A pathologic twoâ way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity

Lung fibrosis is characterised by the accumulation of extracellular matrix within the lung and is secondary to both known and unknown aetiologies. This accumulation of scar tissue limits gas exchange causing respiratory insufficiency. The pathogenesis of lung fibrosis is poorly understood, but immunologicâ based treatments have been largely ineffective. Despite this, accumulating evidence suggests that innate immune cells and receptors play important modulatory roles in the initiation and propagation of the disease. Paradoxically, while innate immune signalling may be important for the pathogenesis of fibrosis, there is also evidence to suggest that innate immune function against pathogens may be impaired, leading to dysregulated and/or impaired host defence. This review summarises the evidence for this pathologic twoâ way street, highlights new concepts of pathogenesis and recommends future directions for research emphasis.Innate immunity has been shown to promote the development of lung injury and fibrosis through a myriad of mechanisms. New information also suggests that the fibrotic milieu can impair the function of innate immune cells, leading to further infection, dysbiosis and fibrotic progression.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149765/1/cti21065.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149765/2/cti21065_am.pd

Growth faltering in rural Gambian children after four decades of interventions: a retrospective cohort study

Background Growth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identifi cation of eff ective interventions remains a challenge. Methods We analysed the eff ect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defi ned growth faltering as fall in Z score between 3 months and 21 months of age. Findings We noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5–44·0) for underweight and 57·1% (51·9–62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score –1·36, 95% CI –1·44 to –1·27, weight-for-age Z score –1·20, –1·28 to –1·11, and head circumference Z score –0·51, –0·59 to –0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0–33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight). Interpretation A combination of nutrition-sensitive and nutrition-specifi c interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions

Microbes and the malnourished child.

New research implicates a dysfunctional gut microbiome in the etiology of severe childhood malnutrition and confirms a role for antibiotics in its treatment

Thresholds of socio-economic and environmental conditions necessary to escape from childhood malnutrition: a natural experiment in rural Gambia.

BACKGROUND: Childhood malnutrition remains highly prevalent in low-income countries, and a 40% reduction in under-5 year stunting is WHO's top Global Target 2025. Disappointingly, meta-analyses of intensive nutrition interventions reveal that they generally have low efficacy at improving growth. Unhygienic environments also contribute to growth failure, but large WASH Benefits and SHINE trials of improved water, sanitation and hygiene (WASH) recently reported no benefits to child growth. METHODS: To explore the thresholds of socio-economic status (SES) and living standards associated with malnutrition, we exploited a natural experiment in which the location of our research centre within a remote rural village created a wide diversity of wealth, education and housing conditions within the same ecological setting and with free health services to all. A composite SES score was generated by grading occupation, education, income, water and sanitation, and housing and families were allocated to 5 groups (SES1 = highest). SES ranged from very poor subsistence-farming villagers to post graduate staff with overseas training. Nutritional status at 24 m was obtained from clinic records for 230 children and expressed relative to WHO Growth Standards. RESULTS: Height-for-age (HAZ) and weight-for-age (WAZ) Z-scores were strongly predicted by SES group. HAZ varied from - 0.67 to - 2.23 (P < 0.001) and WAZ varied from - 0.90 to - 1.64 (P < 0.001), from SES1 to SES5, respectively. Weight-for-height (WHZ) showed no gradient. Children in SES1 showed greater dispersion so were further divided in a post hoc analysis. Children resident in Western housing on the research compound (SES1A) had HAZ = + 0.68 and WAZ = + 0.36. The residual gradient between those in SES1B and SES5 spanned only 0.65 Z-score for HAZ (- 1.58 to - 2.23) and was not significant for WAZ or WHZ. CONCLUSIONS: The large difference in growth between children in SES1A living in Western-type housing and SES1B children living in the village, and the very shallow gradient between SES1B and SES5, implies a very high SES threshold before stunting and underweight will be eliminated. This may help to explain the lack of efficacy of the recent WASH interventions and points to the need for what is termed 'Transformative WASH'. Good quality housing, with piped water into the home, may be key to eliminating malnutrition

Prevalence of rickets-like bone deformities in rural Gambian children.

The aim of this study was to estimate the burden of childhood rickets-like bone deformity in a rural region of West Africa where rickets has been reported in association with a low calcium intake. A population-based survey of children aged 0.5-17.9 years living in the province of West Kiang, The Gambia was conducted in 2007. 6221 children, 92% of those recorded in a recent census, were screened for physical signs of rickets by a trained survey team with clinical referral of suspected cases. Several objective measures were tested as potential screening tools. The prevalence of bone deformity in children <18.0 years was 3.3%. The prevalence was greater in males (M = 4.3%, F = 2.3%, p < 0.001) and in children <5.0 years (5.7%, M = 8.3%, F = 2.9%). Knock-knee was more common (58%) than bow-leg (31%) or windswept deformity (9%). Of the 196 examined clinically, 36 were confirmed to have a deformity outside normal variation (47% knock-knee, 53% bow-leg), resulting in more conservative prevalence estimates of bone deformity: 0.6% for children <18.0 years (M = 0.9%, F = 0.2%), 1.5% for children < 5.0 years (M = 2.3%, F = 0.6%). Three of these children (9% of those with clinically-confirmed deformity, 0.05% of those screened) had active rickets on X-ray at the time of medical examination. This emphasises the difficulties in comparing prevalence estimates of rickets-like bone deformities from population surveys and clinic-based studies. Interpopliteal distance showed promise as an objective screening measure for bow-leg deformity. In conclusion, this population survey in a rural region of West Africa with a low calcium diet has demonstrated a significant burden of rickets-like bone deformity, whether based on physical signs under survey conditions or after clinical examination, especially in boys < 5.0 years

Equatorial Pacific productivity changes near the Eocene-Oligocene boundary

There is general agreement that productivity in high latitudes increased in the late Eocene and remained high in the early Oligocene. Evidence for both increased and decreased productivity across the Eocene-Oligocene transition (EOT) in the tropics has been presented, usually based on only one paleoproductivity proxy and often in sites with incomplete recovery of the EOT itself. A complete record of the Eocene-Oligocene transition was obtained at three drill sites in the eastern equatorial Pacific Ocean (ODP Site 1218 and IODP Sites U1333 and U1334). Four paleoproductivity proxies that have been examined at these sites, together with carbon and oxygen isotope measurements on early Oligocene planktonic foraminifera, give evidence of ecologic and oceanographic change across this climatically important boundary. Export productivity dropped sharply in the basal Oligocene (~33.7�Ma) and only recovered several hundred thousand years later; however, overall paleoproductivity in the early Oligocene never reached the average levels found in the late Eocene and in more modern times. Changes in the isotopic gradients between deep- and shallow-living planktonic foraminifera suggest a gradual shoaling of the thermocline through the early Oligocene that, on average, affected accumulation rates of barite, benthic foraminifera, and opal, as well as diatom abundance near 33.5�Ma. An interval with abundant large diatoms beginning at 33.3�Ma suggests an intermediate thermocline depth, which was followed by further shoaling, a dominance of smaller diatoms, and an increase in average primary productivity as estimated from accumulation rates of benthic foraminifera

An Adaptive Decision Framework for the Conservation of a Threatened Plant

This is the publisher's version, also available electronically from http://www.fwspubs.org/.Mead's milkweed Asclepias meadii, a long-lived perennial herb of tallgrass prairie and glade communities of the central United States, is a species designated as threatened under the U.S. Endangered Species Act. Challenges to its successful management include the facts that much about its life history is unknown, its age at reproductive maturity is very advanced, certain life stages are practically unobservable, its productivity is responsive to unpredictable environmental events, and most of the known populations occur on private lands unprotected by any legal conservation instrument. One critical source of biological uncertainty is the degree to which fire promotes growth and reproductive response in the plant. To aid in its management, we developed a prototype population-level state-dependent decision-making framework that explicitly accounts for this uncertainty and for uncertainties related to stochastic environmental effects and vital rates. To parameterize the decision model, we used estimates found in the literature, and we analyzed data from a long-term monitoring program where fates of individual plants were observed through time. We demonstrate that different optimal courses of action are followed according to how one believes that fire influences reproductive response, and we show that the action taken for certain population states is informative for resolving uncertainty about competing beliefs regarding the effect of fire. We advocate the use of a model-predictive approach for the management of rare populations, particularly when management uncertainty is profound. Over time, an adaptive management approach should reduce uncertainty and improve management performance as predictions of management outcome generated under competing models are continually informed and updated by monitoring data

The Iowa Homemaker vol.1, no.9

Table of Contents Aunt Sarah’s Portrait and the Frame that Matched by Ruth Safford, page 1 Hymns for Christmas Day and Every Day by Eda Lord Murphy, page 2 Buffet Service Makes Holiday Entertainment Easy by Helen Paschal, page 3 The Art of Framing and Hanging Pictures by Joanna M. Hansen, page 4 Christmas Gifts From My Christmas Paint Shop by Mildred Elder, page 5 Home Made Toys for Tiny Tots by Clara Jordan, page 6 By Her Clothes You Shall Know Her by Ruth Spencer, page 7 Why Not a Christmas Plum Pudding Sale? by Willetta Moore, page 8 Christmas Sweets You Will Want to Make by Beth Bailey, page 8 A Unique Nutrition Clinic by Ione Johnson, page 1