98 research outputs found
Responsible translation of stem cell research: An assessment of clinical trial registration and publications
We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials
Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth
BACKGROUND: Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth.
METHODS AND RESULTS: Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension.
CONCLUSIONS: Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage
Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.
OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model
Differential effect of Coriolus versicolor (Yunzhi) extract on cytokine production by murine lymphocytes in vitro
Abstract Being one of the commonly used Chinese medicinal herbs, Coriolus versicolor (CV), also named as Yunzhi, was known to possess both anti-tumor and immunopotentiating activities. The present study aimed to investigate the in vitro immunomodulatory effect of a standardized ethanol-water extract prepared from CV on the proliferation of murine splenic lymphocytes using the MTT assay, and the production of six T helper (Th)-related cytokines using the enzyme-linked immunosorbent assay (ELISA) technique. The results showed that the CV extract significantly augmented the proliferation of murine splenic lymphocytes in a time-and dose-dependent manner, maximally by 2.4-fold. Moreover, the production of two Th1-related cytokines, including interleukin (IL)-2 and IL-12, in culture supernatants from the CV extract-activated lymphocytes was prominently upregulated at 48 and 72 h. Positive correlations were found between the levels of these two cytokines and the MTT-based proliferative response. In contrast, the production of two other Th1-related cytokines, including interferon (IFN)-g and IL-18, was significantly augmented only at 24 h, but not at 48 and 72 h. On the other hand, the levels of two Th2-related cytokines such as IL-4 and IL-6 were undetectable in the culture supernatants of lymphocytes treated with the CV extract. The CV extract was suggested to be a lymphocyte mitogen by differentially enhancing the production of Th1-related cytokines.
The Major Surface-Associated Saccharides of Klebsiella pneumoniae Contribute to Host Cell Association
Analysing the pathogenic mechanisms of a bacterium requires an understanding of the composition of the bacterial cell surface. The bacterial surface provides the first barrier against innate immune mechanisms as well as mediating attachment to cells/surfaces to resist clearance. We utilised a series of Klebsiella pneumoniae mutants in which the two major polysaccharide layers, capsule and lipopolysaccharide (LPS), were absent or truncated, to investigate the ability of these layers to protect against innate immune mechanisms and to associate with eukaryotic cells. The capsule alone was found to be essential for resistance to complement mediated killing while both capsule and LPS were involved in cell-association, albeit through different mechanisms. The capsule impeded cell-association while the LPS saccharides increased cell-association in a non-specific manner. The electrohydrodynamic characteristics of the strains suggested the differing interaction of each bacterial strain with eukaryotic cells could be partly explained by the charge density displayed by the outermost polysaccharide layer. This highlights the importance of considering not only specific adhesin:ligand interactions commonly studied in adherence assays but also the initial non-specific interactions governed largely by the electrostatic interaction forces
Differences between seven measures of self-reported numbers of clients of female sex workers in southern India: implications for individual- and population-level analysis.
Quantifying sexual activity of sub-populations with high-risk sexual behaviour is important in understanding HIV epidemiology. This study examined inconsistency of seven outcomes measuring self-reported clients per month (CPM) of female sex workers (FSWs) in southern India and implications for individual/population-level analysis. Multivariate negative binomial regression was used to compare key social/environmental factors associated with each outcome. A transmission dynamics model was used to assess the impact of differences between outcomes on population-level FSW/client HIV prevalence. Outcomes based on 'clients per last working day' produced lower estimates than those based on 'clients per typical day'. Although the outcomes were strongly correlated, their averages differed by approximately two-fold (range 39.0-79.1 CPM). The CPM measure chosen did not greatly influence standard epidemiological 'risk factor' analysis. Differences across outcomes influenced HIV prevalence predictions. Due to this uncertainty, we recommend basing population-based estimates on the range of outcomes, particularly when assessing the impact of interventions
Demonstration of Ignition Radiation Temperatures in Indirect-Drive Inertial Confinement Fusion Hohlraums
Intraoperative graft tensioning alters viscoelastic but not failure behaviours of rabbit medial collateral ligament autografts
Assessment and incidence of salivary leak following laryngectomy
OBJECTIVES/HYPOTHESIS: To determine the incidence and risk factors of pharyngocutaneous fistula formation in patients undergoing either primary or salvage laryngectomies and evaluate the role of barium esophagram in these patients. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of 259 patients who underwent total laryngectomy between 2003 and 2009 at our institution were reviewed. Risk factors for fistula formation were analyzed, including primary treatment modality, comorbidities, and operative details, which included use of a free flap for closure, concurrent neck dissections, margin status, and preoperative tracheostomy. The length of time until leak, postoperative swallow study results, and fistula management strategies were also assessed. RESULTS: Fifty-five patients developed a pharyngocutaneous fistula (overall incidence, 21%) in a median time of 12 days (range, 4–105 days). Twenty of these patients underwent laryngectomy as their initial treatment modality, and 35 had failed previous radiotherapy. Fistula formation was significantly higher in salvage surgery patients (P = .03), particularly those with hypothyroidism (P < .0002). A barium swallow performed at approximately 1 week after laryngectomy demonstrated a sensitivity of 26% with a specificity of 94%. Sixty-two percent of the fistulas healed with conservative measures only. CONCLUSIONS: Our data confirmed that previous radiotherapy and hypothyroidism, particularly in salvage laryngectomy patients, are important significant predictors of postoperative pharyngocutaneous fistula. The use of a postoperative barium swallow in these patients may be useful but was not found to be highly sensitive in predicting who will develop a clinically evident leak and should be used with caution
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