Maternal effects on offspring size in a natural population of the viviparous tsetse fly

1. Theory predicts that mothers should adaptively adjust reproductive investment depending on current reserves and future reproductive opportunities. Females in better intrinsic state, or with more resources, should invest more in current reproduction than those with fewer resources. Across the lifespan, investment may increase as future reproductive opportunities decline, yet may also decline with reductions in intrinsic state. 2. Across many species, larger mothers produce larger offspring, but there is no theoretical consensus on why this is so. This pattern may be driven by variation in maternal state such as nutrition, yet few studies measure both size and nutritional state or attempt to tease apart confounding effects of size and age. 3. Viviparous tsetse flies (Glossina species) offer an excellent system to explore patterns of reproductive investment: females produce large, single offspring sequentially over the course of their relatively long life. Thus, per-brood reproductive effort can be quantified by offspring size. 4. While most tsetse reproduction research has been conducted on laboratory colonies, maternal investment was investigated in this study using a unique field method where mothers were collected as they deposited larvae, allowing simultaneous mother-offspring measurements under natural conditions. 5. It was found that larger mothers and those with a higher fat content produced larger offspring, and there was a trend for older mothers to produce slightly larger offspring. 6. The present results highlight the importance of measuring maternal nutritional state, rather than size alone, when considering maternal investment in offspring. Implications for understanding vector population dynamics are also discussed.The study received financial assistance from the World Health Organisation’s Special Programme for Research and Training in Tropical Diseases (TDR) through a grant agreement with the International Development Research Centre of Canada(106905–00) and from DFID/RCUK programme on Zoonoses and Emerging Livestock Systems (ZELS, BBSRC grant no. BB/L019035/1). S. English is supported by the Royal Society of London

The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

Explaining the effects of a multifaceted intervention to improve inpatient care in rural Kenyan hospitals -- interpretation based on retrospective examination of data from participant observation, quantitative and qualitative studies

<p>Abstract</p> <p>Background</p> <p>We have reported the results of a cluster randomized trial of rural Kenyan hospitals evaluating the effects of an intervention to introduce care based on best-practice guidelines. In parallel work we described the context of the study, explored the process and perceptions of the intervention, and undertook a discrete study on health worker motivation because this was felt likely to be an important contributor to poor performance in Kenyan public sector hospitals. Here, we use data from these multiple studies and insights gained from being participants in and observers of the intervention process to provide our explanation of how intervention effects were achieved as part of an effort to better understand implementation in low-income hospital settings.</p> <p>Methods</p> <p>Initial hypotheses were generated to explain the variation in intervention effects across place, time, and effect measure (indicator) based on our understanding of theory and informed by our implementation experience and participant observations. All data sources available for hospitals considered as cases for study were then examined to determine if hypotheses were supported, rejected, or required modification. Data included transcriptions of interviews and group discussions, field notes and that from the detailed longitudinal quantitative investigation. Potentially useful explanatory themes were identified, discussed by the implementing and research team, revised, and merged as part of an iterative process aimed at building more generic explanatory theory. At the end of this process, findings were mapped against a recently reported comprehensive framework for implementation research.</p> <p>Results</p> <p>A normative re-educative intervention approach evolved that sought to reset norms and values concerning good practice and promote 'grass-roots' participation to improve delivery of correct care. Maximal effects were achieved when this strategy and external support supervision helped create a soft-contract with senior managers clarifying roles and expectations around desired performance. This, combined with the support of facilitators acting as an expert resource and 'shop-floor' change agent, led to improvements in leadership, accountability, and resource allocation that enhanced workers' commitment and capacity and improved clinical microsystems. Provision of correct care was then particularly likely if tasks were simple and a good fit to existing professional routines. Our findings were in broad agreement with those defined as part of recent work articulating a comprehensive framework for implementation research.</p> <p>Conclusions</p> <p>Using data from multiple studies can provide valuable insight into how an intervention is working and what factors may explain variability in effects. Findings clearly suggest that major intervention strategies aimed at improving child and newborn survival in low-income settings should go well beyond the fixed inputs (training, guidelines, and job aides) that are typical of many major programmes. Strategies required to deliver good care in low-income settings should recognize that this will need to be co-produced through engagement often over prolonged periods and as part of a directive but adaptive, participatory, information-rich, and reflective process.</p

Variability in the use of pulse oximeters with children in Kenyan hospitals: A mixed-methods analysis.

BACKGROUND: Pulse oximetry, a relatively inexpensive technology, has the potential to improve health outcomes by reducing incorrect diagnoses and supporting appropriate treatment decisions. There is evidence that in low- and middle-income countries, even when available, widespread uptake of pulse oximeters has not occurred, and little research has examined why. We sought to determine when and with which children pulse oximeters are used in Kenyan hospitals, how pulse oximeter use impacts treatment provision, and the barriers to pulse oximeter use. METHODS AND FINDINGS: We analyzed admissions data recorded through Kenya's Clinical Information Network (CIN) between September 2013 and February 2016. We carried out multiple imputation and generated multivariable regression models in R. We also conducted interviews with 30 healthcare workers and staff from 14 Kenyan hospitals to examine pulse oximetry adoption. We adapted the Integrative Model of Behavioural Prediction to link the results from the multivariable regression analyses to the qualitative findings. We included 27,906 child admissions from 7 hospitals in the quantitative analyses. The median age of the children was 1 year, and 55% were male. Three-quarters had a fever, over half had a cough; other symptoms/signs were difficulty breathing (34%), difficulty feeding (34%), and indrawing (32%). The most common diagnoses were pneumonia, diarrhea, and malaria: 45%, 35%, and 28% of children, respectively, had these diagnoses. Half of the children obtained a pulse oximeter reading, and of these, 10% had an oxygen saturation level below 90%. Children were more likely to receive a pulse oximeter reading if they were not alert (odds ratio [OR]: 1.30, 95% confidence interval (CI): 1.09, 1.55, p = 0.003), had chest indrawing (OR: 1.28, 95% CI: 1.17, 1.40, p < 0.001), or a very high respiratory rate (OR: 1.27, 95% CI: 1.13, 1.43, p < 0.001), as were children admitted to certain hospitals, at later time periods, and when a Paediatric Admission Record (PAR) was used (OR PAR used compared with PAR not present: 2.41, 95% CI: 1.98, 2.94, p < 0.001). Children were more likely to be prescribed oxygen if a pulse oximeter reading was obtained (OR: 1.42, 95% CI:1.25, 1.62, p < 0.001) and if this reading was below 90% (OR: 3.29, 95% CI: 2.82, 3.84, p < 0.001). The interviews indicated that the main barriers to pulse oximeter use are inadequate supply, broken pulse oximeters, and insufficient training on how, when, and why to use pulse oximeters and interpret their results. According to the interviews, variation in pulse oximeter use between hospitals is because of differences in pulse oximeter availability and the leadership of senior doctors in advocating for pulse oximeter use, whereas variation within hospitals over time is due to repair delays. Pulse oximeter use increased over time, likely because of the CIN's feedback to hospitals. When pulse oximeters are used, they are sometimes used incorrectly and some healthcare workers lack confidence in readings that contradict clinical signs. The main limitations of the study are that children with high levels of missing data were not excluded, interview participants might not have been representative, and the interviews did not enable a detailed exploration of differences between counties or across senior management groups. CONCLUSIONS: There remain major challenges to implementing pulse oximetry-a cheap, decades old technology-into routine care in Kenya. Implementation requires efficient and transparent procurement and repair systems to ensure adequate availability. Periodic training, structured clinical records that include prompts, the promotion of pulse oximetry by senior doctors, and monitoring and feedback might also support pulse oximeter use. Our findings can inform strategies to support the use of pulse oximeters to guide prompt and effective treatment, in line with the Sustainable Development Goals. Without effective implementation, the potential benefits of pulse oximeters and possible hospital cost-savings by targeting oxygen therapy might not be realized

Antimicrobial activity of two South African honeys produced from indigenous Leucospermum cordifolium and Erica species on selected micro-organisms

<p>Abstract</p> <p>Background</p> <p>Honey has been shown to have wound healing properties which can be ascribed to its antimicrobial activity. The antimicrobial activity can be effective against a broad spectrum of bacterial species especially those of medical importance. It has also been shown that there is considerable variation in the antimicrobial potency of different types of honey, which is impossible to predict. With this in mind we tested the antimicrobial activity of honeys produced from plants grown in South Africa for their antibacterial properties on selected standard strains of oral micro-organisms.</p> <p>Methods</p> <p>The honeys used were produced from the blossoms of <it>Eucalyptus cladocalyx </it>(Bluegum) trees, an indigenous South African plant <it>Leucospermum cordifolium </it>(Pincushion), a mixture of wild heather shrubs, mainly <it>Erica </it>species (Fynbos) and a <it>Leptospermum scoparium </it>(Manuka) honey. Only pure honey which had not been heated was used. The honeys were tested for their antimicrobial properties with a broth dilution method.</p> <p>Results</p> <p>Although the honeys produced some inhibitory effect on the growth of the micro-organisms, no exceptionally high activity occurred in the South African honeys. The carbohydrate concentration plays a key role in the antimicrobial activity of the honeys above 25%. However, these honeys do contain other antimicrobial properties that are effective against certain bacterial species at concentrations well below the hypertonic sugar concentration. The yeast <it>C. albicans </it>was more resistant to the honeys than the bacteria. The species <it>S. anginosus </it>and <it>S. oralis </it>were more sensitive to the honeys than the other test bacteria.</p> <p>Conclusion</p> <p>The honeys produced from indigenous wild flowers from South Africa had no exceptionally high activity that could afford medical grade status.</p

Summary of data reported to CDC's national automated biosurveillance system, 2008

<p>Abstract</p> <p>Background</p> <p>BioSense is the US national automated biosurveillance system. Data regarding chief complaints and diagnoses are automatically pre-processed into 11 broader syndromes (e.g., respiratory) and 78 narrower sub-syndromes (e.g., asthma). The objectives of this report are to present the types of illness and injury that can be studied using these data and the frequency of visits for the syndromes and sub-syndromes in the various data types; this information will facilitate use of the system and comparison with other systems.</p> <p>Methods</p> <p>For each major data source, we summarized information on the facilities, timeliness, patient demographics, and rates of visits for each syndrome and sub-syndrome.</p> <p>Results</p> <p>In 2008, the primary data sources were the 333 US Department of Defense, 770 US Veterans Affairs, and 532 civilian hospital emergency department facilities. Median times from patient visit to record receipt at CDC were 2.2 days, 2.0 days, and 4 hours for these sources respectively. Among sub-syndromes, we summarize mean 2008 visit rates in 45 infectious disease categories, 11 injury categories, 7 chronic disease categories, and 15 other categories.</p> <p>Conclusions</p> <p>We present a systematic summary of data that is automatically available to public health departments for monitoring and responding to emergencies.</p

Measuring health-related quality of life for child maltreatment: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Child maltreatment causes substantial morbidity and mortality in the U.S. Morbidity associated with child maltreatment can reduce health-related quality of life. Accurately measuring the reduction in quality of life associated with child maltreatment is essential to the economic evaluation of educational programs and interventions to reduce the incidence of child maltreatment. The objective of this study was to review the literature for existing approaches and instruments for measuring quality-of-life for child maltreatment outcomes.</p> <p>Methods</p> <p>We reviewed the current literature to identify current approaches to valuing child maltreatment outcomes for economic evaluations. We also reviewed available preference-based generic QOL instruments (EQ-5D, HUI, QWB, SF-6D) for appropriateness in measuring change in quality of life due to child maltreatment.</p> <p>Results</p> <p>We did not identify any studies that directly evaluated quality-of-life in maltreated children. We identified 4 studies that evaluated quality of life for adult survivors of child maltreatment and 8 studies that measured quality-of-life for pediatric injury not related to child maltreatment. No study reported quality-of-life values for children younger than age 3.</p> <p>Currently available preference-based QOL instruments (EQ-5D, HUI, QWB, SF-6D) have been developed primarily for adults with the exception of the Health Utilities Index. These instruments do not include many of the domains identified as being important in capturing changes in quality of life for child maltreatment, such as potential for growth and development or psychological sequelae specific to maltreatment.</p> <p>Conclusion</p> <p>Recommendations for valuing preference-based quality-of-life for child maltreatment will vary by developmental level and type of maltreatment. In the short-term, available multi-attribute utility instruments should be considered in the context of the type of child maltreatment being measured. However, if relevant domains are not included in existing instruments or if valuing health for children less than 6 years of age, direct valuation with a proxy respondent is recommended. The choice of a proxy respondent is not clear in the case of child maltreatment since the parent may not be a suitable proxy. Adult survivors should be considered as appropriate proxies. Longer-term research should focus on identifying the key domains for measuring child health and the development of preference-based quality-of-life instruments that are appropriate for valuing child maltreatment outcomes.</p

Targeting Lysophosphatidic Acid Signaling Retards Culture-Associated Senescence of Human Marrow Stromal Cells

Marrow stromal cells (MSCs) isolated from mesenchymal tissues can propagate in vitro to some extent and differentiate into various tissue lineages to be used for cell-based therapies. Cellular senescence, which occurs readily in continual MSC culture, leads to loss of these characteristic properties, representing one of the major limitations to achieving the potential of MSCs. In this study, we investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite in membrane phospholipid synthesis, on the senescence program of human MSCs. We show that MSCs preferentially express the LPA receptor subtype 1, and an abrogation of the receptor engagement with the antagonistic compound Ki16425 attenuates senescence induction in continually propagated human MSCs. This anti-aging effect of Ki16425 results in extended rounds of cellular proliferation, increased clonogenic potential, and retained plasticity for osteogenic and adipogenic differentiation. Expressions of p16Ink4a, Rb, p53, and p21Cip1, which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling. Disruption of this signaling pathway was accompanied by morphological changes such as cell thinning and elongation as well as actin filament deformation through decreased phosphorylation of focal adhesion kinase. Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G0 phase, of the cell cycle. Collectively, these results highlight the potential of pharmacological intervention against LPA signaling for blunting senescence-associated loss of function characteristic of human MSCs

Predictors of sun protection behaviours and sunburn among Australian adolescents

BACKGROUND: Excessive sun exposure and sunburn increase individuals' risk of skin cancer. It is especially important to prevent sunburn in childhood due to the higher relative risk of skin cancer across the life span compared to risk associated with sunburn episodes experienced later in life. This study examined demographic and attitudinal factors associated with engagement in a range of sun protection behaviours (wearing a hat, wearing protective clothing, staying in the shade, and staying indoors during the middle of the day) and the frequency of sunburn among Western Australian adolescents to provide insights of relevance for future sun protection campaigns. METHODS: Cross-sectional telephone surveys were conducted annually with Western Australians between 2005/06 and 2014/15. The results from 4150 adolescents aged 14-17 years were used to conduct a path analysis of factors predicting various sun protection behaviours and sunburn. RESULTS: Significant primary predictors of the sun protection behaviours included in the study were skin type (sun sensitivity), gender, tanning-related attitudes and behaviours, and perceived relevance of public service advertisements that advocate sun protection. Of the four sun protection behaviours investigated, staying in the shade and staying indoors during the middle of the day were associated with a lower frequency of sunburn. CONCLUSION: There is a particular need to target sun protection messages at adolescent males who are less likely to engage in the most effective sun protection behaviours and demonstrate an increased propensity to experience sunburn. The results suggest that such future sun protection messages should include a focus on the importance of staying in the shade or indoors during periods of high UV radiation to increase awareness of the efficacy of these methods of avoiding skin cancer