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71.

Objective

Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel.

Methods

Participants were randomized 1∶1:1∶1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively.

Results

Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms.

Conclusions

The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development.

Trial Registration

ClinicalTrials.gov NCT01232803.  相似文献   
72.

Background

MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs).

Materials and Methods

Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men.

Results

HIV-infected men showed 35–90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17–24% and 13–17% higher prevalence of lrHPVs (p-values ≤0.05). Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV-infected men.

Conclusions

HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV) viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are important prevention strategies for HPV infections that are relevant to anal cancer.  相似文献   
73.
74.
The orthocladiine Chironomidae genus Stictocladius Edwards was described originally from South America. Although recognised subsequently as present also in Australia and New Zealand, the true diversity in the Neotropics has remained unclear. After more than a decade of collections of both isolated adults and aquatic immature stages, we can recognise several new taxa and associate some immature stages. Thus, we describe Stictocladius prati n. sp. as male, female, pupa and larva; Stictocladius acutus n. sp. and Stictocladius acrilobus n. sp. as male, female and pupa; Stictocladius fimbriatus n. sp. as male and female; Stictocladius fovigus n. sp. and Stictocladius nudiventer n. sp. as male and pupa; and Stictocladius privicalcar n. sp. and Stictocladius prostatus n. sp. each as male imago alone. The male and female of Stictocladius pulchripennis Edwards is redescribed and the pupa described. The male and female of Stictocladius flavozonatus Edwards and the male of Stictocladius calonotum Edwards are described. Five pupal types are described: Stictocladius sp. A (near S. acrilobus), Stictocladius sp. B (possibly S. calonotum), Stictocladius sp. C (near S. calonotum), Stictocladius sp. D (possibly S. flavozonatus) and Stictocladius sp. E with uncertain affinity. A larva from Chile of the Stictocladius ??sofour type?? (Stictocladius sp. F) and an unreared larva from North America (Stictocladius sp. G) possibly belonging to S. acutus are described. Keys to named Neotropical male and female imagines of Stictocladius and to all pupal forms of Neotropical Stictocladius are provided. Some data concerning fourth instars of Stictocladius are presented. Means of differentiation from putative sister taxon Lopescladius are discussed.  相似文献   
75.
76.
M R Heath  PS Wright 《Gerodontology》1997,14(2):113-118
This essay complements that de Baat et al1 in the last issue with emphasis on the importance of the variability between individual older people. The consequent need for an open minded approach towards planning Prosthodontics is discussed, based on each patient's motivation for aesthetics, function, comfort and self esteem. Both functional expectations and motivation to learn effective health behaviour vary widely, and evaluation of both is essential for realistic planning because further tooth loss and the need for partial dentures occur so frequently. The consequent variation in plans raises the question – which are the strategic teeth to maintain a stable dental occlusion or a future tooth stabilised denture? For undergraduates this demands a non-rote approach to learning.  相似文献   
77.
78.
Abstract We examined broad scale patterns of diversity and distribution of lotic Chironomidae (Diptera) within the Wet Tropics bioregion of northern Queensland, Australia. Field surveys across broad latitudinal and altitudinal gradients within the Wet Tropics revealed a fauna of 87 species‐level taxa in 49 genera comprising three main elements: a small genuinely tropical fraction, and larger cosmopolitan and Gondwanan components. The latter group originated when Australia, as part of the ancient Gondwana supercontinent, was situated over Antarctic latitudes with a cooler, wetter climate than today. In the Wet Tropics, cool Gondwanan taxa occurred predominantly in upland and shaded lowland sites, but no species appeared narrowly temperature restricted, and there was no faunal zonation with altitude. Most chironomid species occurred at all latitudes within the Wet Tropics, with no evidence for an enduring effect of the historical rainforest contractions on current‐day distribution patterns. These findings contrast with those for aquatic faunas elsewhere in the world and for the terrestrial Wet Tropics fauna. We relate this to the generally broad environmental tolerances of Australian chironomids, and comment on why the latitudinal diversity gradient does not apply to the Australian chironomid fauna.  相似文献   
79.
Phylogenetic trees are a crucial backbone for a wide breadth of biological research spanning systematics, organismal biology, ecology, and medicine. In 2015, the Open Tree of Life project published a first draft of a comprehensive tree of life, summarizing digitally available taxonomic and phylogenetic knowledge. This paper reviews, investigates, and addresses the following questions as a follow‐up to that paper, from the perspective of researchers involved in building this summary of the tree of life: Is there a tree of life and should we reconstruct it? Is available data sufficient to reconstruct the tree of life? Do we have access to phylogenetic inferences in usable form? Can we combine different phylogenetic estimates across the tree of life? And finally, what is the future of understanding the tree of life?
  相似文献   
80.
As an archive of sequence data for over 165,000 species, GenBank is an indispensable resource for phylogenetic inference. Here we describe an informatics processing pipeline and online database, the PhyLoTA Browser (http://loco.biosci.arizona.edu/pb), which offers a view of GenBank tailored for molecular phylogenetics. The first release of the Browser is computed from 2.6 million sequences representing the taxonomically enriched subset of GenBank sequences for eukaryotes (excluding most genome survey sequences, ESTs, and other high-throughput data). In addition to summarizing sequence diversity and species diversity across nodes in the NCBI taxonomy, it reports 87,000 potentially phylogenetically informative clusters of homologous sequences, which can be viewed or downloaded, along with provisional alignments and coarse phylogenetic trees. At each node in the NCBI hierarchy, the user can display a "data availability matrix" of all available sequences for entries in a subtaxa-by-clusters matrix. This matrix provides a guidepost for subsequent assembly of multigene data sets or supertrees. The database allows for comparison of results from previous GenBank releases, highlighting recent additions of either sequences or taxa to GenBank and letting investigators track progress on data availability worldwide. Although the reported alignments and trees are extremely approximate, the database reports several statistics correlated with alignment quality to help users choose from alternative data sources.  相似文献   
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