Phase III Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection for Colon Cancer: An Intergroup Trial of the ECOG-ACRIN Cancer Research Group (E1292).

BACKGROUND: Studies suggest that adjuvant chemotherapy should be initiated at the earliest possible time. The Eastern Cooperative Oncology Group (ECOG) and Intergroup evaluated the effect of perioperative fluorouracil (5-FU) on overall survival (OS) for colon cancer. PATIENTS AND METHODS: This phase III trial randomized patients to receive continuous infusional 5-FU for 7 days starting within 24 h after curative resection (arm A) or no perioperative 5-FU (arm B). Patients with Dukes' B3 and C disease received adjuvant chemotherapy per standard of care. The primary endpoint of the trial was overall survival in patients with Dukes' B3 and C disease. The secondary objective was to determine whether a week of perioperative infusion would affect survival in patients with Dukes' B2 colon cancer with no additional chemotherapy. RESULTS: From August 1993 to May 2000, 859 patients were enrolled and 855 randomized (arm A: 427; arm B: 428). The trial was terminated early due to slow accrual. The median follow-up is 15.4 years (0.03-20.3 years). Among patients with Dukes' B3 and C disease, there was no statistically significant difference in OS [median 10.3 years (95% CI 8.4, 13.2) for perioperative chemotherapy and 9.3 years (95% CI 5.7, 12.3) for no perioperative therapy, one-sided log-rank p = 0.178, HR = 0.88 (95% CI 0.66, 1.16)] or disease-free survival (DFS). For patients with Dukes' B2 disease, there was also no significant difference in OS (median 16.1 versus 12.9 years) or DFS. There was no difference between treatment arms in operative complications. One week of continuous infusion of 5-FU was tolerable; 18% of arm A patients experienced grade 3 or greater toxicity.

Genomics of Population Differentiation in Humpback Dolphins, Sousa spp. in the Indo-Pacific Ocean.

Speciation is a fundamental process in evolution and crucial to the formation of biodiversity. It is a continuous and complex process, which can involve multiple interacting barriers leading to heterogeneous genomic landscapes with various peaks of divergence among populations. In this study, we used a population genomics approach to gain insights on the speciation process and to understand the population structure within the genus Sousa across its distribution in the Indo-Pacific region. We found 5 distinct clusters, corresponding to S. plumbea along the eastern African coast and the Arabian Sea, the Bangladesh population, S. chinensis off Thailand and S. sahulensis off Australian waters. We suggest that the high level of differentiation found, even across geographically close areas, is likely determined by different oceanographic features such as sea surface temperature and primary productivity.

Re-assessment of the Conservation Status of the Indo-Pacific Humpback Dolphin (Sousa chinensis) Using the IUCN Red List Criteria.

The IUCN Red List designation of the Indo-Pacific humpback dolphin (Sousa chinensis) is re-assessed in light of its newly recognized taxonomic status (it has recently been separated into three species) and findings that humpback dolphins along the coast of Bangladesh, and possibly eastern India, are phylogenetically distinct from other members of the Sousa genus. Sousa chinensis is found in Southeast/South Asia (in both the Indian and Pacific oceans), from at least the southeastern Bay of Bengal east to central China, and then south to the Indo-Malay Archipelago. There are no global population estimates, and the sum of available abundance estimates add up to about 5700 individuals, although only a portion of the range has been covered by surveys. This species occurs in shallow (<30m deep), coastal waters of the tropics and subtropics, and feeds mainly on small fishes. It has a similar reproductive biology to other large dolphins, occurs mostly in small groups, and generally has individual movements of about 50-200km(2). Major threats throughout the range include entanglement in fishing nets (primarily gillnets) and habitat destruction/degradation, although in some more industrialized areas, vessel traffic, and environmental contamination from organochlorines are also serious issues. Conservation management is largely lacking in most parts of the species' range, although there has been significant (though still inadequate) attention in some parts of China (e.g. Hong Kong and adjacent areas, and Taiwan). Much greater efforts are needed toward conservation of Indo-Pacific humpback dolphins to stop apparent declines, and to lower the species' extinction risk. Sousa chinensis meets the IUCN Red List requirements for Vulnerable (under criteria A4cd), with fisheries bycatch and habitat loss/degradation being the main pervasive threats.

The Reliability of Estimating Ki Values for Direct, Reversible Inhibition of Cytochrome P450 Enzymes from Corresponding IC50 Values: A Retrospective Analysis of 343 Experiments.

In the present study, we conducted a retrospective analysis of 343 in vitro experiments to ascertain whether observed (experimentally determined) values of Ki for reversible cytochrome P450 (P450) inhibition could be reliably predicted by dividing the corresponding IC50 values by two, based on the relationship (for competitive inhibition) in which Ki = IC50/2 when [S] (substrate concentration) = Km (Michaelis-Menten constant). Values of Ki and IC50 were determined under the following conditions: 1) the concentration of P450 marker substrate, [S], was equal to Km (for IC50 determinations) and spanned Km (for Ki determinations); 2) the substrate incubation time was short (5 minutes) to minimize metabolism-dependent inhibition and inhibitor depletion; and 3) the concentration of human liver microsomes was low (0.1 mg/ml or less) to maximize the unbound fraction of inhibitor. Under these conditions, predicted Ki values, based on IC50/2, correlated strongly with experimentally observed Ki determinations [r = 0.940; average fold error (AFE) = 1.10]. Of the 343 predicted Ki values, 316 (92%) were within a factor of 2 of the experimentally determined Ki values, and only one value fell outside a 3-fold range. In the case of noncompetitive inhibitors, Ki values predicted from IC50/2 values were overestimated by a factor of nearly 2 (AFE = 1.85; n = 13), which is to be expected because, for noncompetitive inhibition, Ki = IC50 (not IC50/2). The results suggest that, under appropriate experimental conditions with the substrate concentration equal to Km, values of Ki for direct, reversible inhibition can be reliably estimated from values of IC50/2.

TIM-3 regulates innate immune cells to induce fetomaternal tolerance.

TIM-3 is constitutively expressed on subsets of macrophages and dendritic cells. Its expression on other cells of the innate immune system and its role in fetomaternal tolerance has not yet been explored. In this study, we investigate the role of TIM-3-expressing innate immune cells in the regulation of tolerance at the fetomaternal interface (FMI) using an allogeneic mouse model of pregnancy. Blockade of TIM-3 results in accumulation of inflammatory granulocytes and macrophages at the uteroplacental interface and upregulation of proinflammatory cytokines. Furthermore, TIM-3 blockade inhibits the phagocytic potential of uterine macrophages resulting in a build up of apoptotic bodies at the uteroplacental interface that elicits a local immune response. In response to inflammatory cytokines, Ly-6C(hi)G(neg) monocytic myeloid-derived suppressor cells expressing inducible NO synthase and arginase 1 are induced. However, these suppressive cells fail to downregulate the inflammatory cascade induced by inflammatory granulocytes (Ly-6C(int)G(hi)) and apoptotic cells; the increased production of IFN-γ and TNF-α by inflammatory granulocytes leads to abrogation of tolerance at the FMI and fetal rejection. These data highlight the interplay between cells of the innate immune system at the FMI and their influence on successful pregnancy in mice.

In vitro inhibition of human liver cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes by rose bengal: system-dependent effects on inhibitory potential.

1. Rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is being developed for the treatment of cutaneous melanoma and hepatocellular carcinoma. Interestingly, rose bengal can generate singlet oxygen species upon exposure to light. 2. We evaluated rose bengal as an in vitro inhibitor of cytochrome P450 (CYP) or UDP-glucuronosyltransferase (UGT) enzymes in both human liver microsomes (HLM) and cryopreserved human hepatocytes (CHHs) under both yellow light and dark conditions. 3. Rose bengal directly inhibited CYP3A4/5 and UGT1A6 in HLM under yellow light with inhibitor concentration that causes 50% inhibition (IC50) values of 0.072 and 0.035 µM, respectively; whereas much less inhibition was observed in the dark with the IC50 values increasing 43- and 120-fold, respectively. To determine if a more physiologically-relevant test system could be protected from such an effect, rose bengal was evaluated as an inhibitor of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4/5 and UGT enzymes in CHH. All IC50 values were similar (64 ± 8 µM) and little to no effect of light on inhibitory potential was observed. 4. Given the IC50 values in CHH increased an order of magnitude compared to HLM and the atypical pharmacokinetics of the drug, the risk of rose bengal to cause clinically relevant drug-drug interactions is likely low, particularly when administered to cancer patients on an intermittent schedule.

Stable isotope tracer to determine uptake and efflux dynamics of ZnO Nano- and bulk particles and dissolved Zn to an estuarine snail.

Zinc oxide nanoparticles (ZnO NPs) are among the most commercialized engineered nanomaterials. Their biological impact in aquatic organisms has been associated with dissolution, but there is also evidence of nanospecific effects. In this study the waterborne uptake and efflux kinetics of isotopically labeled (68)ZnO NPs (7.8 ± 1.2 nm), in comparison to aqueous (68)Zn and (68)ZnO bulk particles (up to 2 µm), were determined for the estuarine snail Peringia ulvae following a 7 d exposure (nominally 20 µg (68)Zn L(-1)) and 28 d depuration. Detection of the (68)Zn label was achieved by high precision multiple-collector ICP-MS (MC-ICP-MS). Previous characterization in artificial estuarine water revealed that the NPs underwent initial aggregation and solubilized up to 60% within 1-2 days. Bulk and aqueous forms were significantly more bioavailable than (68)ZnO NPs (p < 0.05), but after correcting for dissolution, aqueous (0.074 L(-1) g(-1) d(-1)) and NP (0.070 L(-1) g(-1) d(-1)) uptake rate constants were highly comparable. The rate constant of loss for (68)Zn aqueous (0.012 ± 0.005 d(-1)) and (68)ZnO NPs (0.012 ± 0.007 d(-1)) were identical. These results strongly suggest that in this exposure scenario the bioaccumulation of Zn from ZnO NPs is primarily dependent upon solubility.

Population differentiation of 2 forms of Bryde's whales in the Indian and Pacific Oceans.

Accurate identification of units for conservation is particularly challenging for marine species as obvious barriers to gene flow are generally lacking. Bryde's whales (Balaenoptera spp.) are subject to multiple human-mediated stressors, including fisheries bycatch, ship strikes, and scientific whaling by Japan. For effective management, a clear understanding of how populations of each Bryde's whale species/subspecies are genetically structured across their range is required. We conducted a population-level analysis of mtDNA control region sequences with 56 new samples from Oman, Maldives, and Bangladesh, plus published sequences from off Java and the Northwest Pacific. Nine diagnostic characters in the mitochondrial control region and a maximum parsimony phylogenetic analysis identified 2 genetically recognized subspecies of Bryde's whale: the larger, offshore form, Balaenoptera edeni brydei, and the smaller, coastal form, Balaenoptera edeni edeni. Genetic diversity and differentiation indices, combined with a reconstructed maximum parsimony haplotype network, indicate strong differences in the genetic diversity and population structure within each subspecies. Discrete population units are identified for B. e. brydei in the Maldives, Java, and the Northwest Pacific and for B. e. edeni between the Northern Indian Ocean (Oman and Bangladesh) and the coastal waters of Japan.

Macrolitter and mesolitter in the Thames Estuary: A temporal litter assessment and brand audit of submerged and riverbed debris.

Macroplastic is a growing concern for marine environments with estuaries providing a major pathway for pollution from land-based sources to the sea. In the Thames Estuary, plastic was abundant floating below the surface and on the riverbed, with an average catch per unit effort of 0.57 ± 0.42 and 2.75 ± 2.44 item per minute respectively. Whilst the abundance of litter differed between midwater and benthic zones, the types of products recovered did not. These were identified through visual examination and use of a unique citizen science engagement protocol, allowing for the item age, brand and countries of origin to be established. The majority of litter from the present study (n = 1335) was packaging (40%), some of which was over 30-years old and may have originated from landfill run off. Also abundant was sewage-related debris, the inputs of which was related to heavy or prolonged rainfall. Peaks in this material were recorded in September 2020 following the greatest volume of rain recorded in a single day and in June 2019 after the longest period of continuous rainfall. The Covid-19 pandemic did not influence the abundance or diversity of plastic recovered between December 2018 and September 2020. The durability of plastic ensures it has high potential for harm through entanglement, deoxygenation of sediment and ingestion. The retention in the environment also increases opportunities to fragment into micro- or nanoplastics and, therefore, it is important to monitor plastics at both a macro- and micro-scale.

Social network and other correlates of HIV testing: findings from male sex workers and other MSM in Shanghai, China.

Although the Chinese government provides free-of-charge voluntary HIV counseling and testing, HIV testing rates among men who have sex with men (MSM) are reported to be extremely low. This study examines the association of structural and psychosocial factors and social network characteristics with HIV testing behaviors among "money boys" and general MSM in Shanghai. Overall, 28.5% of "money boys" and 50.5% of general MSM had never tested for HIV despite high rates of reported HIV risk behaviors. Factors associated with not testing for HIV included: not knowing of a testing site, limited HIV knowledge, low perceived HIV risk, concern about HIV testing confidentiality, being a closeted gay, not using the Internet, and having a small social network or network with few members who had tested for HIV. Future efforts to promote HIV testing should focus on outreach to general MSM, confidentiality protection, decreasing the stigma of homosexuality, and encouraging peer education and support through the Internet and social networks.

Bioaccumulation dynamics and modeling in an estuarine invertebrate following aqueous exposure to nanosized and dissolved silver.

Predicting the environmental impact of engineered nanomaterials (ENMs) is increasingly important owing to the prevalence of emerging nanotechnologies. We derived waterborne uptake and efflux rate constants for the estuarine snail, Peringia ulvae, exposed to dissolved Ag (AgNO(3)) and silver nanoparticles (Ag NPs), using biodynamic modeling. Uptake rates demonstrated that dissolved Ag is twice as bioavailable as Ag in nanoparticle form. Biphasic loss dynamics revealed the faster elimination of Ag from Ag NPs at the start of depuration, but similar slow efflux rate constants. The integration of biodynamic parameters into our model accurately predicted Ag tissue burdens during chronic exposure with 85% of predicted values within a factor of 2 of observed values. Zeta potentials for the Ag NPs were lower in estuarine waters than in waters of less salinity; and uptake rates in P. ulvae were slower than reported for the freshwater snail Lymnaea stagnalis in similar experiments. This suggests aggregation of Ag NPs occurs in estuarine waters and reduces, but does not eliminate, bioavailability of Ag from the Ag NPs. Biodynamic modeling provides an effective methodology to determine bioavailable metal concentrations (originating from metal and metal-oxide nanoparticles) in the environment and may aid future ENM risk assessment.

Safeguarding human-wildlife cooperation.

Human-wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human-honeyguide and human-dolphin cooperation, but these are at risk of joining several inactive forms (including human-wolf and human-orca cooperation). Human-wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components-a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge-which face threats from ecological and cultural changes. To safeguard human-wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures. Please see AfricanHoneyguides.com/abstract-translations for Kiswahili and Portuguese translations of the abstract.

Development and implementation of a collaborative, multistakeholder research and practice model on HIV prevention targeting Asian/Pacific Islander men in the United States who have sex with men.

We describe lessons learned from a national HIV prevention research program grounded in community-based participatory research, the Men of Asia Testing for HIV (MATH) Study, which targeted self-identified Asian/Pacific Islander men in the United States who have sex with men. We discuss the genesis of and impetus for the study and then describe its various facets, including accomplishments, challenges, and unanticipated consequences. We conclude with a discussion about the real-world practice of community-based participatory research with respect to the MATH Study in particular and similar research in general.

Cellular internalization of silver nanoparticles in gut epithelia of the estuarine polychaete Nereis diversicolor.

Silver nanoparticles (AgNPs) are widely used which may result in environmental impacts, notably within aquatic ecosystems. As estuarine sediments are sinks for numerous pollutants, but also habitat and food for deposit feeders such as Nereis diversicolor, ingested sediments must be investigated as an important route of uptake for NPs. N. diversicolor were fed sediment spiked with either citrate capped AgNPs (30 ± 5 nm) or aqueous Ag for 10 days. Postexposure AgNPs were observed in the lumen of exposed animals, and three lines of evidence indicated direct internalization of AgNPs into the gut epithelium. With TEM, electron-dense particles resembling AgNPs were observed associated with the apical plasma membrane, in endocytotic pits and in endosomes. Energy dispersive X-ray analysis (EDX) confirmed the presence of Ag in these particles, which were absent in controls. Subcellular fractionation revealed that Ag accumulated from AgNPs was predominantly associated with inorganic granules, organelles, and the heat denatured proteins; whereas dissolved Ag was localized to the metallothionein fraction. Collectively, these results indicate separate routes of cellular internalization and differing in vivo fates of Ag delivered in dissolved and NP form. For AgNPs an endocytotic pathway appears to be a key route of cellular uptake.

Accumulation of trace metals in freshwater macroinvertebrates across metal contamination gradients.

Historical mining activities cause widespread, long-term trace metal contamination of freshwater ecosystems. However, measuring trace metal bioavailability has proven difficult, because it depends on many factors, not least concentrations in water, sediment and habitat. Simple tools are needed to assess bioavailabilities. The use of biomonitors has been widely advocated to provide a realistic measure. To date there have been few attempts to identify ubiquitous patterns of trace metal accumulation within and between freshwater biomonitors at geographical scales relevant to trace metal contamination. Here we address this through a nationwide collection of freshwater biomonitors (species of Gammarus, Leuctra, Baetis, Rhyacophila, Hydropsyche) from 99 English and Welsh stream sites spanning a gradient of high to low trace metal loading. The study tested for inter-biomonitor variation in trace metal body burden, and for congruence amongst accumulations of trace metals within taxa and between taxa across the gradient. In general, significant differences in trace metal body burden occurred between taxa: Gammarus sp. was the most different compared with insect biomonitors. Bivariate relationships between trace metals within biomonitors reflected trace metal profiles in the environment. Strong correlations between some trace metals suggested accumulation was also influenced by physiological pathways. Bivariate relationships between insect biomonitors for body burdens of As, Cu, Mn and Pb were highly consistent. Our data show that irrespective of taxonomic or ecological differences, there is a commonality of response amongst insect taxa, indicating one or more could provide consistent measures of trace metal bioavailability.

London's river of plastic: High levels of microplastics in the Thames water column.

This opportunistic study focussed on the quantification of microplastics in the River Thames water column, the catchment responsible for draining Greater London. Two sites on the tidal Thames were sampled; one upstream of the City of London at Putney, and the other downstream at Greenwich. Water column samples were collected from June through to October 2017, being taken on the ebb and flood tides, at the surface and a depth of 2 m. Microplastics (excluding microfibres) were identified to test whether the load varied between the two sites in relation to tide, depth and season. Secondary microplastics, films and fragments, contributed 93.5% of all those found at Putney and Greenwich. Site, tide, depth and month affected density, with the combined interaction of month and site found to have the greatest influence on microplastics. Fourier Transform Infrared Spectroscopy analysis showed that polyethylene and polypropylene were the most common polymers collected from the River, suggesting broken down packaging was the primary source of microplastics in these samples. Excluding microfibres, the estimate of microplastics in the water column was 24.8 per m3 at Putney and 14.2 per m3 at Greenwich. These levels are comparable to some of the highest recorded in the world.

High prevalence of plastic ingestion by Eriocheir sinensis and Carcinus maenas (Crustacea: Decapoda: Brachyura) in the Thames Estuary.

This study presents evidence for microplastic contamination in two resident species of brachyuran crab from the Thames Estuary: the native shore crab, Carcinus maenas (Linneaus, 1758) and the invasive Chinese mitten crab, Eriocheir sinensis (H. Milne Edwards, 1853). The gills, gastric mill and intestine of 94 C. maenas and 41 E. sinensis were examined. Crabs were sampled periodically (ca. every three months) between December 2018 and October 2019. A total of 874 plastics were recovered, ranging 34 µm-34 mm in length. Overall, 71.3% and 100% of C. maenas and E. sinensis, respectively, contained at least one item (fibre, film, fragment or tangle of fibres) in the gill chamber, gastric mill or gastrointestinal tract. The most common items were fibres (78.5%) but in some cases, particularly in the gastric mill, these were aggregated into tangles (7.8%). Almost all E. sinensis contained tangles of fibres (95.1%), whereas, relatively few C. maenas contained similar tangles (10.6%).

Maculopathy in Patients with Monoclonal Gammopathy of Undetermined Significance.

PURPOSE: To describe clinical findings, laboratory values, and treatment response of patients with monoclonal gammopathy of undetermined significance (MGUS) demonstrating neurosensory macular detachment. DESIGN: Retrospective case series. PARTICIPANTS: Seven eyes of 4 patients (3 men and 1 woman; age range, 60-81 years) with neurosensory macular detachment, treatment-resistant submacular fluid, and vitelliform material. METHODS: We retrospectively reviewed the medical and ocular histories, ocular examination findings, retinal imaging, ocular disease course, and laboratory findings in 4 patients with submacular fluid associated with MGUS. MAIN OUTCOME MEASURES: Description of the macular findings and treatment courses of 4 patients diagnosed with MGUS maculopathy. RESULTS: Seven eyes of 4 patients demonstrated neurosensory macular detachment with treatment-resistant submacular fluid and vitelliform material. No eyes demonstrated signs of significant hyperviscosity retinopathy. Fluorescein angiography showed no definite leakage in any involved eye. Laboratory evaluation revealed immunoglobulin G MGUS in all 4 patients. All 4 patients were resistant to treatments aimed at resolving the subretinal fluid, including some combination of anti-vascular endothelial growth factor injections, photodynamic therapy, topical dorzolamide, oral dosing of eplerenone or acetazolamide, or some combination thereof. In 3 patients, MGUS underwent malignant transformation 24 to 144 months after diagnosis, in 1 patient to lymphoplasmacytic lymphoma and in 2 patients to multiple myeloma. The fourth patient showed no evidence of malignancy 8 years after diagnosis. CONCLUSIONS: Submacular fluid without fluorescein leakage and unresponsive to conventional treatment may suggest an underlying immunoproliferative disorder that we have termed monoclonal gammopathy of macular significance. Given the propensity for monoclonal gammopathy of macular significance to transform into malignant disease in our series, serum protein analysis should be considered in patients with neurosensory macular detachment not attributable to known causes.

Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes.

Cytochrome P450s (P450s) metabolize a large number of diverse substrates with specific regio- and stereospecificity. A number of compounds, including nicotine, cotinine, and aflatoxin B(1), are metabolites of the 94% identical CYP2A13 and CYP2A6 enzymes but at different rates. Phenacetin and 4-aminobiphenyl were identified as substrates of human cytochromes P450 1A2 and 2A13 but not of CYP2A6. The purpose of this study was to identify active site amino acids that are responsible for CYP2A substrate specificity using phenacetin as a structural probe. Ten amino acid residues that differ in the CYP2A13 and CYP2A6 active sites were exchanged between the two enzymes. Phenacetin binding revealed that the six substitution, CYP2A13 S208I, A213S, F300I, A301G, M365V, and G369S decreased phenacetin affinity. Although incorporation of individual CYP2A13 residues into CYP2A6 had little effect on this enzyme's very low levels of phenacetin metabolism, the combination of double, triple, and quadruple substitutions at positions 208, 300, 301, and 369 increasingly endowed CYP2A6 with the ability to metabolize phenacetin. Enzyme kinetics revealed that the CYP2A6 I208S/I300F/G301A/S369G mutant protein O-deethylated phenacetin with a K(m) of 10.3 muM and a k(cat) of 2.9 min(-1), which compare very favorably with those of CYP2A13 (K(m) of 10.7 muM and k(cat) of 3.8 min(-1)). A 2.15 A crystal structure of the mutant CYP2A6 I208S/I300F/G301A/S369G protein with phenacetin in the active site provided a structural rationale for the differences in phenacetin metabolism between CYP2A6 and CYP2A13.

Gender differences in intimate partner violence on substance abuse, sexual risks, and depression among a sample of South Africans in Cape Town, South Africa.

Because men account for nearly half of the HIV cases in South Africa, it is critical to understand the contexts in which they live and the behaviors in which they engage. The purpose of this study was to describe and examine gender differences in intimate partner violence on substance abuse, sexual risks, and depression among a sample of South Africans in Cape Town. We found that recent exposure to intimate partner violence among men was associated with all forms of drug use, whereas women who were recently abused were more likely to suffer from depression and problem drinking. We also found high levels of problem drinking among both men (58%) and women (42%). Men were more likely to use drugs. Exposure to community violence increased sexual risk behaviors among men. Overall, these gender differences have important implications for alcohol and drug prevention strategies as they relate to HIV transmission risk.