A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.

Mental Health and Substance Use Among Patients in a North Carolina HIV Clinic.

BACKGROUND: The HIV/AIDS epidemic is a significant public health concern in North Carolina, and previous research has pointed to elevated mental health distress and substance use among HIV-infected populations, which may impact patients' adherence to medications. The aims of this study were to describe the prevalence of mental health and substance use issues among patients of a North Carolina HIV clinic, to examine differences by demographic characteristics, and to examine factors associated with suboptimal adherence to HIV medications. METHODS: This study was a secondary analysis of clinical data routinely collected through a health behavior questionnaire at a large HIV clinic in North Carolina. We analyzed data collected from February 2011 to August 2012. RESULTS: The sample included 1,398 patients. Overall, 12.2% of patients endorsed current symptomology indicative of moderate or severe levels of depression, and 38.6% reported receiving a psychiatric diagnosis at some point in their life. Additionally, 19.1% had indications of current problematic drinking, and 8.2% reported problematic drug use. Nearly one-quarter (22.1%) reported suboptimal adherence to HIV medications. Factors associated with poor adherence included racial/ethnic minority, age less than 35 years, and indications of moderate or severe depression. LIMITATIONS: The questionnaire was not completed systematically in the clinic, which may limit generalizability, and self-reported measures may have introduced social desirability bias. CONCLUSION: Patients were willing to disclose mental health distress, substance use, and suboptimal medication adherence to providers, which highlights the importance of routinely assessing these behaviors during clinic visits. Our findings suggest that treating depression may be an effective strategy to improve adherence to HIV medications.

Maintenance of a case-base for the retrieval of rotationally symmetric shapes for the design of metal castings

In this paper, we discuss the problem of maintenance of a CBR system for retrieval of rotationally symmetric shapes. The special feature of this system is that similarity is derived primarily from graph matching algorithms. The special problem of such a system is that it does not operate on search indices that may be derived from single cases and then used for visualisation and principle component analyses. Rather, the system is built on a similarity metric defined directly over pairs of cases. The problems of efficiency, consistency, redundancy, completeness and correctness are discussed for such a system. Performance measures for the CBR system are given, and the results for trials of the system are presented. The competence of the current case-base is discussed, with reference to a representation of cases as points in an n-dimensional feature space, and a Gramian visualisation. A refinement of the case base is performed as a result of the competence analysis and the performance of the case-base before and after refinement is compared.

Routine maintenance and sustainability of existing social housing

Improving the sustainability of the housing stock is a major challenge facing the UK social housing sector. UK social housing accounts for approximately 18% of total UK housing and generates maintenance costs in the region of 1.25 billion pounds per annum. The extent to which routine maintenance can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports the findings of a questionnaire survey examining current social housing maintenance practices and attitudes towards sustainability. The research found that, whilst the stock condition survey is the favoured format for determining maintenance need and economics the basis for priority setting; neither systematically addresses wider sustainability issues; and, whilst cost is a major barrier to more sustainable solutions being adopted, landlords are able and have the desire to improve their practices.

Routine maintenance and sustainability of existing social housing

Presently the UK social housing stock accounts for approximately 18% of the total UK housing with maintenance costs in the region of £1.25 billion per annum. In terms of its impact on the environment, housing is generally responsible for approximately 27% of the UK’s CO2 emissions. The extent to which routine maintenance (planned preventative and responsive) can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports on the findings of a series of in-depth interviews with social housing providers examining current social housing maintenance practices and attitudes towards sustainability. This paper will report the initial findings of interviews and outline a new performance based multi-criteria maintenance model from which an AHP hierarchy will be presented, integrating the principles of sustainability into maintenance strategies