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

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File includes: January 2017 Volume 4, Issue 7 February 2017 Volume 4, Issue 8 March 2017 Volume 4, Issue 9 April 2017 Volume 4, Issue 10 May 2017 Volume 4, Issue 11 June 2017 Volume 4, Issue 12 July 2017 Volume 5, Issue 1 August 2017 Volume 5, Issue 2 September 2017 Volume 5, Issue 3 October 2017 Volume 5, Issue 4 November 2017 Volume 5, Issue 5 December 2017 Volume 5, Issue

Socio-economic differences and health seeking behaviour for the diagnosis and treatment of malaria: a case study of four local government areas operating the Bamako initiative programme in south-east Nigeria

BACKGROUND: Malaria is one of the leading causes of mortality and morbidity in Nigeria. It is not known how user fees introduced under the Bamako Initiative (BI) system affect healthcare seeking among different socio-economic groups in Nigeria for diagnosis and treatment of malaria. Reliable information is needed to initiate new policy thrusts to protect the poor from the adverse effect of user fees. METHODS: Structured questionnaires were used to collect information from 1594 female household primary care givers or household head on their socio-economic and demographic status and use of malaria diagnosis and treatment services. Principal components analysis was used to create a socio-economic status index which was decomposed into quartiles and chi-square for trends was used to calculate for any statistical difference. RESULTS: The study showed that self diagnosis was the commonest form of diagnosis by the respondents. This was followed by diagnosis through laboratory tests, community health workers, family members and traditional healers. The initial choice of care for malaria was a visit to the patent medicine dealers for most respondents. This was followed by visit to the government hospitals, the BI health centres, traditional medicine healers, private clinics, community health workers and does nothing at home. Furthermore, the private health facilities were the initial choice of treatment for the majority with a decline among those choosing them as a second source of care and an increase in the utilization of public health facilities as a second choice of care. Self diagnosis was practiced more by the poorer households while the least poor used the patent medicine dealers and community health workers less often for diagnosis of malaria. The least poor groups had a higher probability of seeking treatment at the BI health centres (creating equity problem in BI), hospitals, and private clinics and in using laboratory procedures. The least poor also used the patent medicine dealers and community health workers less often for the treatment of malaria. The richer households complained more about poor staff attitude and lack of drugs as their reasons for not attending the BI health centres. The factors that encourage people to use services in BI health centres were availability of good services, proximity of the centres to the homes and polite health workers. CONCLUSIONS: Factors deterring people from using BI centres should be eliminated. The use of laboratory services for the diagnosis of malaria by the poor should be encouraged through appropriate information, education and communication which at the long run will be more cost effective and cost saving for them while devising means of reducing the equity gap created. This could be done by granting a properly worked out and implemented fee exemptions to the poor or completely abolishing user fees for the diagnosis and treatment of malaria in BI health centres

Virus Movements on the Plasma Membrane Support Infection and Transmission between Cells

How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus–host interactions upstream of infectious entry offer new perspectives for anti-viral interference

Synoptic-to-planetary scale wind variability enhances phytoplankton biomass at ocean fronts

In nutrient-limited conditions, phytoplankton growth at fronts is enhanced by winds, which drive upward nutrient fluxes via enhanced turbulent mixing and upwelling. Hence, depth-integrated phytoplankton biomass can be 10 times greater at isolated fronts. Using theory and two-dimensional simulations with a coupled physical-biogeochemical ocean model, this paper builds conceptual understanding of the physical processes driving upward nutrient fluxes at fronts forced by unsteady winds with timescales of 4–16 days. The largest vertical nutrient fluxes occur when the surface mixing layer penetrates the nutricline, which fuels phytoplankton in the mixed layer. At a front, mixed layer deepening depends on the magnitude and direction of the wind stress, cross-front variations in buoyancy and velocity at the surface, and potential vorticity at the base of the mixed layer, which itself depends on past wind events. Consequently, mixing layers are deeper and more intermittent in time at fronts than outside fronts. Moreover, mixing can decouple in time from the wind stress, even without other sources of physical variability. Wind-driven upwelling also enhances depth-integrated phytoplankton biomass at fronts; when the mixed layer remains shallower than the nutricline, this results in enhanced subsurface phytoplankton. Oscillatory along-front winds induce both oscillatory and mean upwelling. The mean effect of oscillatory vertical motion is to transiently increase subsurface phytoplankton over days to weeks, whereas slower mean upwelling sustains this increase over weeks to months. Taken together, these results emphasize that wind-driven phytoplankton growth is both spatially and temporally intermittent and depends on a diverse combination of physical processes.DBW was supported by the National Science Foundation postdoctoral research fellowship program, award number 1421125. J.R.T. was supported by the Natural Environment Research Council, award NE/J010472/1

The impact of user fees on access to health services in low- and middle-income countries.

BACKGROUND: Following an international push for financing reforms, many low- and middle-income countries introduced user fees to raise additional revenue for health systems. User fees are charges levied at the point of use and are supposed to help reduce 'frivolous' consumption of health services, increase quality of services available and, as a result, increase utilisation of services. OBJECTIVES: To assess the effectiveness of introducing, removing or changing user fees to improve access to care in low-and middle-income countries SEARCH STRATEGY: We searched 25 international databases, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group's Trials Register, CENTRAL, MEDLINE and EMBASE. We also searched the websites and online resources of international agencies, organisations and universities to find relevant grey literature. We conducted the original searches between November 2005 and April 2006 and the updated search in CENTRAL (DVD-ROM 2011, Issue 1); MEDLINE In-Process & Other Non-Indexed Citations, Ovid (January 25, 2011); MEDLINE, Ovid (1948 to January Week 2 2011); EMBASE, Ovid (1980 to 2011 Week 03) and EconLit, CSA Illumina (1969 - present) on the 26th of January 2011. SELECTION CRITERIA: We included randomised controlled trials, interrupted time-series studies and controlled before-and-after studies that reported an objective measure of at least one of the following outcomes: healthcare utilisation, health expenditures, or health outcomes. DATA COLLECTION AND ANALYSIS: We re-analysed studies with longitudinal data. We computed price elasticities of demand for health services in controlled before-and-after studies as a standardised measure. Due to the diversity of contexts and outcome measures, we did not perform meta-analysis. Instead, we undertook a narrative summary of evidence. MAIN RESULTS: We included 16 studies out of the 243 identified. Most of the included studies showed methodological weaknesses that hamper the strength and reliability of their findings. When fees were introduced or increased, we found the use of health services decreased significantly in most studies. Two studies found increases in health service use when quality improvements were introduced at the same time as user fees. However, these studies have a high risk of bias. We found no evidence of effects on health outcomes or health expenditure. AUTHORS' CONCLUSIONS: The review suggests that reducing or removing user fees increases the utilisation of certain healthcare services. However, emerging evidence suggests that such a change may have unintended consequences on utilisation of preventive services and service quality. The review also found that introducing or increasing fees can have a negative impact on health services utilisation, although some evidence suggests that when implemented with quality improvements these interventions could be beneficial. Most of the included studies suffered from important methodological weaknesses. More rigorous research is needed to inform debates on the desirability and effects of user fees

Ergonomic evaluation of commercially available operator lifts for farmers with disabilities

Individuals in the agricultural population who are impacted by mobility restrictions resulting from strokes, arthritis, amputations, back injuries, and other medical conditions are capable of safely returning to work through the appropriate application of assistive or rehabilitation technology. The purpose of this study was to develop and administer a systems approach for evaluating ergonomic and safety issues related to the application of commercially available operator lifts used on agricultural and other offroad machinery to provide a means for operators with restricted mobility to gain access to the operator\u27s station. Input from operator lift users, objective analysis and a panel of experts were used to gain a clearer perspective of commercially available operator lift systems. Unstable seats, awkward transfers and the need for fall arresting devices were identified as concerns through on-site visits of operator lift users. Objective analysis methods, including the use of an operator lift users\u27 questionnaire, were used to identify key issues, such as usability of the operator lift controllers and using the operator lifts in emergency situations, which needed to be addressed. An expert panel used lift evaluation tools to identify problems with installation, wiring and troubleshooting related to operator lift systems. Based upon feedback from 60 operator lift users, spinal cord injuries were reported by 42 (75%) of the users. Forty-three (76%) of the users had full use of their upper arms. Only nine (17%) of the lift users were able to access the same piece of machinery after their injury and before they had a lift. Eight (16%) of the 49 individuals that purchased a commercially manufactured lift reported a minor injury or near injury while using their lift. Similarly, one (14%) of the seven individuals that had a locally manufactured or homemade lift reported a minor injury while using their lift. Even though it appeared that the level of safety was the same for commercially manufactured and locally fabricated lifts, commercially manufactured lifts appeared to have fewer hazards associated with them. The findings from this study can be used to justify the safety and applicability of operator lifts in agriculture, aid in the design and fabrication of future operator lifts, and develop an industrial standard on the design, fabrication and testing of operator lifts for use on off-road equipment