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1.
Gynecol Oncol ; 152(3): 465-471, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30876490

RESUMO

OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.


Assuntos
Erradicação de Doenças/métodos , Modelos Teóricos , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Austrália , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Erradicação de Doenças/normas , Detecção Precoce de Câncer , Feminino , Política de Saúde , Humanos , Modelos Biológicos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/virologia , Adulto Jovem
2.
Am J Reprod Immunol ; 80(4): e13029, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30076667

RESUMO

PROBLEM: In women, the use of progestin-based contraception may increase the risk of vaginal HIV acquisition. We previously showed in macaques that there is a significantly higher simian-human immunodeficiency virus (SHIV) acquisition rate in the luteal phase of the menstrual cycle, which presents a naturally high-progesterone state, and this may be attributable to altered expression of innate immune factors. We hypothesized that progestin-based contraception, especially depot medroxyprogesterone acetate (DMPA), would, in a similar way, affect mucosal immune factors that influence HIV acquisition risk. METHOD OF STUDY: We used a pig-tailed macaque model to evaluate the effects of two progestin-based contraceptives, DMPA, and levonorgestrel (LNG)/ethinyl estradiol (EE)-based combined oral contraceptives (COCs), on innate mucosal factors. We compared the vaginal epithelial thickness data from previous studies and used cytokine profiling and microarray analysis to evaluate contraception-induced molecular changes in the vagina. RESULTS: The administration of DMPA caused a reduction in the thickness of the vaginal epithelium relative to that of the follicular or luteal phase. DMPA also induced a significant increase in vaginal levels of the anti-inflammatory cytokine IL-10. Both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, including widespread downregulation of antiviral genes. CONCLUSION: The use of progestin-based contraception might engender a milieu that poses an increased risk of HIV acquisition as compared to both the luteal and follicular phases of the menstrual cycle.

3.
Hip Int ; : 1120700018775317, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29808720

RESUMO

INTRODUCTION: The Oxford Hip Score (OHS) is a commonly used patient-reported outcome measure (PROM), comprising 12 questions. We present the incidental finding that one of the 12 questions is ambiguous. MATERIALS AND METHODS: As part of a 10-year follow-up of patients treated with hip resurfacing the OHS was posted to 148 patients; 135 (91%) replied. Scores were read by 2 orthopaedic surgery trainees and entered into a database. It was noted that Question 5 was frequently mis-interpreted. RESULTS: Thirteen patients' questionnaires (10%) showed the same inconsistency: question 5 was scored as 0 points but the other 11 questions were scored as either 3 or 4 in 97% of cases. The ethnic group of all 13 patients was recorded in hospital data as being White-British. CONCLUSION: Question 5 of the OHS is ambiguous to 10% of native English-speakers. These patients rated their hip function highly, as reflected by the fact that 97% of the questions other than question 5 scored 3 or 4, indeed 87% of them scored 4. We hypothesise that the wording of the zero score option "Not at all" is being mis-interpreted as a response indicating that the patient does not suffer any pain at all. The effect is an error of 4 points out of 48 (8%); this may under-estimate the patient's hip score. Surgeons are under great scrutiny to prove efficacy of surgical interventions; this is often provided by PROMs. We should strive to formulate the most accurate, reproducible and least ambiguous PROMs questionnaires.

4.
J Environ Manage ; 213: 1-10, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29477845

RESUMO

Despite calls for more socio-technical research on energy, there is little practical advice to how narratives collected through qualitative research may be melded with technical knowledge from the physical sciences such as engineering and then applied in energy efficiency social action strategies. This is despite established knowledge in the environmental management literature about domestic energy use regarding the utility of social practice theory and narrative framings that socialise everyday consumption. Storytelling is positioned in this paper both as a focus for socio-technical energy research, and as one potential practical tool that can arguably enhance energy efficiency interventions. We draw upon the literature on everyday social practices, and storytelling, to present our framework called 'collective video storytelling' that combines scientific and lay knowledge about domestic energy use to offer a practical tool for energy efficiency management. Collective video storytelling is discussed in the context of Energy+Illawarra, a 3-year cross-disciplinary collaboration between social marketers, human geographers, and engineers to target energy behavioural change within older low-income households in regional NSW, Australia.


Assuntos
Comunicação , Conservação de Recursos Energéticos , Marketing Social , Austrália , Humanos , Narração , Pesquisa Qualitativa
5.
PLoS Pathog ; 12(9): e1005885, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27658293

RESUMO

Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.


Assuntos
Interações Hospedeiro-Patógeno/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Progestinas/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/efeitos dos fármacos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/imunologia , Colo do Útero/metabolismo , Colo do Útero/virologia , Preparações de Ação Retardada , Feminino , Injeções Intramusculares , Ativação Linfocitária/efeitos dos fármacos , Macaca mulatta , Macaca nemestrina , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/virologia , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/uso terapêutico , Ciclo Menstrual , Membrana Mucosa/imunologia , Membrana Mucosa/metabolismo , Membrana Mucosa/virologia , Progestinas/administração & dosagem , Progestinas/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/imunologia , Vagina/metabolismo , Vagina/virologia , Internalização do Vírus/efeitos dos fármacos
6.
J Acquir Immune Defic Syndr ; 72(4): 363-71, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27355414

RESUMO

INTRODUCTION: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). METHODS: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. RESULTS: It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). CONCLUSIONS: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/farmacologia , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/virologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Macaca nemestrina , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
7.
J Neurol Neurosurg Psychiatry ; 87(9): 968-74, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26818730

RESUMO

Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients.

8.
Int J Occup Med Environ Health ; 29(2): 229-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26670354

RESUMO

OBJECTIVES: The Health Impact Assessment (HIA) was conducted to evaluate the potential community health implications of a proposed oil drilling and production project in Hermosa Beach, California. The HIA considered 17 determinants of health that fell under 6 major categories (i.e., air quality, water and soil quality, upset conditions, noise and light emissions, traffic, and community livability). MATERIAL AND METHODS: This paper attempts to address some of the gaps within the HIA practice by presenting the methodological approach and results of this transparent, comprehensive HIA; specifically, the evaluation matrix and decision-making framework that have been developed for this HIA and form the basis of the evaluation and allow for a clear conclusion to be reached in respect of any given health determinant (i.e., positive, negative, neutral). RESULTS: There is a number of aspects of the project that may positively influence health (e.g., increased education funding, ability to enhance green space), and at the same time there have been potential negative effects identified (e.g., odor, blowouts, property values). Except for upset conditions, the negative health outcomes have been largely nuisance-related (e.g., odor, aesthetics) without irreversible health impacts. The majority of the health determinants, that had been examined, have revealed that the project would have no substantial effect on the health of the community. CONCLUSIONS: Using the newly developed methodology and based on established mitigation measures and additional recommendations provided in the HIA, the authors have concluded that the project will have no substantial effect on community health. This approach and methodology will assist practitioners, stakeholders and decision-makers in advancing the HIA as a useful, reproducible, and informative tool.


Assuntos
Avaliação do Impacto na Saúde/métodos , Política de Saúde , Promoção da Saúde/métodos , Doenças Profissionais/prevenção & controle , Indústria de Petróleo e Gás , California/epidemiologia , Humanos , Incidência , Doenças Profissionais/epidemiologia
9.
Sex Transm Dis ; 42(12): 694-701, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26562699

RESUMO

BACKGROUND: HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. METHODS: Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. RESULTS: In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). CONCLUSIONS: These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.


Assuntos
Ciclo Menstrual , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/isolamento & purificação , Vagina/patologia , Vagina/virologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epitélio/patologia , Epitélio/virologia , Feminino , Macaca nemestrina , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/patologia
12.
J Med Primatol ; 44(5): 286-95, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26238265

RESUMO

BACKGROUND: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. METHODS: Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. RESULTS: All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 µm in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 µm for the descending doses, respectively. CONCLUSIONS: All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Macaca nemestrina , Acetato de Medroxiprogesterona/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças/virologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ciclo Menstrual/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Progesterona/metabolismo , Vagina/anatomia & histologia
13.
J Med Primatol ; 44(5): 301-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26054016

RESUMO

Varying susceptibility during menstrual cycling could be a factor for S(H)IV infection risk in female rhesus macaques. We retrospectively determined vaginal SIV infection time points relative to the menstrual cycle in a group of rhesus macaques (n=11) enrolled in an HIV transmission trial. Eight of nine rhesus macaques became infected around menstruation time.


Assuntos
Macaca mulatta , Ciclo Menstrual , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Vagina/virologia , Animais , Feminino , Estudos Retrospectivos
14.
J Acquir Immune Defic Syndr ; 69(4): 385-94, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25886925

RESUMO

BACKGROUND: Preexposure prophylaxis (PrEP) for HIV prevention is a novel biomedical prevention method. We have previously modeled PrEP during rectal SHIV exposures in macaques and identified that Simian/Human Immunodeficiency Virus chimera (SHIV)-specific T-cell responses were induced in the presence of antiretroviral drugs, an observation previously termed T-cell chemo-vaccination. This report expands those initial findings by examining a larger group of macaques that were given oral or topical PrEP during repeated vaginal virus exposure. METHODS: Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild-type (WT) SHIVSF162P3 (n = 24) or a clonal derivative with the tenofovir (TFV) K65R drug-resistant mutation (n = 12). PrEP consisted of oral Truvada (n = 6, WT), TFV vaginal gel (n = 6, K65R), or TFV intravaginal ring (n = 6, WT). The remaining animals were PrEP-inexperienced controls (n = 12, WT; n = 6, K65R). SHIV-specific T cells were identified and characterized using interferon γ Enzyme-Linked ImmunoSpot (ELISPOT) and multiparameter flow cytometry. RESULTS: Of 9 animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, 8 (88.9%) developed virus-specific T-cell responses. T cells were in CD4 and CD8 compartments, reached up to 4900 interferon γ-producing cells per million peripheral blood mononuclear cells, and primarily pol directed. In contrast, the replication-impaired K65R virus did not induce detectable T-cell responses, likely reflecting the need for adequate replication. CONCLUSIONS: Virus-specific T-cell responses occur frequently in oral or topical PrEP-protected pigtail macaques after vaginal exposure to WT SHIV virus. The contribution of such immune responses to protection from infection during and after PrEP warrants further investigation.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Desoxicitidina/análogos & derivados , Infecções por HIV/prevenção & controle , Macaca nemestrina , Compostos Organofosforados , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Linfócitos T/fisiologia , Administração Oral , Administração Tópica , Animais , Combinação de Medicamentos , Farmacorresistência Viral , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila , Feminino , Profilaxia Pré-Exposição , Vírus Reordenados/efeitos dos fármacos , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/imunologia
15.
J Med Primatol ; 44(2): 97-107, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25536296

RESUMO

BACKGROUND: Injectable hormonal contraception may increase women's risk of HIV acquisition and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. METHODS: Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 18 weeks. RESULTS: Mean vaginal epithelial thicknesses were 290.8 µm at baseline and 186.2 µm during COC (P = 0.0141, Mann-Whitney U-test). Vaginal pH decreased from 8.5 during treatment to 6.5 post-treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. CONCLUSIONS: COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + .0066 mg EE appeared effective in suppressing ovulation.


Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Suscetibilidade a Doenças/induzido quimicamente , Etinilestradiol/farmacologia , Infecções por HIV/fisiopatologia , Levanogestrel/farmacologia , Membrana Mucosa/efeitos dos fármacos , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Animais , Anticoncepcionais Orais Combinados/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças/fisiopatologia , Relação Dose-Resposta a Droga , Etinilestradiol/efeitos adversos , Feminino , Levanogestrel/efeitos adversos , Macaca nemestrina , Ciclo Menstrual/efeitos dos fármacos , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/efeitos dos fármacos
17.
AIDS Res Hum Retroviruses ; 30(11): 1125-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25313448

RESUMO

The repeat low-dose virus challenge model is commonly used in nonhuman primate studies of HIV transmission and biomedical preventions. For some viruses or challenge routes, it is uncertain whether the repeated exposure design might induce virus-directed innate or adaptive immunity that could affect infection or viremic outcomes. Retrospective cohorts of male Indian rhesus (n=40) and female pigtail (n=46) macaques enrolled in repeat low-dose rectal or vaginal SHIV(SF162p3) challenge studies, respectively, were studied to compare the relationship between the number of previous exposures and peak plasma SHIV RNA levels or viral load area under the curve (AUC), surrogate markers of viral control. Repeated mucosal exposures of 10 or 50 TCID50 of virus for rectal and vaginal exposures, respectively, were performed. Virus levels were measured by quantitative reverse-transcriptase real-time PCR. The cumulative number of SHIV(SF162p3) exposures did not correlate with observed peak virus levels or with AUC in rectally challenged rhesus macaques [peak: rho (ρ)=0.04, p=0.8; AUC: ρ=0.33, p=0.06] or vaginally challenged pigtail macaques (peak: ρ=-0.09, p=0.7; AUC: ρ=0.11, p=0.6). Infections in these models occur independently of exposure history and provide assurance that neither inoculation route nor number of exposures required for infection correlates with postinfection viremia. These data also indicate that both the vaginal and rectal repeated low-dose virus exposure models using SHIV(SF162p3) provide a reliable system for nonhuman primate studies.


Assuntos
HIV/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Carga Viral , Animais , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Macaca mulatta , Macaca nemestrina , Masculino , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
BMJ Open ; 4(10): e006291, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25354825

RESUMO

OBJECTIVE: To evaluate maternal and neonatal outcomes associated with operative vaginal deliveries (OVDs) performed by day and at night. DESIGN: Prospective cohort study. SETTING: Urban maternity unit in Ireland with off-site consultant staff at night. POPULATION: All nulliparous women requiring an OVD with a term singleton fetus in a cephalic presentation from February to November 2013. METHODS: Delivery outcomes were compared for women who delivered by day (08:00-19:59) or at night (20:00-07:59). MAIN OUTCOME MEASURES: The main outcomes included postpartum haemorrhage (PPH), anal sphincter tear and neonatal unit admission. Procedural factors included operator grade, sequential use of instruments and caesarean section. RESULTS: Of the 597 women who required an OVD, 296 (50%) delivered at night. Choice of instrument, place of delivery, sequential use of instruments and caesarean section did not differ significantly in relation to time of birth. Mid-grade operators performed less OVDs by day than at night, OR 0.60 (95% CI 0.43 to 0.83), and a consultant supervisor was more frequently present by day, OR 2.26 (95% CI 1.05 to 4.83). Shoulder dystocia occurred more commonly by day, OR 2.57 (95% CI 1.05 to 6.28). The incidence of PPH, anal sphincter tears, neonatal unit admission, fetal acidosis and neonatal trauma was similar by day and at night. The mean decision to delivery intervals were 12.0 and 12.6 min, respectively. CONCLUSIONS: There was no evidence of an association between time of OVD and adverse perinatal outcomes despite off-site consultant obstetric support at night.


Assuntos
Canal Anal/lesões , Traumatismos do Nascimento/epidemiologia , Extração Obstétrica/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Lacerações/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Adulto , Estudos de Coortes , Distocia , Feminino , Humanos , Recém-Nascido , Irlanda , Masculino , Paridade , Admissão e Escalonamento de Pessoal , Gravidez , Estudos Prospectivos , Fatores de Tempo
19.
J Med Primatol ; 43(5): 310-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24779484

RESUMO

BACKGROUND: Hormonal changes during menstrual cycling may affect susceptibility to HIV. METHODS: We determined the simian human immunodeficiency virus (SHIV) acquisition time point in 43 cycling pigtail macaques infected by repeated vaginal virus exposures initiated randomly in the cycle. RESULTS: SHIV infection was first detected in the follicular phase in 38 macaques (88%), and in the luteal phase in five macaques (12%), indicating a statistically significant timing difference. Assuming a 7-day eclipse phase, most infections occurred during or following a high-progesterone period associated with menstruation, vaginal epithelium thinning, and suppressed mucosal immunity. CONCLUSIONS: This raises questions whether other high-progesterone conditions (pregnancy, hormonal contraception) similarly affect HIV risk.


Assuntos
Suscetibilidade a Doenças/imunologia , Macaca nemestrina , Ciclo Menstrual/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Animais , Suscetibilidade a Doenças/virologia , Feminino , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Fatores de Tempo , Vagina/virologia
20.
J Infect Dis ; 210(8): 1239-47, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24755433

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood. METHODS: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. RESULTS: Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test). CONCLUSIONS: C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.


Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis , Coinfecção/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Vaginite por Trichomonas/complicações , Trichomonas vaginalis , Animais , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/patologia , Colposcopia , Feminino , Macaca nemestrina , Fatores de Risco , Doenças Sexualmente Transmissíveis/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
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