Mixing ratios of volatile organic compounds (VOCs) in the atmosphere of Karachi, Pakistan

Mixing ratios of carbon monoxide (CO), methane (CH4), non-methane hydrocarbons, halocarbons and alkyl nitrates (a total of 72 species) were determined for 78 whole air samples collected during the winter of 1998-1999 in Karachi, Pakistan. This is the first time that volatile organic compound (VOC) levels in Karachi have been extensively characterized. The overall air quality of the urban environment was determined using air samples collected at six locations throughout Karachi. Methane (6.3ppmv) and ethane (93ppbv) levels in Karachi were found to be much higher than in other cities that have been studied. The very high CH4 levels highlight the importance of natural gas leakage in Karachi. The leakage of liquefied petroleum gas contributes to elevated propane and butane levels in Karachi, although the propane and butane burdens were lower than in other cities (e.g., Mexico City, Santiago). High levels of benzene (0.3-19ppbv) also appear to be of concern in the Karachi urban area. Vehicular emissions were characterized using air samples collected along the busiest thoroughfare of the city (M.A. Jinnah Road). Emissions from vehicular exhaust were found to be the main source of many of the hydrocarbons reported here. Significant levels of isoprene (1.2ppbv) were detected at the roadside, and vehicular exhaust is estimated to account for about 20% of the isoprene observed in Karachi. 1,2-Dichloroethane, a lead scavenger added to leaded fuel, was also emitted by cars. The photochemical production of ozone (O3) was calculated for CO and the various VOCs using the Maximum Incremental Reactivity (MIR) scale. Based on the MIR scale, the leading contributors to O3 production in Karachi are ethene, CO, propene, m-xylene and toluene. © 2002 Elsevier Science Ltd. All rights reserved

Squamous cell carcinoma of the scrotum in a Nigerian: case report

Squamous cell carcinoma of the scrotum is rare and to the best of our knowledge has never been reported from Nigeria. We report on a case thought to be occupation-related in a 42-year old Nigerian taxi driver who had previously been an automobile mechanic and later a long-haul truck driver. He presented with a stage D disease and only palliation was feasible

Malaria control under the Taliban regime: insecticide-treated net purchasing, coverage, and usage among men and women in eastern Afghanistan

BACKGROUND: Scaling up insecticide-treated mosquito net (ITN) coverage is a key malaria control strategy even in conflict-affected countries 12. Socio-economic factors influence access to ITNs whether subsidized or provided free to users. This study examines reported ITN purchasing, coverage, and usage in eastern Afghanistan and explores women's access to health information during the Taliban regime (1996-2001). This strengthens the knowledge base on household-level health choices in complex-emergency settings. METHODS: Fifteen focus group discussions (FGDs) and thirty in-depth interviews were conducted with men and women from ITN-owning and non-owning households. FGDs included rank ordering, pile sorting and focused discussion of malaria knowledge and ITN purchasing. Interviews explored general health issues, prevention and treatment practices, and women's malaria knowledge and concerns. Seven key informant interviews with health-related workers and a concurrent survey of 200 ITN-owning and 214 non-owning households were used to clarify or quantify findings. RESULTS: Malaria knowledge was similar among men and women and ITN owners and non-owners. Women reported obtaining health information through a variety of sources including clinic staff, their husbands who had easier access to information, and particularly female peers. Most participants considered ITNs very desirable, though not usually household necessities. ITN owners reported more household assets than non-owners. Male ITN owners and non-owners ranked rugs and ITNs as most desired, while women ranked personal assets such as jewellery highest. While men were primarily responsible for household decision-making and purchasing, older women exerted considerable influence. Widow-led and landless households reported most difficulties purchasing ITNs. Most participants wanted to buy ITNs only if they could cover all household members. When not possible, preferential usage was given to women and children. CONCLUSIONS: Despite restricted access to health facilities and formal education, Afghan women were surprisingly knowledgeable about the causes of malaria and the value of ITNs in prevention. Inequities in ITN usage were noted between rather than within households, with some unable to afford even one ITN and others not wanting ITNs unless all household members could be protected. Malaria knowledge thus appears a lesser barrier to ITN purchasing and coverage in eastern Afghanistan than are pricing and distribution strategies

Proteolytic shedding of the prion protein via activation of metallopeptidase ADAM10 reduces cellular binding and toxicity of amyloid-β oligomers

The cellular prion protein (PrPC) is a key neuronal receptor for amyloid-β oligomers (AβO), mediating their neurotoxicity, which contributes to the neurodegeneration in Alzheimer's disease (AD). Similarly to the amyloid precursor protein (APP), PrPC is proteolytically cleaved from the cell surface by a disintegrin and metalloprotease, ADAM10. We hypothesized that ADAM10-modulated PrPC shedding would alter the cellular binding and cytotoxicity of AβO. Here, we found that in human neuroblastoma cells, activation of ADAM10 with the muscarinic agonist carbachol promotes PrPC shedding and reduces the binding of AβO to the cell surface, which could be blocked with an ADAM10 inhibitor. Conversely, siRNA-mediated ADAM10 knockdown reduced PrPC shedding and increased AβO binding, which was blocked by the PrPC-specific antibody 6D11. The retinoic acid receptor analog acitretin, which up-regulates ADAM10, also promoted PrPC shedding and decreased AβO binding in the neuroblastoma cells and in human induced pluripotent stem cell (iPSC)-derived cortical neurons. Pretreatment with acitretin abolished activation of Fyn kinase and prevented an increase in reactive oxygen species caused by AβO binding to PrPC Besides blocking AβO binding and toxicity, acitretin also increased the non-amyloidogenic processing of APP. However, in the iPSC-derived neurons, Aβ and other amyloidogenic processing products did not exhibit a reciprocal decrease upon acitretin treatment. These results indicate that by promoting the shedding of PrPC in human neurons, ADAM10 activation prevents the binding and cytotoxicity of AβO, revealing a potential therapeutic benefit of ADAM10 activation in AD

The National Women's Health Study: assembly and description of a population-based reproductive cohort

BACKGROUND: Miscarriage is a common event but is remarkably difficult to measure in epidemiological studies. Few large-scale population-based studies have been conducted in the UK. METHODS: This was a population-based two-stage postal survey of reproductive histories of adult women living in the United Kingdom in 2001, sampled from the electronic electoral roll. In Stage 1 a short "screening" questionnaire was sent to over 60,000 randomly selected women in order to identify those aged 55 and under who had ever been pregnant or ever attempted to achieve a pregnancy, from whom a brief reproductive history was requested. Stage 2 involved a more lengthy questionnaire requesting detailed information on every pregnancy (and fertility problems), and questions relating to socio-demographic, behavioural and other factors for the most recent pregnancy in order to examine risk factors for miscarriage. Data on stillbirth, multiple birth and maternal age are compared to national data in order to assess response bias. RESULTS: The response rate was 49% for Stage 1 and 73% for the more targeted Stage 2. A total of 26,050 questionnaires were returned in Stage 1. Of the 17,748 women who were eligible on the grounds of age, 27% reported that they had never been pregnant and had never attempted to conceive a child. The remaining 13,035 women reported a total of 30,661 pregnancies. Comparison of key reproductive indicators (stillbirth and multiple birth rates and maternal age at first birth) with national statistics showed that the data look remarkably similar to the general population. CONCLUSIONS: This study has enabled the assembly of a large population-based dataset of women's reproductive histories which appears unbiased compared to the general UK population and which will enable investigation of hard-to-measure outcomes such as miscarriage and infertility

Malaria risk factors in north-east Tanzania

BACKGROUND: Understanding the factors which determine a household's or individual's risk of malaria infection is important for targeting control interventions at all intensities of transmission. Malaria ecology in Tanzania appears to have reduced over recent years. This study investigated potential risk factors and clustering in face of changing infection dynamics. METHODS: Household survey data were collected in villages of rural Muheza district. Children aged between six months and thirteen years were tested for presence of malaria parasites using microscopy. A multivariable logistic regression model was constructed to identify significant risk factors for children. Geographical information systems combined with global positioning data and spatial scan statistic analysis were used to identify clusters of malaria. RESULTS: Using an insecticide-treated mosquito net of any type proved to be highly protective against malaria (OR 0.75, 95% CI 0.59-0.96). Children aged five to thirteen years were at higher risk of having malaria than those aged under five years (OR 1.71, 95% CI 1.01-2.91). The odds of malaria were less for females when compared to males (OR 0.62, 95% CI 0.39-0.98). Two spatial clusters of significantly increased malaria risk were identified in two out of five villages. CONCLUSIONS: This study provides evidence that recent declines in malaria transmission and prevalence may shift the age groups at risk of malaria infection to older children. Risk factor analysis provides support for universal coverage and targeting of long-lasting insecticide-treated nets (LLINs) to all age groups. Clustering of cases indicates heterogeneity of risk. Improved targeting of LLINs or additional supplementary control interventions to high risk clusters may improve outcomes and efficiency as malaria transmission continues to fall under intensified control

Risk Factors for Extended Duration of Acute Diarrhea in Young Children

Objective and Background: We sought to identify predictors of extended duration of diarrhea in young children, which contributes substantially to the nearly 1 1/2 million annual diarrheal deaths globally. Methods: We followed 6-35 month old Nepalese children enrolled in the placebo-arm of a randomized controlled trial with 391 episodes of acute diarrhea from the day they were diagnosed until cessation of the episode. Using multiple logistic regression analysis, we identified independent risk factors for having diarrhea for more than 7 days after diagnosis. Results: Infants had a 17 (95% CI 3.5, 83)-fold and toddlers (12 to 23 month olds) a 9.9 (95% CI 2.1, 47)-fold higher odds of having such illness duration compared to the older children. Not being breastfed was associated with a 9.3 (95% CI 2.4, 35.7)-fold increase in the odds for this outcome. The odds also increased with increasing stool frequency. Furthermore, having diarrhea in the monsoon season also increased the risk of prolonged illness. Conclusion: We found that high stool frequency, not being breastfed, young age and acquiring diarrhea in the rainy season were risk factors for prolonged diarrhea. In populations such as ours, breastfeeding may be the most important modifiable risk factor for extended duration of diarrhea

Genetic Variation in the Proximal Promoter of ABC and SLC Superfamilies: Liver and Kidney Specific Expression and Promoter Activity Predict Variation

Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (−250 to +50 bp) and flanking 5′ sequence of 107 transporters in the ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (π) was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response

Pleiotropic Effects of DDT Resistance on Male Size and Behaviour

Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. Here we tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. We also assessed relative aggression in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature