Delivery mode impacts gut bacteriophage colonization during infancy.

Background: Cesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory and immune health outcomes. Although gut bacteriophages can alter gut microbiome composition and impact host immune responses, little is known about how delivery mode impacts bacteriophage colonization over time. To begin to address this we examined how delivery mode affected bacteriophage colonization over the first two years of life.

An Untargeted Approach for Revealing Electrophilic Metabolites.

Reactive electrophilic intermediates such as coenzyme A esters play central roles in metabolism but are difficult to detect with conventional strategies. Here, we introduce hydroxylamine-based stable isotope labeling to convert reactive electrophilic intermediates into stable derivatives that are easily detectable LC-MS. In the model system , parallel treatment with NHOH and NHOH revealed >1000 labeled metabolites, e.

Facing famine: Somali experiences in the famine of 2011.

In 2011-12, Somalia experienced the worst famine of the twenty- first century. Since then, research on the famine has focused almost exclusively on the external response, the reasons for the delay in the international response, and the implications for international humanitarian action in the context of the "global war on terror." This paper focuses on the internal, Somali response to the famine.

An ENU-induced mouse mutant of SHIP1 reveals a critical role of the stem cell isoform for suppression of macrophage activation.

In a recessive ENU mutagenesis screen for embryonic lethality, we identified a mouse pedigree with a missense mutation of SHIP1 (SHIP1(el20)) leading to an amino acid substitution I641T in the inositol-5'-phosphatase domain that represses phosphatidylinositol-3-kinase signaling. Despite detectable expression of functional SHIP1 protein, the phenotype of homozygous SHIP1(el20/el20) mice was more severe than gene-targeted SHIP1-null (SHIP1(-/-)) mice. Compared with age-matched SHIP1(-/-) mice, 5-week-old SHIP1(el20/el20) mice had increased myeloid cells, serum IL-6 levels, marked reductions in lymphoid cells, and died by 7 weeks of age with infiltration of the lungs by activated macrophages.

An experimental hut evaluation of Olyset nets against anopheline mosquitoes after seven years use in Tanzanian villages.

Background: Long-lasting insecticidal nets (LLINs) are advocated by WHO for protection against malaria. Of the three brands of LLINs currently approved by WHO, Olyset(R) is the only one currently granted full recommendation. With this type of LLIN, the insecticide (permethrin) is incorporated into the polyethylene fibre during manufacture and diffuses from the core to the surface, thereby maintaining surface concentrations.

Insecticide-treated bed-nets for malaria mosquito control.

Pyrethroid-treated bed-nets act against late-night biting mosquitoes, like traps baited by the body odor of the occupant. The personal protective effect of treated nets is considerable, even if they are torn. However, some biting of the occupants does occur, as shown by matching microsatellite alleles in mosquito blood meals to those of net occupants.

Comparison of coverage with insecticide-treated nets in a Tanzanian town and villages where nets and insecticide are either marketed or provided free of charge.

Background: There is much emphasis on social marketing as a means of scaling up coverage with insecticide-treated nets and the question has arisen whether nets provided free-of-charge will be looked after by householders.

Methods: Over several years questionnaires and surveys of usage and condition of nets were carried out throughout a town and 15 villages in north-east Tanzania, where nets and insecticide have to be purchased and in 24 other villages where over 15000 nets had been donated and annual re-treatment is provided free-of-charge.

Results: There was very high population coverage in the town but, in the villages where nets have to be purchased, only 9.

Tests of Olyset nets by bioassay and in experimental huts.

Background: Olyset nets are a type of long-lasting insecticidal net made of polyethylene fibre with permethrin incorporated into it and with a 4 mm mesh size.

Bioassays: Olyset netting was wrapped around a wire frame and the mosquitoes were released inside for bioassays. There was significantly faster knockdown and higher percent mortality than bioassays with the netting attached to a WHO cone with a piece of cardboard on the other side of the net to prevent escapes through the large mesh.

Functional similarities between phage lambda Orf and Escherichia coli RecFOR in initiation of genetic exchange.

Genetic recombination in bacteriophage lambda relies on DNA end processing by Exo to expose 3'-tailed strands for annealing and exchange by beta protein. Phage lambda encodes an additional recombinase, Orf, which participates in the early stages of recombination by supplying a function equivalent to the Escherichia coli RecFOR complex. These host enzymes assist loading of the RecA strand exchange protein onto ssDNA coated with ssDNA-binding protein.

Multi-country field trials comparing wash-resistance of PermaNet and conventional insecticide-treated nets against anopheline and culicine mosquitoes.

Insecticide-treated bednets (ITNs) are commonly used as a means of personal protection from malaria transmission by anopheline mosquitoes (Diptera: Culicidae). Long-lasting insecticidal nets (LLINs) have special treatments intended to remain effective after many washes. The present trials assessed the efficacy and wash-resistance of several production batches of PermaNet (polyester net coated with polymer resin containing pyrethroid insecticide deltamethrin 55 mg ai/m2) against malaria vectors in Pakistan, Iran and Tanzania compared to ITNs conventionally treated with alphacypermethrin 15 or 20 mg ai/m2, or deltamethrin 25 or 50 mg ai/m2.

Measuring the efficacy of insecticide treated bednets: the use of DNA fingerprinting to increase the accuracy of personal protection estimates in Tanzania.

Summary Insecticide-treated nets have proved successful in the prevention of malaria as a result of both the personal protection with which they provide the sleeper and also the 'mass effect' on the local mosquito population when they are used on a community-wide basis. Personal protection estimates are normally based on comparisons of the numbers of bloodfed mosquitoes found in rooms with and without nets, however it seemed possible that a number of those mosquitoes may not have fed on the occupants of the rooms in which they were found but had entered after feeding elsewhere. To address this possible source of error, we used an 8-locus microsatellite system to identify the source of bloodmeals of Anopheles gambiaes.

Insecticide treated nets: impact on vector populations and relevance of initial intensity of transmission and pyrethroid resistance.

Insecticide treated bednets locate a deposit of a quick-acting insecticide of low human toxicity between a sleeper and host-seeking mosquitoes. Thus a chemical barrier is added to the often incomplete physical barrier provided by the net. Treated nets may be considered as mosquito traps baited by the odour of the sleeper.

Variation of malaria transmission and morbidity with altitude in Tanzania and with introduction of alphacypermethrin treated nets.

Background: Highland areas with naturally less intense malaria transmission may provide models of how lowland areas might become if transmission was permanently reduced by sustained vector control. It has been argued that vector control should not be attempted in areas of intense transmission.

Methods: Mosquitoes were sampled with light traps, pyrethrum spray and window exit traps.

Scaling-up coverage with insecticide-treated nets against malaria in Africa: who should pay?

Insecticide-treated nets (ITNs) have been shown to reduce the burden of malaria in African villages by providing personal protection and, if coverage of a community is comprehensive, by reducing the infective mosquito population. We do not accept the view that scaling-up this method should be by making villagers pay for nets and insecticide, with subsidies limited so as not to discourage the private sector. We consider that ITNs should be viewed as a public good, like vaccines, and should be provided via the public sector with generous assistance from donors.

Use of floating layers of polystyrene beads to control populations of the filaria vector Culex quinquefasciatus.

Floating layers of polystyrene beads suffocate mosquito larvae and pupae and inhibit egg laying. The layers are very durable in breeding sites with water contained within walls, as in wet pit latrines and soakage pits. In some areas such pits constitute an important breeding site for Culex quinquefasciatus.

Pyrethroid resistance in tropical bedbugs, Cimex hemipterus, associated with use of treated bednets.

When Tanzanian villages were provided with pyrethroid-treated bednets, bedbugs (Cimicidae) disappeared; however, after about 6 years they have re-appeared in these villages. Using a newly devised test-kit, susceptibility tests of bedbugs Cimex hemipterus (Fabricius) from five of these villages showed that there is resistance to permethrin and alphacypermethrin in bedbugs from each of the villages, in contrast to those from five villages without treated nets. Circumstantial evidence indicates that bedbug resistance to pyrethroid insecticides may evolve more readily in villages with incomplete coverage rates of treated bednets, allowing bedbug infestations to become re-established.

Effect of community-wide use of insecticide-treated nets for 3-4 years on malarial morbidity in Tanzania.

Objectives: To investigate (1) benefits due to personal protection of individual net users vs. mass killing of mosquitoes within villages as a result of widespread net usage; (2) sustainability over several years of benefits against malarial morbidity of insecticide-treated nets; (3) distribution of the benefits in different age groups of children and (4) whether, as a result of fading immunity, older age groups 'paid for' the benefits which they had enjoyed when younger.

Methods: (1) Tabulation of earlier data to compare personal and community-wide effects against mosquito vectors; (2) two cross-sectional surveys for malaria parasitaemia, malarial fever, anaemia and splenomegaly in children in eight Tanzanian villages, in which there had been community-wide use of bednets which had been annually re-treated with alphacypermethrin for 3-4 years; (3) comparison between children of different age groups and with intact, torn or no nets in these villages and in 4-6 villages without nets.

Mutations in dhfr in Plasmodium falciparum infections selected by chlorproguanil-dapsone treatment.

Treatment with the novel antifolate drug combination chlorproguanil-dapsone effectively cleared asymptomatic Plasmodium falciparum infections in 246 (93.5%) of 263 children in the Usambara Mountains of Tanzania during the course of a 2-week follow-up. Samples from 71 recurrent infections, collected over a 9-week follow-up, showed selection for parasites with the triple mutant Ile(51)-Arg(59)-Asn(108) in dihydrofolate reductase.

aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation.

Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin.

Insecticide-treated bed nets reduce plasma antibody levels and limit the repertoire of antibodies to Plasmodium falciparum variant surface antigens.

The use of insecticide-treated bed nets (ITN) has been documented to reduce malaria morbidity and mortality in areas with endemic malaria, but concerns have been raised that ITN usage could affect the acquisition of malaria immunity. Several lines of evidence have indicated that antibodies against variant surface antigens (VSA) are important in the development of naturally acquired immunity to Plasmodium falciparum malaria and may thus be good indicators of immune status. We have compared the levels of VSA antibodies in plasma from children who have used ITN for 4 years to levels in plasma from children from a nearby village not using ITN.

A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.

Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been reported in Plasmodium falciparum in north-eastern Tanzania, and the identification of a suitable antimalarial to replace SP is now a high priority. We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic falciparum infection. A total of 220 children with parasitaemia > or = 2000 per microL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.