Exploring agricultural land-use and childhood malaria associations in sub-Saharan Africa

Agriculture in Africa is rapidly expanding but with this comes potential disbenefits for the environment and human health. Here, we retrospectively assess whether childhood malaria in sub-Saharan Africa varies across differing agricultural land uses after controlling for socio-economic and environmental confounders. Using a multi-model inference hierarchical modelling framework, we found that rainfed cropland was associated with increased malaria in rural (OR 1.10, CI 1.03 – 1.18) but not urban areas, while irrigated or post flooding cropland was associated with malaria in urban (OR 1.09, CI 1.00 – 1.18) but not rural areas. In contrast, although malaria was associated with complete forest cover (OR 1.35, CI 1.24 – 1.47), the presence of natural vegetation in agricultural lands potentially reduces the odds of malaria depending on rural-urban context. In contrast, no associations with malaria were observed for natural vegetation interspersed with cropland (veg-dominant mosaic). Agricultural expansion through rainfed or irrigated cropland may increase childhood malaria in rural or urban contexts in sub-Saharan Africa but retaining some natural vegetation within croplands could help mitigate this risk and provide environmental co-benefits

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma.

BackgroundAlkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross-sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning.MethodSeventy-four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7-day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25-hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti-inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)-a validated measure of disease progression stratified by age.ResultsFifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid-upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as "clinically undernourished." Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti-inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score.ConclusionAKU patients are at risk of protein depletion associated with a "perfect storm" of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated

Changes in body weight and food choice in those attempting smoking cessation: a cluster randomised controlled trial

<p><b>Background:</b> Fear of weight gain is a barrier to smoking cessation and significant cause of relapse for many people. The provision of nutritional advice as part of a smoking cessation programme may assist some in smoking cessation and perhaps limit weight gain. The aim of this study was to determine the effect of a structured programme of dietary advice on weight change and food choice, in adults attempting smoking cessation.</p> <p><b>Methods:</b> Cluster randomised controlled design. Classes randomised to intervention commenced a 24-week intervention, focussed on improving food choice and minimising weight gain. Classes randomised to control received "usual care".</p> <p><b>Results:</b> Twenty-seven classes in Greater Glasgow were randomised between January and August 2008. Analysis, including those who continued to smoke, showed that actual weight gain and percentage weight gain was similar in both groups. Examination of data for those successful at giving up smoking showed greater mean weight gain in intervention subjects (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not significant (p=0.23, 95% CI -0.9 to 3.5). In comparison to baseline improved consumption of fruit and vegetables and breakfast cereal were reported in the intervention group. A higher percentage of control participants continued smoking (74% vs. 66%).</p> <p><b>Conclusions:</b> The intervention was not successful at minimising weight gain in comparison to control but was successful in facilitating some sustained improvements in the dietary habits of intervention participants. Improved quit rates in the intervention group suggest that continued contact with advisors may have reduced anxieties regarding weight gain and encouraged cessation despite weight gain. Research should continue in this area as evidence suggests that the negative effects of obesity could outweigh the health benefits achieved through reductions in smoking prevalence.</p&gt

Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods-wavelet analysis, economic analysis, statistical and disease transmission modelling-we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens

Policy challenges for the pediatric rheumatology workforce: Part III. the international situation

Survival dominates current pediatric global health priorities. Diseases of poverty largely contribute to overall mortality in children under 5 years of age. Infectious diseases and injuries account for 75% of cause-specific mortality among children ages 5-14 years. Twenty percent of the world's population lives in extreme poverty (income below US $1.25/day). Within this population, essential services and basic needs are not met, including clean water, sanitation, adequate nutrition, shelter, access to health care, medicines and education. In this context, musculoskeletal disease comprises 0.1% of all-cause mortality in children ages 5-14 years. Worldwide morbidity from musculoskeletal disease remains generally unknown in the pediatric age group. This epidemiologic data is not routinely surveyed by international agencies, including the World Health Organization. The prevalence of pediatric rheumatic diseases based on data from developed nations is in the range of 2,500 - 3,000 cases per million children. Developing countries' needs for musculoskeletal morbidity are undergoing an epidemiologic shift to chronic conditions, as leading causes of pediatric mortality are slowly quelled

Granulocyte-colony stimulating factor (G-CSF) for stroke: an individual patient data meta-analysis

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p=0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p=0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p=0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

An experimental study on the response of blanket bog vegetation and water tables to ditch blocking

We studied the effect of ditch blocking on vegetation composition and water-table depths in a blanket peatland. Measurements were made for a period of four years (water tables) and five years (vegetation) in the inter-ditch areas of three experimental treatments: (i) open ditches, (ii) ditches blocked with closely-spaced dams and (iii) ditches partially infilled with peat and blocked with dams. It is often assumed that ditch blocking will lead to an increase in the abundance of Sphagnum and, potentially, a reduction in the abundance of sedges, particularly the cotton grasses. However, our data show no treatment effects on the abundance of either group. We did find an effect of time, with the abundance of both sedges and Sphagnum spp. varying significantly between some years. For the sedges there was no systematic change over time, while for the Sphagnum spp. abundance tended to increase through the study period. This systematic change was not related to a measure of the vigour of the sedges, although vigour was lower towards the end of the study compared to the beginning. Our vegetation data are consistent with our water-table data. As with plant type abundance, we did not find any statistically significant differences in water-table depths between treatments, both for annual averages and summer averages. We comment on why ditch blocking does not seem to have affected water tables and vegetation composition at our study site

Endoscopic resection of giant lipoma mimicking colonic neoplasm initially presenting with massive haemorrhage: a case report

Lipomas of the colon are benign tumors that rarely occur. Their size ranges from 2 mm to several cm. They are usually asymptomatic but occasionally they present with clinical manifestations depending on tumor size, localization and complications, which often lead to diagnostic difficulty. A 40-year-old man presented with massive rectal haemorrhage. During colonoscopy a giant polyp of over 50 mm in its bigger diameter, with a thick stalk of 2 cm, located in the transverse colon, was revealed. Endoscopic resection was performed with success. Histologic examination demonstrated a giant lipoma. In this report discussion over endoscopic resection of colonic lipomas mimicking neoplasms is also performed