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1.
Am J Pharm Educ ; 87(8): 100013, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37597910

RESUMO

OBJECTIVES: Curriculum overload often occurs when content is kept in the curriculum that may no longer be necessary to prepare students for professional practice. The overload becomes compounded by the addition of new content from the ever-changing professional practice needs and updates to accreditation standards. Challenges may occur when programs must first determine the "level" of proficiency a new graduate should attain and then determine the appropriate breadth and depth of educational outcomes in relation to proficiency, while examining what content should be retained from past curricula. Thus, the purpose of this manuscript is to summarize institutional approaches for making content delivery more effective and efficient with the goal of curtailing curriculum expansion. FINDINGS: Four key elements were consistently identified in the literature as important considerations to address curriculum overload - 1) communication and coordination among faculty, 2) incorporation of active learning strategies, 3) effective utilization of technology, and 4) minimizing faculty and student workload and cognitive burden. SUMMARY: Each pharmacy program will need to take an individualized approach in addressing curriculum overload; however, consideration of the aforementioned key elements can assist in making these decisions. With increased student engagement in the classroom, intentional design to reduce content and student workload, enhanced communication among faculty, and appropriate technology utilization, curriculum overload can be addressed at every level of pharmacy education.


Assuntos
Educação em Farmácia , Humanos , Currículo , Estudantes , Docentes , Escolaridade
2.
Curr Rev Clin Exp Pharmacol ; 17(3): 192-204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34455951

RESUMO

BACKGROUND: Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning. METHODS: This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies. RESULTS: Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high. CONCLUSION: Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.


Assuntos
Rodenticidas , Acetilcisteína/uso terapêutico , Humanos , Estudos Prospectivos , Estudos Retrospectivos
3.
Data Brief ; 35: 106938, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33748369

RESUMO

A survey about orientations, boot camps, and pre-matriculation programs in schools/colleges of pharmacy was approved by the South College Institutional Review Board (IRB). The survey was sent electronically to Assistant/Associate Deans of Academic Affairs or administrators in similar positions at schools/colleges of pharmacy in October 2016. The survey was closed two months later, in December, with 50 responses. The data that was collected from the survey included characteristics and components of orientations, boot camps, and pre-matriculation programs, such as session content and the frequency sessions appeared. The survey also collected descriptive information from respondents regarding certain demographics related to their schools/colleges of pharmacy (e.g., public or private institutions, a 4-year program or a 3-year program). The data can be used by schools/colleges of pharmacy and other healthcare professions that wish to revise or establish orientations, boot camps, and pre-matriculation programs.

4.
Curr Rev Clin Exp Pharmacol ; 16(2): 201-208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32400335

RESUMO

RATIONALE & OBJECTIVE: Rodenticide poisoning, either accidental or intentional, is very common in rural India. The absence of a definite antidote made it a major concern with a high mortality rate. Therefore, this study aimed to assess the effectiveness of N-Acetyl Cysteine (NAC) in rodenticide poisoning as there are recent positive shreds of evidence on it. METHODOLOGY: A retrospective study was conducted in a tertiary care teaching hospital on patients admitted with rodenticide poisoning during a period of 2012-2017. The Fischer's exact test and relative risk were measured to analyze the outcome of treatment and risk factors, respectively. RESULTS: A total of 229 patients were enrolled in the study with a mean age of 30.04 ± 15.67 years. The suicidal attack was the major (86.0%) reason for poison consumption. The survival rate was significantly (p ≤ 0.03) higher in the NAC treatment group compared to the non-NAC group. Moreover, the majority (93.4%) of participants did not experience any adverse effects. The mean oral loading dose and maintenance dose was 7580.95 ± 2204.29 mg and 3694.53 ± 2322.58 mg, respectively. Yellow Phosphorus poisoning (Relative Risk [RR] 2.888 (1.179-7.079); p=0.020) and Time lag of ≥ 24 hours (RR 3.479 (1.137-10.645); p=0.029) were the significant risk factors for mortality. CONCLUSION: NAC is shown to have a significant survival benefit with a good safety profile among rodenticide poisoners. Further adequately powered prospective researches with more emphasis on dosing parameters are warranted for better quantification in different settings and for clinical implementation.


Assuntos
Acetilcisteína , Rodenticidas , Acetilcisteína/uso terapêutico , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Atenção Terciária à Saúde , Adulto Jovem
5.
Am J Pharm Educ ; 83(7): 7021, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31619823

RESUMO

Objective. To characterize the development, revision, and student perceptions of a pre-matriculation program entitled Pharmacy Readiness and Enrichment Program (PREP) in a school of pharmacy. Methods. The program was first implemented in June 2013 for the incoming class of 2016. The main components of PREP were curriculum and scientific content review, professionalism, time management, critical thinking, and personal interactions. Entering student pharmacists were surveyed immediately and six or more months after PREP concluded. Statistical analysis was performed to determine if participation in PREP affected students' academic performance. Results. Student perceptions regarding the program and its components were favorable immediately after PREP but less favorable six or more months later. Statistical analysis showed that students who completed PREP had significantly higher cumulative grade point average (GPA) in pharmacy year one and year two. Conclusion. It is possible to implement a two-day pre-matriculation program with a wide range of components and deliver it prior to the start of the first professional year. It is also possible to deliver some PREP components during the first professional year rather than prior to matriculation into the program. The PREP may serve as a model for other schools of pharmacy that are considering the implementation of a pre-matriculation program, or that have a pre-matriculation program in place and are seeking to modify or update their program.


Assuntos
Currículo , Educação em Farmácia/métodos , Faculdades de Farmácia , Estudantes de Farmácia/psicologia , Desempenho Acadêmico , Humanos , Profissionalismo , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
6.
MMWR Morb Mortal Wkly Rep ; 65(5): 110-4, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26866344

RESUMO

In 2014, the California Department of Public Health was notified by a local health department of a diagnosis of acute human immunodeficiency virus (HIV) infection* and rectal gonorrhea in a male adult film industry performer, aged 25 years (patient A). Patient A had a 6-day history of rash, fever, and sore throat suggestive of acute retroviral syndrome at the time of examination. He was informed of his positive HIV and gonorrhea test results 6 days after his examination. Patient A had a negative HIV-1 RNA qualitative nucleic acid amplification test (NAAT)(†) 10 days before symptom onset. This investigation found that during the 22 days between the negative NAAT and being informed of his positive HIV test results, two different production companies directed patient A to have condomless sex with a total of 12 male performers. Patient A also provided contact information for five male non-work-related sexual partners during the month before and after his symptom onset. Patient A had additional partners during this time period for which no locating information was provided. Neither patient A nor any of his interviewed sexual partners reported taking HIV preexposure prophylaxis (PrEP). Contact tracing and phylogenetic analysis of HIV sequences amplified from pretreatment plasma revealed that a non-work-related partner likely infected patient A, and that patient A likely subsequently infected both a coworker during the second film production and a non-work-related partner during the interval between his negative test and receipt of his positive HIV results. Adult film performers and production companies, medical providers, and all persons at risk for HIV should be aware that testing alone is not sufficient to prevent HIV transmission. Condom use provides additional protection from HIV and sexually transmitted infections (STIs). Performers and all persons at risk for HIV infection in their professional and personal lives should discuss the use of PrEP with their medical providers.


Assuntos
Infecções por HIV/transmissão , Filmes Cinematográficos , Doenças Profissionais/epidemiologia , Adulto , Humanos , Masculino , Comportamento Sexual/estatística & dados numéricos , Estados Unidos/epidemiologia , Sexo sem Proteção/estatística & dados numéricos
7.
Ugeskr Laeger ; 176(12A)2014 Mar 17.
Artigo em Dinamarquês | MEDLINE | ID: mdl-25350889

RESUMO

Accumulating evidence suggests that obesity has a negative impact on breast cancer survivors. In this project we developed and tried out a residential 6 + 3 days rehabilitation programme with focus on weight reduction for breast cancer survivors. The key focus was to work with their motivation to change habits by use of cognitive therapy tools. It seems that this residential rehabilitation stay can motivate obese breast cancer survivors to change habits and lose weight. In all the 42 women with complete data lost 6.1 kg in average.


Assuntos
Neoplasias da Mama/reabilitação , Obesidade/reabilitação , Redução de Peso , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Terapia Cognitivo-Comportamental , Terapia por Exercício , Feminino , Humanos , Comunicação Interdisciplinar , Estilo de Vida , Motivação , Obesidade/psicologia , Centros de Reabilitação , Inquéritos e Questionários , Resultado do Tratamento
8.
Antimicrob Agents Chemother ; 58(9): 5016-23, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24709264

RESUMO

Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.


Assuntos
Géis/administração & dosagem , Herpes Simples/tratamento farmacológico , Imidazóis/administração & dosagem , Simplexvirus/efeitos dos fármacos , Aciclovir/administração & dosagem , Aciclovir/análogos & derivados , Adolescente , Adulto , Idoso , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Herpes Simples/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Valaciclovir , Valina/administração & dosagem , Valina/análogos & derivados , Cicatrização/efeitos dos fármacos , Adulto Jovem
9.
Elife ; 2: e00288, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23606943

RESUMO

Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium. DOI:http://dx.doi.org/10.7554/eLife.00288.001.


Assuntos
Linfócitos T CD8-Positivos/virologia , DNA Viral/biossíntese , Genitália/virologia , Herpes Genital/virologia , Herpesvirus Humano 2/fisiologia , Ativação Viral , Linfócitos T CD8-Positivos/imunologia , Simulação por Computador , Genitália/imunologia , Herpes Genital/imunologia , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/imunologia , Interações Hospedeiro-Patógeno , Humanos , Cinética , Modelos Imunológicos , Carga Viral , Eliminação de Partículas Virais
10.
PLoS One ; 8(2): e55002, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23405106

RESUMO

INTRODUCTION: Accurate estimates of HIV incidence are crucial for prioritizing, targeting, and evaluating HIV prevention efforts. Using the methodology the CDC used to estimate national HIV incidence, we estimated HIV incidence in Los Angeles County (LAC), San Francisco (SF), and California's remaining counties. METHODS: We estimated new HIV infections in 2006-2009 among adults and adolescents in LAC, SF and the remaining California counties using the Serologic Testing Algorithm for Recent Seroconversion (STARHS). STARHS methodology uses the BED HIV-1 capture enzyme immunoassay to determine recent HIV infections by testing remnant serum from persons newly diagnosed with HIV. A population-based incidence estimate is calculated using HIV testing data from newly diagnosed cases and imputing for persons unaware of their HIV infection. RESULTS: For years 2007-2009, respectively, we estimated new infections in LAC to be 2426 (95% CI 1871-2982), 1669 (CI 1309-2029) and 1898 (CI 1452-2344) (p<0.01); in SF for 2006-2009, 492 (CI 327-657), 490 (CI 335-646), 458 (CI 342-574) and 367 (CI 261-473) (p = 0.14); and in the remaining California counties in 2008-2009, 2526 (CI 1688-3364) and 2993 (CI 2141-3846) respectively. HIV infection rates among men who have sex with men (MSM) in LAC were 100 times higher than other risk populations; the SF MSM rate was 3 to 18 times higher than other demographic groups. In LAC, incidence rates among African-Americans were twice those of whites and Latinos; persons 40 years or older had lower rates of infection than younger persons. DISCUSSION: We report the first HIV incidence estimates for California, highlighting geographic disparities in HIV incidence and confirming national findings that MSM and African-Americans are disproportionately impacted by HIV. HIV incidence estimates can and should be used to target prevention efforts towards populations at highest risk of acquiring new HIV infections, focusing on geographic, racial and risk group disparities.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/diagnóstico , Adolescente , Adulto , California/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Incidência , Masculino , Comportamento Sexual/psicologia , Adulto Jovem
11.
Open AIDS J ; 6: 188-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23049669

RESUMO

INTRODUCTION: The Medical Monitoring Project (MMP) is a national, multi-site population-based supplemental HIV/AIDS surveillance project of persons receiving HIV/AIDS care. We compared California MMP data by region. Demographic characteristics, medical care experiences, HIV treatment, clinical care outcomes, and need for support services are described. METHODS: HIV-infected patients 18 years or older were randomly selected from medical care facilities. In person structured interviews from 2007 - 2008 were used to assess sociodemographic characteristics, self-reported clinical outcomes, and need for supportive services. Pearson chi-squared, Fisher's exact and Kruskal-Wallis p-values were calculated to compare regional differences. RESULTS: Between 2007 and 2008, 899 people were interviewed: 329 (37%) in San Francisco (SF), 333 (37%) in Los Angeles (LA) and 237 (26%) in other California counties. Significant regional sociodemographic differences were found. Care received and clinical outcomes for patients in MMP were positive and few regional differences were identified. HIV case management (36%), mental health counseling (35%), and dental services (29%) were the supportive services patients most frequently needed. Unmet needs for supportive services were low overall. Significant differences by region in needed and unmet need services were identified. DISCUSSION: The majority of MMP respondents reported standard of care CD4 and viral load monitoring, high treatment use, undetectable HIV viral loads and CD4 counts indicative of good immune function and treatment efficacy. Information from MMP can be used by planning councils, policymakers, and HIV care providers to improve access to care and prevention. Identifying regional differences can facilitate sharing of best practices among health jurisdictions.

12.
J Virol ; 86(18): 9952-63, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22761381

RESUMO

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Herpes Genital/imunologia , Herpes Genital/virologia , Herpesvirus Humano 2/imunologia , Herpesvirus Humano 2/patogenicidade , Adulto , Idoso , Contagem de Células , Estudos de Coortes , Citocinas/metabolismo , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Feminino , Herpes Genital/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Eliminação de Partículas Virais/imunologia , Adulto Jovem
13.
Microvasc Res ; 84(2): 161-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22633841

RESUMO

α1-Acid glycoprotein (AGP) is a positive acute phase protein which is elevated 1-10 times during inflammation. Whereas AGP has been reported to have immunomodulatory properties, other biological functions of this protein such as its effects on the blood-brain barrier (BBB) endothelium are unknown. Tight junction (TJ) proteins (ZO-1 and occludin) are crucial in maintaining BBB integrity and brain homeostasis. As inflammatory cytokines have been shown to alter BBB integrity and TJ protein expression, we hypothesized that AGP changes BBB function by stimulating inflammatory cytokines and/or directly modulating TJ protein expression. We used primary rat brain microvessel endothelial cells (RBMECs) as an in vitro BBB model to study the direct effects of AGP on the brain microvasculature. No change in cytokine levels was detected in supernatant from AGP-treated RBMECs, despite increased mRNA expression by the cells. Paracellular permeability was decreased up to 20%, across RBMEC monolayers following treatment with AGP, suggesting its role in enhancing BBB integrity. RBMECs showed a biphasic response of increased occludin protein expression following AGP treatment while ZO-1 expression changed in a dose- and time-dependent manner. These changes in TJ proteins suggest that AGP induced changes in occludin related to enhanced barrier properties while the change in ZO-1 may play a secondary role in BBB integrity and/or as an intracellular signaling molecule. AGP significantly changed transcription factor activator protein 1 (AP-1) DNA-binding activity which provides evidence of the potential cell signaling pathways that contribute to the effect of AGP in RBMECs. Together, this supports our hypothesis that AGP has a direct effect in brain microvasculature and may play an important role in altering BBB integrity in inflammatory-related diseases.


Assuntos
Barreira Hematoencefálica/metabolismo , Encéfalo/irrigação sanguínea , Permeabilidade Capilar , Células Endoteliais/metabolismo , Microvasos/metabolismo , Orosomucoide/metabolismo , Animais , Sítios de Ligação , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/imunologia , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais/imunologia , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Microvasos/citologia , Microvasos/imunologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo
14.
J Acquir Immune Defic Syndr ; 57(3): 238-44, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21860356

RESUMO

INTRODUCTION: Extensive observational data suggest that herpes simplex virus type 2 (HSV-2) infection may facilitate HIV acquisition, increase HIV viral load, and accelerate HIV progression and onward transmission. To explore these relationships, we examined the impact of preexisting HSV-2 infection in an international HIV vaccine trial. METHODS: We analyzed the associations between prevalent HSV-2 infection and HIV-1 acquisition and progression among 1836 men who have sex with men. We used Cox proportional hazards regression models to estimate the association between HSV-2 infection and both HIV acquisition and antiretroviral therapy (ART) initiation, and linear regression to explore the effect of HSV-2 on pre-ART viral load. RESULTS: HSV-2 infection increased risk of HIV-1 acquisition among all volunteers [adjusted hazard ratio 2.2; 95% confidence interval (CI): 1.4 to 3.5]. Adjusting for demographic variables, circumcision, Ad5 titer, and significant risk behaviors, the risk of HIV acquisition among HSV-2-infected placebo recipients was 3-fold higher than HSV-2 seronegatives (adjusted hazard ratio 3.3; 95% CI: 1.6 to 6.9). Past HSV-2 infection was associated with a 0.2 log10 copies per milliliter higher adjusted mean set point viral load (95% CI: 0.3 lower to 0.6 higher). HSV-2 infection was not associated with time to ART initiation. CONCLUSIONS: Among men who have sex with men in an HIV-1 vaccine trial, preexisting HSV-2 infection was a major risk factor for HIV acquisition. Past HSV-2 did not significantly increase HIV viral load or early disease progression. HSV-2-seropositive persons will likely prove more difficult than HSV-2-seronegative persons to protect against HIV infection using vaccines or other prevention strategies.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , HIV-1/imunologia , Herpes Simples/complicações , Herpesvirus Humano 2/imunologia , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Herpes Simples/imunologia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carga Viral , Adulto Jovem
15.
Proc Natl Acad Sci U S A ; 107(44): 18973-8, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20956313

RESUMO

Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8(+) lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8(+) lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8(+) T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8(+) lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Herpes Genital/imunologia , Herpesvirus Humano 2/fisiologia , Imunidade nas Mucosas , Modelos Imunológicos , Replicação Viral/imunologia , Eliminação de Partículas Virais/imunologia , Biópsia , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Estudos de Coortes , DNA Viral/imunologia , Feminino , Herpes Genital/patologia , Herpes Genital/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Masculino , Mucosa/imunologia , Mucosa/patologia , Mucosa/virologia
16.
J Acquir Immune Defic Syndr ; 54(5): 482-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20616743

RESUMO

OBJECTIVE: To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults. METHODS: Twenty HSV-2-seropositive, HIV-seropositive adults, including 9 (45%) who were also HSV-1 seropositive, collected oral and anogenital swabs for HSV DNA polymerase chain reaction 4 times a day for 60 days. Samples were positive for HSV if we detected > or =150 copies of HSV DNA/mL of specimen. RESULTS: Median HSV shedding episode duration was 7.5 (range 4-253) hours for oral and 11 (range 4-328) hours for anogenital reactivation. Thirty-five percent of oral and 29% of anogenital reactivations lasted < or =6 hours, and 59% of oral and 53% of anogenital reactivations lasted < or =12 hours. Seven of 9 participants who shed orally and 10 of 15 who shed anogenitally had > or =1 reactivation lasting < or =6 hours. The median maximum level of HSV DNA detected in an episode increased with episode duration for both oral and anogenital episodes. Concurrent oral and anogenital shedding occurred more frequently than expected: oral HSV shedding was detected on 17% of time points with anogenital but 1% of time points without anogenital, shedding (P < 0.001). CONCLUSIONS: Rapidly cleared episodes of oral and anogenital HSV shedding occur in HIV-infected persons, supporting the hypothesis that frequent anogenital mucosal immune activation caused by HSV-2 is present in HIV coinfected persons, potentially contributing to HIV infectiousness.


Assuntos
Canal Anal/virologia , Infecções por HIV/complicações , Herpes Simples/epidemiologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Boca/virologia , Eliminação de Partículas Virais , Adulto , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Ativação Viral
17.
Sci Transl Med ; 1(7): 7ra16, 2009 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-20161655

RESUMO

Herpes simplex virus-2 (HSV-2) is a sexually transmitted infection that is the leading cause of genital ulcers worldwide. Infection is life long and is characterized by repeated asymptomatic and symptomatic shedding episodes of virus that are initiated when virus is released from neurons into the genital tract. The pattern of HSV-2 release from neurons into the genital tract is poorly understood. We fit a mathematical model of HSV-2 pathogenesis to curves generated from daily quantification of HSV in mucosal swabs performed from patients with herpetic genital ulcers. We used virologic parameters derived from model fitting for stochastic model simulations. These simulations reproduced previously documented estimates for shedding frequency, and herpetic lesion diameter and frequency. The most realistic model output occurred when we assumed minimal amounts of daily neuronal virus introduction. In our simulations, small changes in average total quantity of HSV-2 released from neurons influenced detectable shedding frequency, while changes in frequency of neuronal HSV-2 release had little effect. Frequent HSV-2 shedding episodes in humans are explained by nearly constant release of small numbers of viruses from neurons that terminate in the genital tract.


Assuntos
Herpesvirus Humano 2/fisiologia , Modelos Teóricos , Neurônios/virologia , Herpes Genital/virologia , Humanos , Processos Estocásticos , Eliminação de Partículas Virais
18.
J Infect Dis ; 198(8): 1141-9, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18783315

RESUMO

BACKGROUND: Herpes simplex virus (HSV) remains latent in nerve root ganglia of infected persons and is thought to reactivate several times yearly. Recent in situ data show the localization of HSV-specific CD8(+) T cells at the dermal epidermal junction next to peripheral sensory nerve endings, suggesting that viral reactivation may occur more frequently than previously appreciated. METHODS: Twenty-five HSV-2-seropositive and 18 HSV-1-seropositive healthy adults collected anogenital and oral swabs, respectively, 4 times per day for 60 days. Swabs were assayed for HSV, using a quantitative polymerase chain reaction assay. RESULTS: Twenty-four percent of anogenital reactivations and 21% of oral reactivations lasted < or =6 h, and 49% of anogenital reactivations and 39% of oral reactivations lasted < or =12 h. Lesions were reported in only 3 (7%) of 44 anogenital reactivations and 1 (8%) of 13 oral reactivations lasting < or =12 h. The median HSV DNA levels at initial and last detection were 10(3.5) and 10(3.3) copies/mL, respectively, during anogenital reactivation and 10(3.7) and 10(3.0) copies/mL, respectively, during oral reactivation. CONCLUSIONS: This high frequency of short subclinical HSV reactivation in immunocompetent hosts strongly suggests that the peripheral mucosal immune system plays a critical role in clearing HSV reactivations.


Assuntos
Herpes Genital/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Ativação Viral/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Feminino , Genitália/virologia , Herpes Genital/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Humanos , Imunocompetência , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/virologia , Fatores de Tempo , Eliminação de Partículas Virais
19.
Sex Transm Dis ; 35(11): 960-5, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18685548

RESUMO

BACKGROUND: Little data exist on Internet and email use among STD clinic patients for research and clinical care communication. METHODS: An anonymous cross-sectional survey of STD clinic patients aged >/=18 years in Seattle, WA, March 13 to 22, 2006. RESULTS: Of 489 study period patients, 251 (51%) completed the questionnaire. Participants had a median age of 30 (range 18-66) years and were 69% male, 56% white, 19% black, 9% Hispanic, and 7% Asian/Pacific Islander. Of all participants, 75% had some postsecondary education but half reported an annual income of

Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Atenção à Saúde/métodos , Correio Eletrônico/estatística & dados numéricos , Internet/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Idoso , Pesquisa Biomédica/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Washington , Adulto Jovem
20.
Microvasc Res ; 75(1): 91-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17651765

RESUMO

The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of (14)C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6-18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1beta, TNFalpha, IL-6, IL-10, and IFNgamma) demonstrated that only IL-1beta and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min-3 h), increases in monocytes (10 min-3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.


Assuntos
Barreira Hematoencefálica/metabolismo , Edema Encefálico/etiologia , Permeabilidade Capilar , Hipóxia/metabolismo , Estresse Oxidativo , Animais , Edema Encefálico/sangue , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Radioisótopos de Carbono , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Hipóxia/complicações , Contagem de Leucócitos , Ratos , Ratos Sprague-Dawley , Sacarose/metabolismo , Fatores de Tempo
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