Atmospheric concentrations of polycyclic aromatic hydrocarbons in the watershed of Lake Victoria, East Africa.

In the first study of its kind in Africa, PAHs were measured in high volume (24 h) air samples collected from two sampling stations, at Kakira and Entebbe (KAK and EBB, respectively) within the Lake Victoria watershed in Uganda, to assess source contributions and generate a baseline reference data set for future studies in the East African region. Sampling was conducted over two periods [2000-2004 (KAK and EBB1) and 2008-2010 (EBB2)]. The samples were extracted by accelerated solvent extraction and analyzed for 30 PAHs by GC-MS. The mean total PAH concentrations (ng/m(3)) were found to be 74.3 (range; 19.3-311, N = 39) for KAK, 56.8 (range; 13.3-126, N = 22) for EBB1 and 33.1 (range; 4.91-108, N = 56) for EBB2. The 3-ringed PAHs were the most predominant group with mean concentrations of 35.9 ng/m(3)(EBB1), 30.5 ng/m(3)(KAK) and 23.2 ng/m(3)(EBB2). Naphthalene had an exceptionally high mean concentration (21.9 ng/m(3)) for KAK compared to 0.44 and 0.39 ng/m(3) in EBB1 and EBB2 respectively, likely due to intensive agricultural operations nearby KAK. Principal component and diagnostic ratio analyses showed that the measured levels of PAHs were associated with mixed sources, combustion of petroleum, and biomass being the major sources.

Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence.

AIMS/HYPOTHESIS: Experimental evidence suggests that the healing of diabetic foot ulcers is affected by psychosocial factors such as distress. We examined this proposal in a prospective study, in which we considered the role of psychological distress and coping style in the healing of diabetic foot ulcers over a 24 week period. We also explored the role of salivary cortisol and matrix metalloproteinases (MMPs) as potential mechanisms. METHODS: For this prospective observational study we recruited 93 (68 men; mean age 60 years) patients with neuropathic or neuroischaemic diabetic foot ulcers from specialist podiatry clinics in secondary care. Clinical and demographic determinants of healing, psychological distress, coping, salivary cortisol and both MMP2 and MMP9 were assessed at baseline. Ulcers were assessed at baseline and at 6, 12 and 24 weeks post-baseline. The primary outcome was ulcer status at 24 weeks, i.e. healed vs not healed. RESULTS: After controlling for clinical and demographic determinants of healing, ulcer healing at 24 weeks was predicted by confrontation coping, but not by depression or anxiety. Patients with unhealed ulcers exhibited greater confrontation coping (model including depression: OR 0.809, 95% CI 0.704-0.929, p = 0.003; model including anxiety: OR 0.810, 95% CI 0.704-0.930, p = 0.003). However, change in ulcer size over the observation period was associated with depression only (p = 0.04, d = 0.31). Healed ulcers by 24 weeks were also associated with lower evening cortisol, higher precursor MMP2 and a greater cortisol awakening response. CONCLUSIONS/INTERPRETATION: Confrontation coping and depression predict ulcer healing. Our preliminary enquiry into biological mechanisms suggests that cortisol and precursor MMP2 may underlie these relationships.

Improvement in the management of acutely poisoned patients using an electronic database, prospective audit and targeted educational intervention.

PROBLEM: The need to improve the clinical assessment and management of acutely poisoned patients presenting to an NHS hospital emergency department (ED). DESIGN: Creation of an electronic clinical toxicology database to prospectively collect all aspects of clinical information on poisoned-patient presentations. Systematic analysis of collated information to identify shortfalls in patient assessment and management. Bimonthly audit meetings, and design and implementation of educational interventions to address identified shortfalls. Ongoing audit to demonstrate continued improvement in patient care. BACKGROUND AND SETTING: ED in tertiary-level inner-city London teaching hospital. Study conducted by staff from the ED and clinical toxicology service. KEY MEASURES FOR IMPROVEMENT: Demonstration of overall reduction in the incidence of predefined shortfalls in patient assessment and management during 12-month study period. STRATEGIES FOR IMPROVEMENT: Targeted educational lectures and case-based clinical scenarios addressing identified deficiencies in the knowledge required to effectively manage poisoned patients. Weekly case-based anonymised feedback report sent electronically to staff involved in caring for poisoned patients. EFFECTS OF CHANGE: Implementation of targeted teaching of ED staff and regular electronic distribution of teaching cases. Between the first and second 6 months of the study, there was a significant increase in the proportion of presentations for which clinical management was graded as "good" (77.6% to 89.4%, p<0.0001) and a significant reduction in the proportion of "major" (9.9% to 5.8%, p = 0.012) and "minor" (12.6% to 4.8%, p<0.0001) shortfalls. LESSONS LEARNT: Systematic collection of clinical information, using a dedicated electronic database and subsequent review and audit of collated data by interested clinicians, enabled design and implementation of targeted educational interventions to address shortfalls in patient management. This process has led to significant improvements in the clinical care of acutely poisoned patients presenting to the ED.

Prevalence and sources of polychlorinated biphenyls in the atmospheric environment of Lake Victoria, East Africa.

The large surface area of Lake Victoria (about 68,800 km2) makes it vulnerable to high atmospheric deposition of chemical pollutants. We present measurements of polychlorinated biphenyls (PCBs) from the lake's atmospheric environment. High volume air (24 h) samples were collected within the northern Lake Victoria watershed in Uganda over two periods; 1999-2004 [at Kakira (KAK) and Entebbe (EBB)] and 2008-2010 (at EBB only). Precipitation samples were also collected monthly during the 2008-2010 period at EBB. Analysis for PCBs was done using GC-µECD in a dual column approach. The ranges of ΣPCB concentrations in the KAK air samples were 154-462 pg m-3 (KAK 1999-2000), 26.7-226 pg m-3 (KAK 2003-2004), 27.0-186 pg m-3 (EBB 2003), 46.8-174 pg m-3 (EBB 2004), 19.2-128 pg m-3 (EBB 2008), 45.8-237 pg m-3 (EBB 2009) and 65.6-244 pg m-3 (EBB 2010). The di-, tri-, tetra- and penta-PCBs were predominant in air sample sets while the tetra- and penta-PCBs were predominant in precipitation samples. The mean flux of ΣPCBs in the precipitation samples was 26.9 ng m-2 (range of 14.8-41.5 and median of 27.5). Concentrations at EBB were lower than those reported elsewhere for urban sites in the East and Central African region. Multivariate analysis and analysis of air mass movements suggested influence of combustion sources on the PCB profiles from the region, especially, from the major East African urbanized regions.

In vitro and in vivo formation of 7-(2'-carboxyethyl)guanine from the liver carcinogen 1-nitroso-5,6-dihydrouracil and its reactions with water and methanol.

Base-catalyzed hydrolysis of the potent liver carcinogen 1-nitroso-5,6-dihydrouracil [(NDHU) CAS: 16813-36-8] afforded 3-hydroxypropionic acid and acrylic acid in 72 and 6% yield, respectively. The base-catalyzed methanolysis of NDHU gave quantitative yields of 3-methoxypropionic acid and methyl carbamate. These results indicate that base-catalyzed NDHU decomposition produces a 2-carboxyethyl carbonium-ion-type intermediate. When 3H-labeled NDHU was reacted at pH 8 with DNA and RNA, 7-(2'-carboxyethyl)guanine (CEG) was detected in the hydrolysate and was identified by its cochromatography with authentic CEG in five (for DNA) or three (for RNA) systems and by a reverse isotope-dilution procedure. Radioactively labeled CEG (identified as before) and five other labeled chromatographic fractions were present in liver DNA and RNA hydrolysates after [3H]NDHU was gavaged into MRC Wistar rats. These fractions persisted in the liver DNA for various times up to 33 days after the gavage. The CEG fraction was 94% of the radioactivity in DNA reacted in vitro, but it reached only 21% of the radioactivity in the liver DNA. The results are related to a study on single-strand breaks produced by NDHU in rat liver DNA.

Legacy and currently used pesticides in the atmospheric environment of Lake Victoria, East Africa.

The Lake Victoria watershed has extensive agricultural activity with a long history of pesticide use but there is limited information on historical use or on environmental levels. To address this data gap, high volume air samples were collected from two sites close to the northern shore of Lake Victoria; Kakira (KAK) and Entebbe (EBB). The samples, to be analyzed for pesticides, were collected over various periods between 1999 and 2004 inclusive (KAK 1999-2000, KAK 2003-2004, EBB 2003 and EBB 2004 sample sets) and from 2008 to 2010 inclusive (EBB 2008, EBB 2009 and EBB 2010 sample sets). The latter sample sets (which also included precipitation samples) were also analyzed for currently used pesticides (CUPs) including chlorpyrifos, chlorthalonil, metribuzin, trifluralin, malathion and dacthal. Chlorpyrifos was the predominant CUP in air samples with average concentrations of 93.5, 26.1 and 3.54 ng m(-3) for the EBB 2008, 2009, 2010 sample sets, respectively. Average concentrations of total endosulfan (ΣEndo), total DDT related compounds (ΣDDTs) and hexachlorocyclohexanes (ΣHCHs) ranged from 12.3-282, 22.8-130 and 3.72-81.8 pg m(-3), respectively, for all the sample sets. Atmospheric prevalence of residues of persistent organic pollutants (POPs) increased with fresh emissions of endosulfan, DDT and lindane. Hexachlorobenzene (HCB), pentachlorobenzene (PeCB) and dieldrin were also detected in air samples. Transformation products, pentachloroanisole, 3,4,5-trichloroveratrole and 3,4,5,6-tetrachloroveratrole, were also detected. The five most prevalent compounds in the precipitation samples were in the order chlorpyrifos>chlorothalonil>ΣEndo>ΣDDTs>ΣHCHs with average fluxes of 1123, 396, 130, 41.7 and 41.3 ng m(-2)sample(-1), respectively. PeCB exceeded HCB in precipitation samples. The reverse was true for air samples. Backward air trajectories suggested transboundary and local emission sources of the analytes. The results underscore the need for a concerted regional vigilance in management of chemicals.

Prediction of gene structure.

We have developed a hierarchical rule base system for identifying genes in DNA sequences. Atomic sites (such as initiation codons, stop codons, acceptor sites and donor sites) are identified by a number of different methods and evaluated by a set of filters and rules chosen to maximize sensitivity; these are combined into higher-order gene elements (such as exons), evaluated, filtered and combined as equivalence classes into probable genes, which are evaluated and ranked. The system has been tested on an extensive collection of vertebrate genes smaller than 15,000 bases. Results obtained show that, on average, 88% of the predicted coding region for a transcription unit is actually coding, and 80% of the actual coding is correctly predicted. This will, in most applications, be sufficient for a search against protein sequence databases for the identification of probable gene function. In addition, the system provides a general test platform for both gene atomic site identification and the rules for their evaluation and assembly.

Imprinted Rasgrf1 expression in neonatal mice affects olfactory learning and memory.

Rasgrf1 is genomically imprinted; only the paternally inherited allele is expressed in the neonatal mouse brain until weaning, at which time expression becomes biallelic. Whereas Rasgrf1 has been implicated in learning and memory via knockout studies in adult mice, the effect of its normal imprinted expression on these phenotypes has not yet been examined. Neonatal mice with experimentally manipulated patterns of imprinted Rasgrf1 expression were assessed on an associative olfactory task. Neonates lacking the normally expressed wild-type paternal allele exhibited significant impairment in olfactory associative memory. Adult animals in which neonatal imprinting had been manipulated were also behaviorally assessed; while neonatal imprinting significantly affects body weight even into adulthood, no learning and memory phenotype attributable to imprinting was observed in adults. Additional analyses of neonates showed imprinted Rasgrf1 transcript selective to olfactory bulb even in mice that were null for Rasgrf1 in the rest of the brain and showed that Rasgrf1 affects Ras and Rac activation in the brain. Taken together, these results indicate that Rasgrf1 expression from the wild-type paternal allele contributes to learning and memory in neonatal mice.

What evidence is there that the UK should tackle the potential emerging threat of methamphetamine toxicity rather than established recreational drugs such as MDMA ('ecstasy')?

BACKGROUND: There is increasing interest in whether methamphetamine is an emerging recreational drug in the UK. AIM: To determine what evidence is there that methamphetamine use is an emerging drug in the UK compared to established recreational drugs such as MDMA. DESIGN AND METHODS: We undertook a retrospective study collating data on the number of enquiries to both our poisons centre and the UK National Poisons Information Service (NPIS) relating to all recreational drugs, methamphetamine and MDMA; presentations to our Emergency Department (ED) with acute methamphetamine toxicity and the frequency of positive urine tests for methamphetamine and MDMA in workplace drug screening programmes. RESULTS: There was a small increase in the number of methamphetamine-related calls to our poisons centre, but it remained uncommon (0.1% of all recreational drugs cases in 2000 to 1.23% in 2006) compared to MDMA (17.3-42.7% of all recreational drugs cases). The number of 2005/6 enquiries to the UK NPIS for methamphetamine was 12, compared to 455 MDMA enquiries (0.014 and 0.52% of all enquiries, respectively). There were five presentations to our ED relating to methamphetamine over a 15-month period compared to 171 for MDMA. Of the 254 440 urine samples screened for the presence of drugs in the workplace (2000-06), three were positive for methamphetamine and 147 for MDMA. CONCLUSION: There is no evidence of increasing use of methamphetamine or that acute methamphetamine poisoning is a significant clinical problem compared to established recreational drugs such as MDMA. In our opinion, healthcare, educational and law enforcement resources should be proportionally directed towards tackling drugs that pose an immediate and continuing healthcare risk to the population rather than emerging recreational drugs.

Identification of the polyprotein termination site on encephalomyocarditis viral RNA.

We show by sequence analysis of a 420-base-long region adjacent to the 3' polyadenylic acid of encephalomyocarditis viral RNA and by carboxy terminus analysis of protein E that the termination site of encephalomyocarditis virus polyprotein translation consists of two successive UAG codons located at positions 121 to 126 from the 3' polyadenylic acid.

Safety evaluation of ritanserin--an investigational serotonin antagonist.

Ritanserin is an investigational serotonin-S2 receptor antagonist with activity in a variety of psychiatric disturbances characterized by dysthymia or anxiety. This investigation evaluates acute safety and tolerability of ritanserin in 12 healthy males. Ritanserin 10 mg, 20 mg, and placebo were administered as single doses in a randomized, double-blind, crossover fashion. Treatment effects on vital signs, laboratory tests, a mood evaluation test, electrocardiograms (ECGs), and reported adverse experiences were monitored. Plasma levels were determined at two hours postdose. Results indicated no clinically relevant effects on vital signs, laboratory tests, ECGs, or mood evaluations. Dose proportionality was demonstrated. The incidence of total adverse effects (primarily somnolence and fatigue) after single-dose administration was 25 percent for placebo, 75 percent for 10 mg, and 81.8 percent for 20 mg. There was a relationship between incidence of adverse effects and dose, but no general correlation between plasma levels and severity of adverse experiences. The results indicate that ritanserin is safe and tolerable following acute administration of 10 mg and 20 mg oral doses.

The nucleotide and deduced amino acid sequences of the encephalomyocarditis viral polyprotein coding region.

The nucleotide sequence of 7200 bases of encephalomyocarditis (EMC) viral RNA, including the complete polyprotein-coding region, was determined. The polyprotein is encoded within a unique translational reading frame, 6870 bases in length. Protein synthesis begins with the sequence Met-Ala-Thr, and ends with the sequence Leu-Phe-Trp, 126 bases from the 3' end of the RNA. Viral capsid and noncapsid proteins were aligned with the deduced amino acid sequence of the polyprotein. The proteolytic processing map follows the standard 4-3-4 picornaviral pattern except for a short leader peptide (8 kd), which precedes the capsid proteins. Identification of the proteolytic cleavage sites showed that EMC viral protease, p22, has cleavage specificity for gln-gly or gln-ser sequences with adjacent proline residues. The cleavage specificity of the host-coded protease(s) includes both tyr-pro and gln-gly sequences.