Neural stem cells (NSCs) possess great potential for neural tissue repair after traumatic injuries to the central nervous system (CNS). However, poor survival and self-renewal of NSCs after injury severely limits its therapeutic potential. Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS proteoglycans (CSPGs) in the brain extracellular matrix (ECM) have the ability to bind and potentiate trophic factor efficacy, and promote NSC self-renewal in vivo. In this study, we investigated the potential of CS-GAG hydrogels composed of monosulfated CS-4 (CS-A), CS-6 (CS-C), and disulfated CS-4,6 (CS-E) CS-GAGs as NSC carriers, and their ability to create endogenous niches by enriching specific trophic factors to support NSC self-renewal. We demonstrate that CS-GAG hydrogel scaffolds showed minimal swelling and degradation over a period of 15 days in vitro, absorbing only 6.5 ± 0.019% of their initial weight, and showing no significant loss of mass during this period. Trophic factors FGF-2, BDNF, and IL10 bound with high affinity to CS-GAGs, and were significantly (p < 0.05) enriched in CS-GAG hydrogels when compared to unsulfated hyaluronic acid (HA) hydrogels. Dissociated rat subventricular zone (SVZ) NSCs when encapsulated in CS-GAG hydrogels demonstrated ∼88.5 ± 6.1% cell viability in vitro. Finally, rat neurospheres in CS-GAG hydrogels conditioned with the mitogen FGF-2 demonstrated significantly (p < 0.05) higher self-renewal when compared to neurospheres cultured in unconditioned hydrogels. Taken together, these findings demonstrate the ability of CS-GAG based hydrogels to regulate NSC self-renewal, and facilitate growth factor enrichment locally.

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Background Appropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect. In fact, an anti-inflammatory, “M2-like” macrophage phenotype after TBI has been associated with neurogenesis, axonal regeneration, and improved white matter integrity (WMI). There already exist clinical trials seeking an M2-like bias through mesenchymal stem/stromal cells (MSCs). However, MSCs do not endogenously synthesize key signals that induce robust M2-like phenotypes such as interleukin-4 (IL-4). Methods To enrich M2-like macrophages in a clinically relevant manner, we augmented MSCs with synthetic IL-4 mRNA to transiently express IL-4. These IL-4 expressing MSCs (IL-4 MSCs) were characterized for expression and functionality and then delivered in a modified mouse TBI model of closed head injury. Groups were assessed for functional deficits and MR imaging. Brain tissue was analyzed through flow cytometry, multi-plex ELISA, qPCR, histology, and RNA sequencing. Results We observed that IL-4 MSCs indeed induce a robust M2-like macrophage phenotype and promote anti-inflammatory gene expression after TBI. However, here we demonstrate that acute enrichment of M2-like macrophages did not translate to improved functional or histological outcomes, or improvements in WMI on MR imaging. To further understand whether dysfunctional pathways underlie the lack of therapeutic effect, we report transcriptomic analysis of injured and treated brains. Through this, we discovered that inflammation persists despite acute enrichment of M2-like macrophages in the brain. Conclusion The results demonstrate that MSCs can be engineered to induce a stronger M2-like macrophage response in vivo. However, they also suggest that acute enrichment of only M2-like macrophages after diffuse TBI cannot orchestrate neurogenesis, axonal regeneration, or improve WMI. Here, we also discuss our modified TBI model and methods to assess severity, behavioral studies, and propose that IL-4 expressing MSCs may also have relevance in other cavitary diseases or in improving biomaterial integration into tissues.

IntroductionThe apparent diffusion coefficient (ADC) sequence is based on the diffusion properties of water molecules within tissues and correlates with tissue cellularity. ADC may have a role in predicting tumor grade for gliomas, and may in turn assist in identifying tumor biopsy sites. The purpose of this investigation was to assess the competence of preoperative ADC values in predicting tumor grades.MethodsThis was a retrospective investigation. We calculated the ADC values in the areas of greatest restriction in solid tumor components, and we recorded the pattern of contrast enhancement. Pathology reports masked to the imaging results were reviewed independently. We calculated the differences in the mean values of different tumor grades and high-grade and low-grade gliomas. A receiver operator curve (ROC) analysis assessed the predictive potential of ADC values for low-grade gliomas.ResultsForty-eight cases of glioma were included in our study. We noted a statistically significant difference in the lowest mean ADC values for the tumor regions of Grade IV lesions (333.83 ± 295.47) compared with Grade I lesions (653.20 ± 145.07). On ROC analysis, we noted an area under the curve (AUC) of 0.80 for the lowest ADC value in the whole tumor region, which was a predictor of low-grade glioma with 95 % confidence interval (CI) of 0.675-0.926. The sensitivity of the lowest ADC value was 84.5% for high-grade lesions.ConclusionGiven our findings that the means of the lowest ADC value are significantly different between low and high-grade gliomas with an AUC of 0.80 for ADC as a predictor of low-grade lesions and a sensitivity of 84.5% for high-grade lesions, ADC values contain some predictive properties of tumor grading. ADC values may be a valuable parameter in the assessment and treatment of tumors.

RCTS is an independent predictor of unfavourable outcomes and mortality among patients undergoing emergency DC.

Background: Depression is a great cause of morbidity around the world. Not one person seems to escape the hollow dread that the disease can bring forth. Aims: Although living in a large extended family which serves as a social support is common in Pakistan, why we still suffer from anxiety and depression just as often if not more than those in other countries? Method: We checked studies conducted in different localities of Pakistan over the past 10 years to find prevalence values of anxiety and depression. Results: The values of anxiety and depression ranging from 22% to as high as 60% in a given population high rates necessitate the spread of awareness and action against mental health issues. Conclusions: It is a mental disorder that can create numerous concerns in many aspects of the sufferer's life. The disabling moods of depression can damage a person's marriage, family relationships, friendships, job performance, and health. The longer depression persists, the more widespread the damage. Major depression can result in people shutting themselves off from the support of friends and family or striking out violently by verbally and physically attacking others.

SUMMARYWe present a case of congenital malignant melanoma of the scalp in a neonate. The child was born through caesarean section with a swelling, the size of a tennis ball, on the posterior scalp. At presentation to the clinic at 25 days after birth, the swelling had significantly increased in size and ulcerated. An excision was carried out but, because of extensive haemorrhage and haemodynamic instability, the procedure was limited to subtotal resection. Later on, completion of the excision and flap coverage of the wound were performed. After an initial stable course of a few months, the child came back with local recurrence. A re-excision was planned but the child developed pneumonia resulting in sepsis leading to the demise of the child. The report adds to the literature by describing a rare entity and challenges of managing large vascular scalp lesions with complete excision and defect coverage. BACKGROUND