Shape-defined solid micro-objects from poly(d,l-lactic acid) as cell-supportive counterparts in bottom-up tissue engineering.

In bottom-up tissue engineering, small modular units of cells and biomaterials are assembled toward â€‹larger and more complex ones. In conjunction with a new implementation of this approach, a novel method to fabricate microscale objects from biopolymers by thermal imprinting on water-soluble sacrificial layers is presented. By this means, geometrically well-defined objects could be obtained without involving toxic agents in the form of photoinitiators. The micro-objects were used as cell-adhesive substrates and cell spacers in engineered tissues created by cell-guided assembly of the objects. Such constructs can be applied both for in vitro studies and clinical treatments. Clinically relevantly sized aggregates comprised of cells and micro-objects retained their viability up to 2 weeks of culture. The aggregation behavior of cells and objects showed to depend on the type and number of cells applied. To demonstrate the micro-objects' potential for engineering vascularized tissues, small aggregates of human bone marrow stromal cells (hMSCs) and micro-objects were coated with a layer of human umbilical vein endothelial cells (HUVECs) and fused into larger tissue constructs, resulting in HUVEC-rich regions at the aggregates' interfaces. This three-dimensional network-type spatial cellular organization could foster the establishment of (premature) vascular structures as a vital prerequisite of, for example, bottom-up-engineered bone-like tissue.

Neurodevelopmental liability to schizophrenia: the complex mediating role of age at onset and premorbid adjustment.

Large individual variation in the clinical presentation of schizophrenia-spectrum disorders raises key questions regarding their aetiological underpinnings. In this respect, age at onset of the disorder is a particularly interesting marker of liability, as it has been reported to be associated with other signs of developmental compromise, such as male gender, increased presence of familial history of psychosis and poor premorbid adjustment, as well as a more severe clinical outcome in terms of cognition and symptomatology. The association between these variables has encouraged a neurodevelopmental perspective of the aetiological mechanisms involved in the pathophysiology of schizophrenia. However, the complex relationships within neurobiological liability markers, and between these markers and clinical outcome, remain to be understood. In the present study, we used a path-analytic approach to explore: i) the fit of the model to observed data; and both ii) direct and iii) indirect associations between the variables. In a sample of 106 patients with schizophrenia-spectrum disorders, we found a good fit of the model to the observed data, providing further evidence that supports a neurodevelopmental pathway to the disease in a subgroup of patients. However, the most parsimonious model showed complex relationships, where age at onset and premorbid functioning acted as mediators between gender, familial history of psychosis and clinical outcome. These findings refine earlier explanations of the neurobiological basis of schizophrenia, with potential applications in genetic studies based on more homogeneous forms of the disease. We further discuss the putative implications of our results in clinical practice and prevention policies.

[Serotonin-noradrenalin reuptake inhibitors in the treatment of non-malignant pain syndromes; a systematic review]. / Serotonine-noradrenalineheropnameremmers bij chronische niet-maligne pijnsyndromen; een systematisch overzicht.

BACKGROUND: Chronic pain and depressive symptoms are often comorbid. Antidepressants seem to influence not only the symptoms of depression but also the perception of pain. AIM: To give a systematic overview of the efficacy and safety of serotonin-noradrenalin reuptake inhibitors (SNRI) in the treatment of chronic non-malignant pain syndromes. METHODS: We reviewed the literature by means of PubMed and PsycInfo using combinations of the words 'pain' 'venlafaxine' and 'duloxetine'. We selected clinical studies that investigated the influence of SNRIs on pain perception. RESULTS: Fourteen articles met our selection criteria. Medical conditions involved were fibromyalgia, diabetic neuropathy and post mastectomy pain. Twelve studies demonstrated the efficacy and safety of venlafaxine and duloxetine in the treatment of non-malignant pain. CONCLUSION: The results revealed that SNRIs are effective in reducing pain particularly in the treatment of diabetic neuropathy. Results with regard to the other medical conditions are less clear. More research is needed to find out in which medical conditions SNRIs have a significant pain reducing effect and why this effect does not hold in the case of other medical conditions.

Standard Pseudoisochromatic Plates part 2.

The Standard Pseudoisochromatic Plates part 2 are able to detect acquired blue-yellow color vision defects as well as acquired and congenital red-green color vision defects. One test plate might be age dependent. The value of 3 test plates is not clear.