Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates with chronic immune activation.

The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive individuals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4(+) central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.

Evaluation of nurse providers of comprehensive abortion care using MVA in Nepal.

BACKGROUND: Although Nepal's maternal mortality ratio has fallen over the past decade, unsafe abortion remains a leading cause of maternal morbidity and mortality. A key strategy for improving access to safe abortion services is to train mid-level providers such as nurses in comprehensive abortion care (CAC). The Family Health Division of the Nepal Ministry of Health trained an initial cohort of 96 nurses to provide first trimester CAC services using manual vacuum aspiration (MVA) between September 2006 and July 2009. This study evaluates the acceptability and quality of CAC services provided by trained nurses in Nepal. METHODS: Five assessments were used to evaluate post-training service provision on CAC: facility logbooks registry, nurse provider interviews, facility assessments, facility manager interviews and procedure observation checklists. Ninety-two nurses from 50 facilities participated in the evaluation. Descriptive statistics are reported. RESULTS: Overall, 5,600 women received CAC services from 42 facilities where nurses were providing services between June 2009 and April 2010. Complications were experienced by 68 surgical abortion clients (1.6%) and 12 medical abortion clients (1.2%). All nurses reported that clients were happy to receive care from them, and 67% of facility managers reported that clients preferred nurse providers over physicians or had no preference. Facility managers and nurses reported a need for additional support, including further training and improved drug and equipment supply. CONCLUSIONS: Trained nurses provide high quality CAC services in Nepal. Additional support in the form of facilitative supervision and training should be considered to strengthen CAC service provision.

Increasing access to safe abortion services through auxiliary nurse midwives trained as skilled birth attendants.

BACKGROUND: The use of medical abortion methods was approved by Department of Health Services in 2009 and introduced in hospitals and a few primary health centres (PHCs). Access would increase if services were available at health post level and provided by auxiliary nurse midwives trained as skilled birth attendants. Evidence from South Africa, Bangladesh, Nepal and Vietnam show that mid-level health workers can provide medical abortion safely. OBJECTIVES: To determine the best way to implement the new strategies of medical abortion into the existing health system of Nepal; and to facilitate its full-scale implementation, monitoring and evaluation. METHODS: An implementation research involving a baseline study, implementation phase and end line study was done in ten districts covering five development regions from July 2010 to June 2011. Both qualitative and quantitative methods were used. RESULTS: Of 1,799 medical abortion clients who received service, 46% were disadvantaged Janjati, 14% were Dalit, 42% were upper caste groups and rest were advantaged Janjati (7%), Muslim (1%) and others. 14% were referred by female community health volunteers and 56% were referred by others. Complication rate of 0.3% was well below acceptable levels. Condom use increased from 8% to 28% by the end of study. Use of Pills, Depo, intra uterine devices and implants also increased, but use of long acting family planning methods was negligible. CONCLUSIONS: This model should be replicated nationwide at health posts and sub-health posts where auxiliary nurse midwives are available 24 hours/day. Focus should be given first to those areas where access is difficult, time consuming and costly.

Precipitation and temperature effects on mortality and lactation parameters of dairy cattle in California.

Data from 3 commercial rendering companies located in different regions of California were analyzed from September 2003 through August 2005 to examine the relationship of dairy calf and cow mortality to monthly average daily temperature and total monthly precipitation respectively. Yearly average mortality varied between rendering regions from 2.1 to 8.1% for mature cows. The relationship between cow and calf monthly mortality and monthly average daily temperature was U-shaped. Overall, months with average daily temperatures less than 14 and greater than 24 degrees C showed substantial increases in both calf and cow mortality with calf mortality being more sensitive to changes in these temperature ranges than cow mortality. Temperature changes were reflected in a 2-fold difference between the minimum and maximum mortality in cows and calves. Precipitation showed a weak effect with calf mortality and no effect with cow mortality. Data from Dairy Herd Improvement Association were used from 112 California herds tested over a 24-mo period to examine the relationship of milk production and quality with monthly average daily temperature and monthly precipitation. Somatic cell count and percent milk fat were either weakly or not associated with monthly average daily temperature and total monthly precipitation. However, total monthly precipitation was negatively associated with test day milk per milking cow regardless of the dairy's geographical location. Housing-specific associations for test day milk per milking cow were greater for total monthly precipitation than monthly average daily temperature, with the strongest negative association seen for dairies that do not provide shelter for cows. This suggests that providing suitable housing for lactating dairy cattle may ameliorate the precipitation-associated decrease in test day milk per milking cow.

A methodical study of shape changes in human oral cells perturbed by a simulated orthodontic strain in vitro.

Cells are known to alter their shape as a response to physical and chemical changes. Mechanical loads applied to teeth produced cellular perturbations resulting in orthodontic movement. An in vitro model was developed to simulate the in vivo strain of orthodontic movement. Calibrated forces were applied to human periodontal ligament cells and buccal mucosal fibroblasts (controls). A biaxial strain-producing device was used to stretch vital cells growth on flexible polytetrafluorethylene membranes. In addition, a new cell adhesive, Cell Tak, was employed to examine the effect of an adhesive substrate on the cellular response to two known loads. The shape changes of unstrained (control) and strained cells were evaluated by time-lapse telemicroscopy, and plots of time-dependent alterations in area and shape were recorded. The fusiform cells became more rounded over a given time of up to 1400 s. The responses appeared to be independent of cell type, the strain employed, and the presence of cell adhesive. Scanning electron microscopy demonstrated, irrespective of cell type, that the surface of stressed cells produced a striking number of microvilli as compared with the relatively smooth-surfaced controls.

Determination of stress levels and profiles in the periodontal ligament by means of an improved three-dimensional finite element model for various types of orthodontic and natural force systems.

This study was undertaken to investigate the stress-strain levels and distribution within the periodontal ligament for various types of physiological and orthodontic force systems, assuming that the bone resorption process, leading to tooth movements, is partly controlled by those conditions. Two finite element models were developed, simulating a full and partial mandibular morphology, respectively. Both models were based on morphology and physical parameters of human autopsy material. The effect of changing material parameters and structure, type of boundary conditions, calculation method and fineness of the model on the stress levels and profiles in the periodontal ligament was evaluated by a series of tests. A structure optimization technique was used to investigate the load bearing characteristics of the mandible and the influence of the anisotropic material properties of both the mandible and the segment. A 'multiple modelling' technique based on both the mandible and the segment was developed to test various types of boundary conditions in the analysis of the segment. Results presented as 'stress profiles' showing the correlation between the applied force system and the stress distribution in the periodontal ligament, based on the improved finite element models, were established.

Material parameters and stress profiles within the periodontal ligament.

Levels and profiles of initial stress in the periodontal ligament after application of various force systems were studied. Two finite-element models, based on sections of human autopsy material, were developed to simulate one full and one partial mandible. The validity of the finite-element model was improved by identification of material parameters; the mechanical properties of the tissue were described by means of strain-gauge measurements of initial tooth movements in human autopsy material. The multiple modeling technique, in which data from a coarse global model are transferred to a more detailed one, was used to identify bone structure and boundary conditions. Parameters known to influence the results were varied to establish the validity of the finite-element model. Iterative calculation methods were used to gain stable results. However, optimizing features of the bone structure and boundary conditions did not influence the results significantly. The elastic stiffness of the periodontal ligament was determined to 0.07 MPa and tau = 0.49 (tau being the Poisson's ratio). Stress profiles were obtained for various force systems--as in tipping, translation, and root movement. As we expected, there was a marked variation in the stress distribution from cervix to apex when tipping forces were applied. Bodily movement of the tooth produced an almost uniform stress distribution; root movement produced stress patterns opposite to those observed during tipping; and masticatory forces alone produced stress patterns almost identical to those achieved by masticatory force in combination with orthodontic forces.

A device for the application of known simulated orthodontic forces to human cells in vitro.

Connective tissues are responsive to mechanical forces. In orthodontic tooth movement it appears that the periodontal ligament (PDL) is the source of a pleuropotential cell population and extracellular matrix structure which translates mechanical perturbation information into a host of cellular events. These include proliferation, repair, differentiation, and shape change. We have designed, built, and tested a simple, adaptable machine which enables us to examine molecular changes or events in the cell nucleus, cell membrane, and the cytoskeleton of any eukasytic cell that will adhere to a membrane. These responses to clinically simulated forces applied to an in vitro system can be measured.

Buccal mucosa fibroblasts and periodontal ligament cells perturbed by tensile stimuli in vitro.

Human buccal mucosa fibroblasts and periodontal ligament cells grown in tissue culture were subjected to tensile forces approximating those used for orthodontic bodily tooth movement. The cells were synchronized into pre S phase and positively tested for response to nonmechanical physical stimuli. Two-dimensional gel analysis and immunohistochemical analysis of the three cytoskeletal components showed a lack of response. Similar negative results were found when the cells were perturbed in the presence of substance P. We hypothesize that perhaps these cells respond more readily to injury, a secondary effect of the forces of tooth movement, than to tensile forces.

Purification and identification of murine epidermal dendritic cells: flow cytometry and immunogold labeling.

We report on application of flow cytometric and immunogold labeling techniques to purify and identify two types of murine epidermal dendritic cells: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy 1+-dEC). After density centrifugation of epidermal cell (EC) suspensions through Ficoll gradients. IA-positive LC and Thy 1+-dEC are labeled with monoclonal antibodies (fluorescein-conjugated anti-IAd for LC and anti-Thy 1.2-biotin, followed by avidin-phycoerythrin, for Thy 1+-dEC). The fluorescence-activated cell sorter (FACS) is then used to obtain 95-98% pure populations of these dendritic cells with a yield of 2-4 X 10(6) cells and a viability of 80-90%. A post-fixation, pre-embedding immunogold labeling technique using 15 nm and 40 nm colloidal gold particles is employed to identify LC and Thy 1+-dEC, respectively, to confirm the purity of the sorting and to estimate the number of IA antigenic sites per LC. With transmission electron microscopy, ultrastructural morphology of sorted LC is preserved; however, Birbeck granules are markedly diminished compared to the pre-sorted population of LC. In contrast, characteristic dense-core granules are readily visualized in sorted Thy 1+-dEC. Purification of epidermal dendritic cells by flow cytometry may be a useful technique to employ in functional studies of epidermal dendritic cells.

Favourable levels of cardio-vascular health and risk indicators during childhood and adolescence.

This paper is concerned with favourable levels of constitutional cardio-vascular health indicators during childhood and adolescence. A cross-sectional randomised sample of healthy Czechoslovakian children was investigated, because this population is habituated to a favourable life style. Twenty girls and 20 boys at ages 8, 12 and 16 years were recruited to the study. Statistical data for means and standard deviations are presented with regard to maximal aerobic power, haemodynamic variables such as arterial blood pressure, heart rate at submaximal and maximal muscular exercise, body fat content, blood lipids including total cholesterol and its fractions, high- and low-density lipo-proteins, fasting triglycerides and the apo-lipo-protein profile. The maximal oxygen uptake in absolute values increased with age in both sexes and the boys appeared to average higher than the girls at each age. When maximal aerobic power was expressed on a total body weight basis, boys appeared to average higher at age 16 years (56 ml X min-1 X kg-1) than girls (45.8 ml X min-1 X kg-1). The highest recorded heart rate for ergometric work averaged close to 200 min-1 in both sexes with no significant age differences. The diastolic blood pressure at rest did not change significantly with age or sex. Serum cholesterol levels were found to decrease significantly after puberty in boys (post-pubertal dip), but in the girls there was found no systematic change in mean values with age. When HDL was expressed as a percentage of total cholesterol there appeared to be no differences related to age and sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulatory and respiratory responses to muscular exercise in Czech and Norwegian children.

This paper presents a comparison between Czech and Norwegian rural healthy children with regard to the functional characteristics of the circulatory and respiratory system based upon work physiological variables and measurements of some pulmonary volumes. The study included randomised samples of boys and girls at the age of 8, 12 and 16 years, 66 Czech boys and 63 girls, 54 Norwegian boys and 57 girls. At the age of 8 years the maximal aerobic power was closely similar in both countries, but in the older age groups the Norwegian children exhibited lower physical fitness. The maximal heart rate was close to 200 min-1 on the average without any sex, age or ethnic differences. In agreement with the higher maximal aerobic power the 12 and 16 year old Czech children had lower submaximal heart rates for the same oxygen uptake than the Norwegian children. The forced vital capacity and forced expiratory volume in one second was significantly higher on the average in Czech than in Norwegian children but the latter, expressed in percent age of the former, averaged 87 to 91% without any sex, age or ethnic differences. The maximal ventilation volumes during muscular exercise reached higher values in Czech than in Norwegian children of the same age, but the mean maximal respiratory rate was close to 60 min-1, being independent of age, sex and cultural differences. During heavy exercise only 40 to 50% of the vital capacity and 45 to 55% of the forced expiratory volume were taken into account and this index of pulmonary function did not differ with sex, age or ethnic differences.

The growth of lung volumes affected by physical performance capacity in boys and girls during childhood and adolescence.

The paper concerns a longitudinal study of the relationship between growth in lung functions in terms of forced vital capacity and forced expiratory volume in 1 s, and the development of maximal aerobic power during the age span from 8-18 years of age. The growth curves of anatomical dimensions for boys and girls were similar to those previously established for Northern European children. The growth in lung volume ended later than the growth in body height. It was found that the growth in lung volume was entirely due to growth in body dimensions, with no additional effect of changes in the development of physical performance capacity.

Leisure time sport activities and maximal aerobic power during late adolescence.

The pattern of leisure time sport activity was estimated by retrospective recalls and expressed in terms of an annual sport activity score. The activity score was related to the development of maximal aerobic power during the period of late adolescence in German children. Both girls and boys reduced their activity pattern from 14 to 18 years of age, boys more than girls. At each age boys were more active than girls. A slight tendency towards better fitness with increased habitual physical activity was noticed, but many sedentary children exhibited a good performance capacity and some children with a high level of leisure time sport activity were characterized by a low level of maximal aerobic power. A statistical analysis revealed that the observed tendency to better fitness with increased habitual physical activity could be explained by an age factor with no additional effect of variation in sport activity score.

Resting- and postexercise-ECG findings in an adult Lapp population.

Resting electrocardiograms were recorded in 412 and postexercise-ECGs in 186 Lapp men and women over the age of 40. Abnormalities in the resting-ECG suggestive of old myocardial infarction by the Minnesota code were found in 7% of the men and in 1% of the women. ST-depression compatible with myocardial ischaemia in the resting-ECG were found in 3% of men aged 40-49 years and in 5% of women of the same age; and increased with age up to 11% and 24% in men and women, respectively, over the age of 60. Postexercise ST-depressions of "ischemic type" were found in 18% of the men and in 13% of the women, but there was no clear age dependence. The frequency of high amplitude R-waves of the left type was high compared with most normal populations, especially in men (29%). These prevalences were very similar to those previously reported in a Finnish population.

Health standards in terms of exercise fitness of school children in urban and rural areas in various European countries.

Health standard in terms of maximal aerobic power has been assessed in representative samples of school children in four European countries, with the object of testing the hypothesis that factors associated with the present days urbanization hamper the developmental process. In Norway and Iceland the exercise fitness of urban living children was stronger than that of children living in scarcely populated areas. In West Germany and Czechoslovakia there appeared a tendency in the same direction though the health standard in some ages was similar for urban and rural living children. The conclusion is consequently clear in as much as no evidence was found that supports the widespread concept that urbanization affects the exercise fitness during growth. On the contrary, urban living seems to enhance the developmental process most likely because the urbanized society stimulates children to vigorous play and sport, thus increasing habitual physical activity. Children living in rural environment become socially isolated, adopt sedentary living habits which subsequently hamper the development of functional characteristics. The maximal aerobic power of the boys and girls in these four European countries was similar when compared on basis on where they are living (urban/rural) except for the Norwegian boys who were considerably superior to the others.

Maximum aerobic power and body composition during the puberty growth period: similarities and differences between children of two European countries.

This report gives results of a longitudinal study of two cohorts of school children in Norway and West-Germany. The rate of growth in body size and composition is identical for the two samples, but different for the two sexes, and follows closely the trend of growth which has been found for North-Europeans in general. Despite of this similarity in growth of anatomical variables the Norwegian children appeared to be superior in their maximum aerobic power at all comparable ages and in both sexes. The differences between means in maximal oxygen uptake varies somewhat with age and sex and are in the range of 5-10%. It is suggested that the mean differences between Norwegian and German children in their exercise and cardio-vascular fitness are brought about by a more physically active behavioural pattern of living in Norway.

Excercise ventilation during the growth spurt period: comparison between two European countries.

The paper provides reference values with regard to pulmonary ventilation responses o progressively increasing bicycling up to the maximal level during the period of growth spurt. Data are based on longitudinal studies or rural Norwegian and German school children. A cluster sampling technique was used, starting with the total pupil-population at Lom in Norway at an age of 8 years, and annual tests were performed until the age of 15 years. In germany a similar pupil-population was tested from age 12 until age 17 years. Functional growth curves giving means and dispersions for ventilation rates, tidal volume, respiratory frequency, ventilatory equivalent and respiratory gas exchange ratio are constructed. Norwegian and German children's developmental processes with regard to the exercise ventilation variables were compared, and revealed no significant differences.

Physical performance capacity of children in Norway. V. The influence of social isolation on the rate of growth in body size and composition and on the achievement in lung function and maximal aerobic power of children in a rural community.

This paper tested the hypothesis that social isolation of children brings about a reduced pattern of habitual physical activity, influences body composition during growth, and hampers development of physical performance capacity. Two cohorts of children were studied, one living at or close to the center, the other living in the periphery of the community of Lom in Southern Norway. The two cohorts of children differed in their patterns of physical behavior, but were otherwise similar in genetic traits, nutrition, and environmental conditions. During a 4-year period the two cohorts of children were tested annually. The center children were leaner, and their maximal oxygen uptake and forced expiratory volume were greater in all years of growth when related to body size.