Screening for Diabetes and Hypertension in a Rural Low Income Setting in Western Kenya Utilizing Home-Based and Community-Based Strategies

BACKGROUND: The burdens of hypertension and diabetes are increasing in low- and middle-income countries (LMICs). It is important to identify patients with these conditions early in the disease process. The goal of this study, therefore, is to compare community- versus home-based screening for hypertension and diabetes in Kenya. METHODS: This was a feasibility study conducted by the Academic Model Providing Access to Healthcare (AMPATH) program in Webuye, a town in western Kenya. Home-based (door-to-door) screening occurred in March 2010 and community-based screening in November 2011. HIV counselors were trained to screen for diabetes and hypertension in the home-based screening with local district hospital based staff conducting the community-based screening. Participants \u3e18 years old qualified for screening in both groups. Counselors referred all participants with a systolic blood pressure (SBP) ≥ 160 mmHg and/or a random blood glucose ≥ 7 mmol/L (126 mg/dL) to a local clinic for follow-up. Differences in likelihood of screening positive between the two strategies were compared using Fischer\u27s Exact Test. Logistic regression models were used to identify factors associated with the likelihood of following-up after a positive screening. RESULTS: There were 236 participants in home-based screening: 13 (6%) had a SBP ≥ 160 mmHg, and 54 (23%) had a random glucose ≥ 7 mmol/L. There were 346 participants in community-based screening: 35 (10%) had a SBP ≥ 160 mmHg, and 27 (8%) had a random glucose ≥ 7 mmol/L. Participants in community-based screening were twice as likely to screen positive for hypertension compared to home-based screening (OR=1.93, P=0.06). In contrast, participants were 3.5 times more likely to screen positive for a random blood glucose ≥ 7 mmol/L with home-based screening (OR=3.51, P CONCLUSION: Community- or home-based screening for diabetes and hypertension in LMICs is feasible. Due to low rates of follow-up, screening efforts in rural settings should focus on linking cases to care

Stakes sensitivity and credit rating: a new challenge for regulators

The ethical practices of credit rating agencies (CRAs), particularly following the 2008 financial crisis, have been subject to extensive analysis by economists, ethicists, and policymakers. We raise a novel issue facing CRAs that has to do with a problem concerning the transmission of epistemic status of ratings from CRAs to the beneficiaries of the ratings (investors, etc.), and use it to provide a new challenge for regulators. Building on recent work in philosophy, we argue that since CRAs have different stakes than the beneficiaries of the ratings in the ratings being accurate, what counts as knowledge (and as having ‘epistemic status’) concerning credit risk for a CRA may not count as knowledge (as having epistemic status) for the beneficiary. Further, as it stands, many institutional investors (pension funds, insurance companies, etc.) are bound by law to make some of their investment decisions dependent on the ratings of officially recognized CRAs. We argue that the observation that the epistemic status of ratings does not transmit from CRAs to beneficiaries makes salient a new challenge for those who think current regulation regarding the CRAs is prudentially justified, namely, to show that the harm caused by acting on a rating that does not have epistemic status for beneficiaries is compensated by the benefit from them acting on a CRA rating that does have epistemic status for the CRA. Unlike most other commentators, therefore, we offer a defeasible reason to drop references to CRAs in prudential regulation of the financial industry

Principles of cartilage tissue engineering in TMJ reconstruction

Diseases and defects of the temporomandibular joint (TMJ), compromising the cartilaginous layer of the condyle, impose a significant treatment challenge. Different regeneration approaches, especially surgical interventions at the TMJ's cartilage surface, are established treatment methods in maxillofacial surgery but fail to induce a regeneration ad integrum. Cartilage tissue engineering, in contrast, is a newly introduced treatment option in cartilage reconstruction strategies aimed to heal cartilaginous defects. Because cartilage has a limited capacity for intrinsic repair, and even minor lesions or injuries may lead to progressive damage, biological oriented approaches have gained special interest in cartilage therapy. Cell based cartilage regeneration is suggested to improve cartilage repair or reconstruction therapies. Autologous cell implantation, for example, is the first step as a clinically used cell based regeneration option. More advanced or complex therapeutical options (extracorporeal cartilage engineering, genetic engineering, both under evaluation in pre-clinical investigations) have not reached the level of clinical trials but may be approached in the near future. In order to understand cartilage tissue engineering as a new treatment option, an overview of the biological, engineering, and clinical challenges as well as the inherent constraints of the different treatment modalities are given in this paper

Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel

<p>Abstract</p> <p>Background</p> <p>Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect.</p> <p>Methods</p> <p>Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks.</p> <p>Results</p> <p>The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p < 0.012). The relative expression level of type-2 collagen, aggrecan, and SOX9 mRNAs was significantly greater in Group II than in the control group (p < 0.023).</p> <p>Conclusions</p> <p>This study demonstrated that spontaneous hyaline cartilage regeneration can be induced <it>in vivo </it>in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.</p

Management of work-relevant upper limb disorders: a review

Background Upper limb disorders (ULDs) are clinically challenging and responsible for considerable work loss. There is a need to determine effective approaches for their management. Aim To determine evidence-based management strategies for work-relevant ULDs and explore whether a biopsychosocial approach is appropriate. Methods Literature review using a best evidence synthesis. Data from articles identified through systematic searching of electronic databases and citation tracking were extracted into evidence tables. The information was synthesized into high-level evidence statements, which were ordered into themes covering classification/diagnosis, epidemiology, associations/risks and management/treatment, focusing on return to work or work retention and taking account of distinctions between non-specific complaints and specific diagnoses. Results Neither biomedical treatment nor ergonomic workplace interventions alone offer an optimal solution; rather, multimodal interventions show considerable promise, particularly for occupational outcomes. Early return to work, or work retention, is an important goal for most cases and may be facilitated, where necessary, by transitional work arrangements. The emergent evidence indicates that successful management strategies require all the players to be onside and acting in a coordinated fashion; this requires engaging employers and workers to participate. Conclusions The biopsychosocial model applies: biological considerations should not be ignored, but psychosocial factors are more influential for occupational outcomes. Implementation of interventions that address the full range of psychosocial issues will require a cultural shift in the way the relationship between upper limb complaints and work is conceived and handled. Dissemination of evidence-based messages can contribute to the needed cultural shift

Urocortin protects chondrocytes from NO-induced apoptosis: a future therapy for osteoarthritis?

Osteoarthritis (OA) is characterized by a loss of joint mobility and pain resulting from progressive destruction and loss of articular cartilage secondary to chondrocyte death and/ or senescence. Certain stimuli including nitric oxide (NO) and the pro-inflammatory cytokine tumor necrosis factor α (TNF-α have been implicated in this chondrocyte death and the subsequent accelerated damage to cartilage. In this study, we demonstrate that a corticotrophin releasing factor (CRF) family peptide, urocortin (Ucn), is produced by a human chondrocyte cell line, C-20/A4, and acts both as an endogenous survival signal and as a cytoprotective agent reducing the induction of apoptosis by NO but not TNF-α when added exogenously. Furthermore, treatment with the NO donor S-nitroso-N-acetyl-D-L-penicillamine upregulates chondrocyte Ucn expression, whereas treatment with TNF-α does not. The chondroprotective effects of Ucn are abolished by both specific ligand depletion (with an anti-Ucn antibody) and by CRF receptor blockade with the pan-CRFR antagonist α-helical CRH(9-41). CRFR expression was confirmed by reverse transcription-PCR with subsequent amplicon sequence analysis and demonstrates that C-20/A4 cells express both CRFR1 and CRFR2, specifically CRFR1α and CRFR2β. Protein expression of these receptors was confirmed by western blotting. The presence of both Ucn and its receptors in these cells, coupled with the induction of Ucn by NO, suggests the existence of an endogenous autocrine/paracrine chondroprotective mechanism against stimuli inducing chondrocyte apoptosis via the intrinsic/mitochondrial pathway

Trauma induces apoptosis in human thoracolumbar intervertebral discs

BACKGROUND: Vertebral fractures resulting from high energy trauma often comprise the risk of posttraumatic degenerative changes in the affected intervertebral discs (IVD). Particularly in conservatively treated patients, or in cases after implant removal of an exclusively posterior stabilization, consecutive disc degeneration and the associated functional losing of the spinal segment clearly represent detrimental treatment results. In this regard, apoptosis of IVD cells has been suggested to be involved in the critical changes of the extracellular matrix. METHODS: To investigate whether fractures of the vertebrae induce apoptosis in the affected IVD, disc tissue from patients (n = 17) undergoing open reduction and internal fixation of thoracolumbar spine fractures were analysed in regards to caspase activity, apoptosis-receptor expression levels and gene expression of apoptosis-regulating proteins such as Bax and Bcl-2. Healthy IVD tissue (n = 3) obtained from patients undergoing surgical resection of adjacent vertebrae were used as control samples. RESULTS: In contrast to healthy control IVD tissues, samples from traumatic thoracolumbar IVD showed positive TUNEL staining and a significant increase of caspase-3/7 activity. Interestingly, analyses of the initiator caspase-8 and -9 revealed significantly increased activation levels compared to control values, suggesting the coexistent activation of both the extrinsic (receptor-mediated) and intrinsic (mitochondria-mediated) apoptosis pathway. Accordingly, expression levels of the Fas receptor (FasR) mRNA were significantly increased. Although the TNF receptor I (TNFR I) was only slightly upregulated, corresponding TNFα from trauma IVD presented significantly increased mRNA expression values. Furthermore, traumatic IVD cells demonstrated significantly reduced expression of the mitochondria-bound anti-apoptotic Bcl-2, thereby maintaining baseline transcriptional levels of the pro-apoptotic Bax protein when compared to control IVD cells. CONCLUSION: Our data suggest that thoracolumbar fractures induce early caspase-dependent apoptosis in IVD cells of the affected intervertebral disc, in part, by downregulation of the anti-apoptotic protein Bcl-2 (intrinsic apoptosis pathway), as well as signalling via the death receptor complex (TNFR I and FasR)

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal