BackgroundFSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription.MethodsFSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection.ResultsOf 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1∶8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1∶8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1∶8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated.ConclusionsFactors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs.
Antimicrobial resistance of Listeria monocytogenes (n = 38) isolated from the four dairy farms to 15 antimicrobial agents was evaluated. All 38 L. monocytogenes isolates from the four farms evaluated were resistant to more than one antimicrobial in different combinations. All L. monocytogenes isolates evaluated were resistant to cephalosporin C (minimum inhibitory concentration [MIC] > or = 512 microg/mL), streptomycin (MIC > or = 32) and trimethoprim (MIC > or = 512). Most L. monocytogenes isolates were resistant to ampicillin (92%, MIC > or = 2), rifampicin (84%, MIC > or = 4), rifamycin (84%, MIC > or = 4), and florfenicol (66%, MIC > or = 32) and some were resistant to tetracycline (45%, MIC > or = 16), penicillin G (40%, MIC > or = 2) and chloramphenicol (32%, MIC > or = 32). All L. monocytogenes isolates were susceptible to amoxicillin, erythromycin, gentamicin, kanamycin and vancomycin. Susceptibility of L. monocytogenes to the antimicrobials evaluated was quite consistent among the dairy farms evaluated. However, some variability in antimicrobial susceptibility among dairy farms was noted. Nineteen of 38 L. monocytogenes isolates contained more than one antimicrobial resistance gene sequence. A high frequency of floR (66%) was found in L. monocytogenes followed by penA (37%), strA (34%), tetA (32%), and sulI (16%). Other tetracycline resistance genes (tetB, tetC, tetD, tetE, and tetG) and other antimicrobial resistance genes (cmlA, strB, aadA, sulI, vanA, vanB, ampC, ermB, ereA, and ereB) were not found in any of the L. monocytogenes isolates from the four dairy farms. Results of the present study demonstrated that L. monocytogenes isolated from the dairy farm environment were resistant to many antimicrobials and contained one or more antimicrobial resistance genes.
HIV prevalence is rising, especially among high risk females in Tijuana, Baja California, a Mexico-US border city situated on major migration and drug trafficking routes. We compared factors associated with HIV infection among male and female injection drug users (IDUs) in Tijuana in an effort to inform HIV prevention and treatment programs. IDUs aged ≥18 years were recruited using respondent-driven sampling and underwent testing for HIV, syphilis and structured interviews. Logistic regression identified correlates of HIV infection, stratified by gender. Among 1056 IDUs, most were Mexican-born but 67% were born outside Tijuana. Reasons for moving to Tijuana included deportation from the US (56% for males, 29% for females), and looking for work/better life (34% for females, 15% for males). HIV prevalence was higher in females versus males (10.2% vs. 3.5%, p = 0.001). Among females (N = 158), factors independently associated with higher HIV prevalence included younger age, lifetime syphilis infection and living in Tijuana for longer durations. Among males (N = 898), factors independently associated with higher HIV prevalence were syphilis titers consistent with active infection, being arrested for having ‘track-marks’, having larger numbers of recent injection partners and living in Tijuana for shorter durations. An interaction between gender and number of years lived in Tijuana regressed on HIV infection was significant (p = 0.03). Upon further analysis, deportation from the U.S. explained the association between shorter duration lived in Tijuana and HIV infection among males; odds of HIV infection were four-fold higher among male injectors deported from the US, compared to other males, adjusting for all other significant correlates (p = 0.002). Geographic mobility has a profound influence on Tijuana's evolving HIV epidemic, and its impact is significantly modified by gender. Future studies are needed to elucidate the context of mobility and HIV acquisition in this region, and whether US immigration policies adversely affect HIV risk.
GIV/Girdin, a nonreceptor GEF, directly links integrins to activation of trimeric G proteins to promote the acquisition of proinvasive traits in cancer cells.
Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation.
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