had a time‐delayed release for NLD4. The ‘wound healing’ effect of NLD3 and NLD4 with and without CUR analysed keratinocytes in vitro, and a clear inhibition of cell proliferation/migration by CUR was observed. This effect was mediated by the inhibition of cyclin D1 expression as a consequence of the impaired NFkB activation. This study confirms the antiproliferative properties of CUR and evidenced a new possible model of CUR topical delivery for hyperproliferative cutaneous diseases such as psoriasis.     

Muscle strengthening intervention for boys with haemophilia: Developing and evaluating a best‐practice exercise programme with boys,families and health‐care professionals

BackgroundMuscle strengthening exercises have the potential to improve outcomes for boys with haemophilia, but it is unclear what types of exercise might be of benefit. We elicited the views of health‐care professionals, boys and their families to create and assess a home‐based muscle strengthening programme.ObjectiveTo design and develop a muscle strengthening programme with health‐care professionals aimed at improving musculoskeletal health, and refine the intervention by engaging boys with haemophilia and their families (Study 1). Following delivery, qualitatively evaluate the feasibility and acceptability of the exercise programme with the boys and the study''s physiotherapists (Study 2).DesignA person‐based approach was used for planning and designing the exercise programme, and evaluating it post‐delivery. The following methods were utilized: modified nominal group technique (NGT) with health‐care professionals; focus group with families; exit interviews with boys; and interviews with the study''s physiotherapists.ResultsThemes identified to design and develop the intervention included exercises to lower limb and foot, dosage, age accommodating, location, supervision and monitoring and incentivization. Programme refinements were carried out following engagement with the boys and families who commented on: dosage, location, supervision and incentivization. Following delivery, the boys and physiotherapists commented on progression and adaptation, physiotherapist contact, goal‐setting, creating routines and identifying suitable timeframes, and a repeated theme of incentivization.ConclusionsAn exercise intervention was designed and refined through engagement with boys and their families. Boys and physiotherapists involved in the intervention''s delivery were consulted who found the exercises to be generally acceptable with some minor refinements necessary.     

MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies

MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case-control study was to identify pathology-related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnosed pathology: (i) no shoulder pathology, (ii) chronic rotator cuff tendinopathy, and (iii) degenerative RCTs. In total, 14 patients were included. Venous blood samples (“liquid biopsies”) were collected from each patient and serum levels of 187 miRNAs were determined. Subsequently, the change in expression of nine candidate miRNAs was verified in tendon biopsy samples, collected from patients who underwent arthroscopic shoulder surgery between 2015 and 2018. Overall, we identified several miRNAs to be progressively deregulated in sera from patients with either chronic rotator cuff tendinopathy or degenerative RCTs. Importantly, for the several of these miRNAs candidates repression was also evident in tendon biopsies harvested from patients who were treated for a supraspinatus tendon tear. As similar expression profiles were determined for tendon samples, the newly identified systemic miRNA signature has potential as novel diagnostic or prognostic biomarkers for degenerative rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research^® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. Inc. J Orthop Res 38:202–211, 2020     

Evaluation der Behandlungsergebnisse einer psychiatrischen Aufnahmestation

BACKGROUND: Quality management is an important management tool in modern health care systems. This applies also to the mental health care system, where in the past decade many concepts have been developed on how to implement quality management appropriately and successfully. However, for the German speaking countries there are only very few studies on the evaluation of therapy outcome in psychiatric inpatient populations available, furthermore they deal primarily with diagnostic subgroups. The aim of this study was to develop a method to assess the quality of therapy on regular psychiatric admission wards. An important aspect was to include all diagnostic subgroups of a psychiatric inpatient population. METHODS: In an explorative field study and by means of a specially designed evaluation method, therapy courses of a psychiatric inpatient population were assessed. Indicators of therapy outcome were: psychopathology, level of psychosocial functioning, motivation of the patient for therapy, suicide attempts, legal status of the patient, patient violence and coercive treatment of the patient. The following assessment and rating scales were used: Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAMD), Global Assessment of Function (GAF), Social and Occupational Functioning Assessment Scale (SOFAS) and the Symptom-Checklist SCL-9. RESULTS: Changes in the courses of therapy of a psychiatric inpatient population in all diagnostic subgroups in the dimensions psychopathology and level of social functioning could be reproduced significantly using BPRS, HAMD and GAF scales. Difference values T(1)-T(2) were 6.6 +/- 6.9 (p = 0.019) in BPRS, 5.1 +/- 8.1 (p = 0.029) in HAMD and -5.5 +/- 10.1 (p = 0.028) in GAF. The entire battery of rating scales was successfully applied in 32% of all patients (drop out rate: 68%). In the subgroup of immigrant patients the entire battery of rating scales could be applied only in 17.4%, which accounts for a significantly higher drop out rate (82.6%; p = 0.067). DISCUSSION: Using the presented evaluation system therapy outcome and quality of therapy are easy to assess. The results of the quality assessment can be used in further therapeutic processes.     

Reprogramming of virus-specific T cells into leukemia-reactive T cells using T cell receptor gene transfer

T cells directed against minor histocompatibility antigens (mHags) might be responsible for eradication of hematological malignancies after allogeneic stem cell transplantation. We investigated whether transfer of T cell receptors (TCRs) directed against mHags, exclusively expressed on hematopoietic cells, could redirect virus-specific T cells toward antileukemic reactivity, without the loss of their original specificity. Generation of T cells with dual specificity may lead to survival of these TCR-transferred T cells for prolonged periods of time in vivo due to transactivation of the endogenous TCR of the tumor-reactive T cells by the latent presence of viral antigens. Furthermore, TCR transfer into restricted T cell populations, which are nonself reactive, will minimize the risk of autoimmunity. We demonstrate that cytomegalovirus (CMV)-specific T cells can be efficiently reprogrammed into leukemia-reactive T cells by transfer of TCRs directed against the mHag HA-2. HA-2-TCR-transferred CMV-specific T cells derived from human histocompatibility leukocyte antigen (HLA)-A2+ or HLA-A2- individuals exerted potent antileukemic as well as CMV reactivity, without signs of anti-HLA-A2 alloreactivity. The dual specificity of these mHag-specific, TCR-redirected virus-specific T cells opens new possibilities for the treatment of hematological malignancies of HLA-A2+ HA-2-expressing patients transplanted with HLA-A2-matched or -mismatched donors.