23 research outputs found

    A Hope for Heaven

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    Undergraduate 2-

    Utilizing vancomycin as secondary prophylaxis for the prevention of recurrent Clostridioides difficile infection

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    Background: Recurrent Clostridioides difficile infection (CDI) is associated with significant morbidity, mortality, and healthcare-related costs. Although data are minimal, agents including oral vancomycin have been used as secondary prophylaxis to prevent recurrent CDI. Methods: We conducted a randomized, double-blind, placebo-controlled trial to determine the effectiveness of vancomycin at preventing CDI from October 2019 to September 2022. Eligible patients had a history of at least 1 episode of CDI and were receiving systemic antibiotics for another condition. Participants were randomized 1:1 to oral vancomycin 125 mg by mouth twice daily and were interviewed at 1, 2, and 3 months thereafter to assess recurrence. We enrolled 26 patients: 15 completed the 1-month interview, 12 completed the 2-month interview, and 11 completed the full study. Those 15 participants who did not complete the 3-month interview were considered dropouts. The final sample for this study included those 11 participants who completed all interviews. Demographics and outcomes are shown in Table 1. Results: One case of recurrent CDI was reported at the 1-month interview and a second was reported at 3 months; both cases had received the placebo. The study was terminated early due to low enrollment. Conclusions: Although our results did not reach statistical significance and this study was limited in small sample size, our findings suggest that secondary prophylaxis with oral vancomycin may be beneficial in patients who are actively receiving antibiotics, which is consistent with prior retrospective studies. Future studies with larger sample sizes are still needed to examine this important question of whether secondary prophylaxis is useful for preventing recurrent CDI

    More men than women make mucosal IgA antibodies to Human papillomavirus type 16 (HPV-16) and HPV-18: a study of oral HPV and oral HPV antibodies in a normal healthy population

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    BACKGROUND: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. METHODS: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. RESULTS: Oral HPV infection was highest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09–12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97–6.2, P = 0.04). CONCLUSION: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation

    The characterisation and expression of HIV-1 subtype C gag

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    Thesis (MScMedSc) -- University of Stellenbosch, 2002.ENGLISH ABSTRACT: The gag gene of HIV-1 encodes for one of the major structural proteins, which contains several conserved cytotoxic T cell (CTL) epitopes. Gag specific CTL responses are important in controlling viral load during acute infection and asymptomatic stages of the infection. Currently, only one complete South African HIV-1 subtype C gag sequence has been published. The first aim of this study was to characterise the complete gag gene of 15 HIV-1 subtype C isolates, to be used as a set of reference sequences in the design of a South African HIV-1 subtype C vaccine. Fifteen HIV-1 subtype C isolates selected for this study, were isolated during 1998 and 1999 from the HIV-1 positive patients attending the Infectious Disease Clinic at Tygerberg Hospital. The gag gene of these isolates was amplified by PCR, cloned into mammalian expression vectors and sequenced. Restriction digest analyses as well as phylogenetic analyses were performed on the sequencing data. Previously published mutational analyses and CTL epitopes were compared to the predicted amino acid sequences of the gag clones. Sequences of 23 complete gag genes representing the 15 HIV-1 subtype C isolates as well as one complete sequence of an HIV-1 subtype B isolate were compiled. Subtyping by restriction fragment length polymorphism (RFLP) would have correctly identified 14 of the 15 subtype C isolates as subtype C and one as unidentifiable. The subtype B isolate would have also been correctly identified. Phylogenetic analyses showed that our subtype C isolates clustered with reference subtype C strains from various countries, including Botswana, India, Israel, Tanzania and Zambia. Strains from Ethiopia and Brazil formed a separate subtype C cluster. The diversity between our isolates was comparable to the diversity seen between all the HIV-1 subtype C strains. Comparisons of previously published mutational analyses and CTL epitopes to the predicted amino acid sequences of the gag clones, showed conservation in most of the clones throughout the sequence. A second aim was to establish transfection and Western Blot techniques in our laboratory for use in future studies. An in vitro transcription! translation assay was performed on the gag clones and the protein producing clones were used to transfect mammalian cells using electroporation. A Western blot was then used to screen for Gag protein expression in the transfected cell Iysates. The in vitro transcription! translation assay showed that seven of the 23 clones could produce a protein of -55 kDa in size. Four out of the seven of these clones gave a weak expression of a-55 kDa protein after transfection in a mammalian cell line. Since the completion of the experimental work of this study, other cloned HIV-1 genes have successfully been transfected into mammalian cells using the electroporation technique and the proteins produced were screened for by Western blot. To conclude with; the native form of the gag gene does not elicit strong expression of the protein, but studies have shown that expression can be improved by sequence-modification of the gag nucleotide sequence. Due to the conservation of gag, the sequence of any subtype C strain can be used for the development of a Southern African vaccine.AFRIKAANSE OPSOMMING: Die HIV-1 gag geen kodeer vir een van die hoof strukturele proterene en bevat verskeie sitotoksiese T-limfosiet epitope. Gag spesifieke sellulere immuun respons is belangrik vir die beheer van virale lading tydens akute infeksies en tydens asimptomatiese fases van die infeksie. Tans is slegs een volledige Suid Afrikaanse HIV-1 subtipe C nuklerensuur volgorde gepubliseer. Die eerste doel van hierdie studie was om die volledige gag geen van 15 HIV-1 subtipe C isolate te karakteriseer, om gebruik te word as In stel verwysings nukleiensuur volgordes, vir die ontwerp van In Suid Afrikaanse HIV-1 subtipe C entstof. Die 15 HIV-1 subtipe C isolate wat vir hierdie studie geselekteer is, is tydens 1998 en 1999 ge·lsoleer vanaf HIV-1 positiewe pasiente wat die Infeksiesiekte Kliniek, Tygerberg Hospitaal bygewoon het. Die gag geen van hierdie isolate is geamplifiseer deur PKR, gekloneer in soogdier ekspressie vektore en die nukleiensuur volgorde is bepaal. Die nuklerensuur volgorde is gebruik in restriksie ensiem analises asook filogenetiese analises. Reeds gepubliseerde mutasie analises en limfosiet epitope is met die voorspelde aminosuur volgorde van die gag klone vergelyk. Die nukleiensuur volgordes van die 23 volledige gag gene wat die 15 HIV-1 subtipe C isolate verteenwoordig, asook een volledige nukleiensuur volgorde van een HIV-1 subtipe B isolaat, is saamgestel. Subtipering deur middel van restriksie fragment lengte polimorfisme (RFLP) sou 14 uit die 15 subtipe C isolate korrek qerdentifiseer het, maar sou een nie kon identifiseer nie. RFLP sou ook die subtipe B isolaat korrek qerdentifiseer het. Filogenetiese analises het gewys dat ons subtipe C isolate met die verwysings subtipe C stamme van verskeie lande, insluitend Botswana, lndie, Israel, Tanzania en Zambie groepeer. Stamme van Ethiopie en Brasilie het In aparte subtipe C groep gevorm. Die diversiteit tussen ons isolate was vergelykbaar met die diversiteit tussen al die subtipe C stamme. Vergelykings van gepubliseerde mutasie analises en limfosiet epitope met die voorspelde aminosuur volgorde van die gag klone, het konservasie in meeste van die klone, deur die hele nukleiensuur volgorde, getoon. Die tweede doel was om die metodes van transfeksie en Westerse klad in ons laboratorium tot stand te bring. In vitro transkripsie/ translasie toetse is gedoen op die gag klone en die proteten produserende klone is gebruik om soogdierselle te transfekteer deur gebruik te maak van elektroporasie. In Westerse klad is toe gebruik om vir Gag proterenuitdrukkinq in die sellisate te toets. Die in vitro transkripsie/ translasie toets het getoon dat sewe uit 23 klone, In proteren van -55 kDa kon produseer. Vier uit die sewe van hierdie klone het In -55 kDa proteren swak uitgedruk na transfektering van soogdier selle. Sedert die voltooiing van die eksperimentele werk van hierdie stud ie, is ander gekloneerde HIV-1 gene suksesvol in soogdierselle getransfekteer met die gebruik van elektroporasie en die proterene is met In Westerse klad aangetoon. Ten slotte: die natuurlike vorm van die gag geen ontlok nie In sterk ekspressie van die proteren nie, maar ander studies het wei aangetoon dat die ekspressie verbeter kan word met modifikasie van die gag nukleiensuur volgorde. As gevolg van die konservasie van gag, kan die nuklerensuur volgorde van enige subtipe C stam gebruik word vir die ontwikkeling van In Suider Afrikaanse entstof.The Poliomyelitis Research FoundationThe South African AIDS Vaccine InitiativeHarry Crossley Foundatio

    Genetic analysis of the complete gag and env genes of HIV type 1 subtype C primary isolates from South Africa

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    South Africa has one of the fastest growing HIV-1 epidemics, with an estimated 4.7 million people infected. To better understand the genetic diversity of this epidemic and its potential impact on vaccine development, we have cloned and sequenced the complete gag and env genes of 13 primary virus isolates. Phylogenetic analysis of our sequences and 69 complete env genes from the Los Alamos and GenBank databases revealed multiple subclusters within subtype C. The V3 loop region was relatively conserved in all our strains when compared with other subtypes, but the region immediately downstream was highly variable. No intersubtype recombinant forms were observed when comparing the gag and env sequences. Characterization of the complete gag and env genes enabled us to select specific strains for further vaccine development.The publisher does not allow open access to the full text of this sequence note. If you however need access to the full text, please contact the Collection Administrator, or access the item via the e-journal collection.This work was supported by grants from the Poliomyelitis Research Foundation (PRF), the South African AIDS Vaccine Initiative (SAAVI), and the Harry Crossley Foundation. Excellent technical assistance from Brenda Robson and Annette Laten is acknowledged. We also thank Thomas J. Scriba and Florette K. Treurnicht for helpful discussions and critical reading of the manuscrip

    The Protective Effects of Neighborhood Collective Efficacy on British Children Growing Up in Deprivation: A Developmental Analysis

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    This article reports on the influence of neighborhood-level deprivation and collective efficacy on children’s antisocial behavior between the ages of 5 and 10 years. Latent growth curve modeling was applied to characterize the developmental course of antisocial behavior among children in the E-Risk Longitudinal Twin Study, an epidemiological cohort of 2,232 children. Children in deprived versus affluent neighborhoods had higher levels of antisocial behavior at school entry (24.1 vs. 20.5, p < .001) and a slower rate of decline from involvement in antisocial behavior between the ages of 5 and 10 (−0.54 vs. −0.78, p < .01). Neighborhood collective efficacy was negatively associated with levels of antisocial behavior at school entry (r =−.10, p < .01) but only in deprived neighborhoods; this relationship held after controlling for neighborhood problems and family-level factors. Collective efficacy did not predict the rate of change in antisocial behavior between the ages of 5 and 10. Findings suggest that neighborhood collective efficacy may have a protective effect on children living in deprived contexts
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