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2.
Am J Infect Control ; 51(12): 1360-1365, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37263420

RESUMO

BACKGROUND: Behavioral health settings present increased challenges in preventing the transmission of infectious agents. Characterizing the relative effectiveness of various strategies, including testing for asymptomatic carriage of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, will inform transmission reduction efforts in behavioral health settings. METHODS: A single-center retrospective study was conducted in an inpatient behavioral health hospital by reviewing COVID-19 mitigation and testing strategies with information collected from discharges between July 1, 2020 and February 28, 2021. RESULTS: During the study period, there were 3,694 total discharges and 3,229 unique admitted patients, including 86 (2.7%) patients who had positive SARS-CoV-2 polymerase chain reaction test results. Preadmission testing from noncongregate care settings (38, 44.1%), and testing after an in-hospital exposure (27, 31.4%) were the most common indications for testing among patients with a positive test. Up to 29 (33.7%) potentially acquired the infection during their hospitalization. Asymptomatic screening tests identified approximately two-thirds (55, 64.0%) of potentially contagious patients. CONCLUSION: Asymptomatic screening testing on admission and after exposure and universal masking were strong interventions to prevent SARS-CoV-2 transmission in this investigation Future studies of SARS-CoV-2 and other pathogens in behavioral health settings should endeavor to characterize the effectiveness of infection prevention interventions.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Hospitais Psiquiátricos
3.
J Nurs Adm ; 53(3): 154-160, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36821499

RESUMO

Registered nurse retention is declining, with a national turnover rate in 2021 of 27%. After implementing a toolkit, nursing leaders in 1 organization completed 75 stay interviews with nurses in a cardiothoracic telemetry and a cardiothoracic surgical intensive care unit. Nurses reported that unit culture, team/peers, and scheduling were important in decisions to stay in their positions, but respondents considered leaving for salary, growth/development, and traveling opportunities. The stay interview process affords nurse leaders an opportunity to examine why nurses stay or leave and supports the development of targeted retention strategies.


Assuntos
Enfermeiras e Enfermeiros , Humanos , Emprego , Reorganização de Recursos Humanos , Salários e Benefícios , Satisfação no Emprego
4.
J Vet Med Educ ; : e20220095, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36689690

RESUMO

Determining if an employment opportunity will be a good match can feel daunting, especially for veterinary graduates entering the workforce. To ease this transition, veterinary educators traditionally have attempted to provide career support through interspersed didactic lectures on career options and the preparation of employment documents. While well intended, this approach fails to address the multiple dimensions of effective career planning or the reality that career planning is a lifelong endeavor. For a career planning teaching modality to be effective, it must address all stages of career planning and provide a framework that can be adapted throughout a career. Here we describe how a four-stage career-planning model, utilized throughout higher education, was employed to create a career planning assignment for guiding students in assessing organizational fit. We describe how student feedback was used to inform revisions, resulting in an improved educational experience as measured by students' perceptions of the utility of the assignment. Additional recommendations based on instructor reflection are provided to guide creation and implementation of future assignments. Given the growing support for professional skills training in veterinary medical education, we view incorporation of such learning activities as essential to preparing students to enter the modern veterinary workplace.

5.
J Am Vet Med Assoc ; : 1-6, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843439

RESUMO

OBJECTIVE: To evaluate income and family planning decisions of American College of Zoological Medicine (ACZM) diplomates. SAMPLE: 98 ACZM diplomates. PROCEDURES: An online survey was sent to 201 ACZM diplomates. Participation was voluntary. RESULTS: 98 (49%) diplomates responded to the survey. The most commonly reported income categories were $90,000 to $94,999, $100,000 to $104,999, and $110,000 to $114,999. Overall, the mean of the salary-category midpoint responses was $105,357 but was $122,917 for those in academia and $94,508 for those working in zoos and aquaria. When incomes of males and females were matched (24 pairs matched for gender and age), no difference in income was observed. There were no significant differences in income between males and females with and without children. Diplomates who did not complete a residency had significantly higher incomes than diplomates who did. Sixteen of 21 (76%) females and 9 of 19 (47%) males reported delaying having children because of their career. Additionally, a higher percentage of females with children (13/20 [65%]) than males with children (3/19 [16%]) felt that having children had had a negative effect on their career. Thirty-five of 41 (85%) females without children and 4 of 9 (44%) males without children thought having children would have negatively affected their careers. CLINICAL RELEVANCE: Although substantial differences in income between female and male ACZM diplomates were not identified, differences in family planning and perceptions of the impact of having children on their careers did exist.

6.
J Vet Med Educ ; 49(2): 187-198, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33929298

RESUMO

Clinical clerkships have long been a pillar of veterinary medical education. These experiences provide students a unique opportunity to apply skills learned in pre-clinical training through hands-on practice. However, the emergence of the novel coronavirus, SARS-CoV-2, and the subsequent global pandemic of 2020 forced many clinical instructors to adapt to teaching online. This teaching tip describes the use of backward design to create a three-part online clinical learning environment for the delivery of small animal primary care consisting of synchronous rounds, simulated online appointments, and independent learning activities. Results of a survey of students' perspectives on the experience demonstrate that the majority of students found that the online clinical experience met or exceeded expectations and provided a meaningful learning experience. Recommendations based on student feedback and instructor reflection are provided to guide creation and implementation of future online clinical courses. As the field of telemedicine grows, we view incorporation of such learning environments into veterinary medical education curriculum as essential to preparing students to enter the modern veterinary workplace.


Assuntos
COVID-19 , Estágio Clínico , Educação em Veterinária , Animais , COVID-19/epidemiologia , COVID-19/veterinária , Humanos , Atenção Primária à Saúde , SARS-CoV-2
8.
Crit Care Nurs Q ; 44(3): 293-300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34010203

RESUMO

Organizational structures have been shifting in health care over the past decade. Although hierarchal structures exist in many hospitals and health care entities, matrix approaches have been implemented to complement the traditional reporting configuration. The institute model is a hybrid structure implemented within medical and surgical service lines to promote patient-centered care within a hospital network. Physician administrators lead the institutes with collaboration by key liaisons such as nursing and quality leaders. In order to be successful, the concepts must extend from the boardroom to the front line. Teams focused specifically on quality metrics were developed within the service lines using an interdisciplinary approach to promote engagement and achieve desired outcomes. A key strategy was the implementation of a nurse manager/attending physician dyad model. This partnership is the linkage from the front line to the institute chair. The focus on collegiality and collaboration has led to improved engagement and problem-solving within the service lines.


Assuntos
Unidades de Terapia Intensiva , Atenção à Saúde , Hospitais , Humanos , Corpo Clínico Hospitalar , Assistência Centrada no Paciente
9.
Crit Care Nurs Q ; 43(4): 468-479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833781

RESUMO

The COVID-19 pandemic presented an unprecedented opportunity to test the emergency management plan of one large urban teaching hospital. In this article, a detailed description of the hospital's surge planning process with lessons learned has been provided.


Assuntos
Infecções por Coronavirus/epidemiologia , Hospitais de Ensino/organização & administração , Hospitais Urbanos/organização & administração , Enfermeiros Administradores/psicologia , Pandemias , Pneumonia Viral/epidemiologia , Capacidade de Resposta ante Emergências/organização & administração , COVID-19 , Humanos , Pennsylvania/epidemiologia
10.
Vet Surg ; 48(3): 360-366, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30693966

RESUMO

OBJECTIVE: To determine students' stress while performing surgery and evaluate the ability of a mindfulness intervention to reduce this stress. STUDY DESIGN: Quasi-experimental design. SAMPLE POPULATION: Eighteen fourth-year DVM program students (n = 9 student/group). METHODS: Utilizing a quasi-experimental design, students were randomly assigned to a control or treatment group. The treatment group performed a 5-minute breathing (mindfulness) exercise immediately prior to performing surgery. Each student provided 3 samples of saliva, at time 0, at 10 minutes before surgery, and at 10 minutes after surgery. Students' salivary cortisol and α-amylase levels were compared between groups. Students' self-reported mood measures were also correlated to levels of salivary biomarkers. RESULTS: Cortisol and α-amylase levels of students in both groups greatly exceeded normative reference groups (>90th percentile) prior to surgery and diminished to average levels (50th-60th percentile) after surgery but did not differ between groups at any time point. Immediately prior to surgery when stress values were likely to peak, salivary α-amylase levels decreased approximately 30 U/L units for students in the treatment group compared with an increase of approximately 10 U/L units for students in the control group. Students in the treatment group reported being more calm (mean [M] 2.67, SD 1.03, d = 0.75) and relaxed (M 2.33, SD 1.51, d = 0.90) than students in the control group (M 3.44, SD 1.01 and M 3.44, SD 0.88, respectively). CONCLUSION: This study provides some evidence that the mindfulness intervention temporarily decreased stress levels and improved students' sense of calmness and relaxation immediately before operating on a live animal. CLINICAL IMPACT: Students who are experiencing less stress may be less likely to commit a medical error and negatively impact animal health. This study, the first of its kind in veterinary surgery, may serve as a model for related future studies.


Assuntos
Educação em Veterinária , Atenção Plena , Estresse Psicológico/prevenção & controle , Estudantes , Animais , Feminino , Humanos , Hidrocortisona/sangue , Masculino , alfa-Amilases/sangue
11.
R I Med J (2013) ; 100(10): 45-47, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28968623

RESUMO

New Rhode Island regulations require physicians and other licensed practitioners to make significant adjustments to comply with new requirements for prescribing narcotics for chronic pain. Responding to the opioid epidemic, the new rules are intended to improve patient safety by changing physicians' prescribing patterns. However, the new rules may overlook the importance of treatment-access problems and the importance of buprenorphine products for treating pain and opioid dependence. Empirical data have demonstrated the safety and efficacy of buprenorphine in treating opioid-dependent patients with chronic pain, including those with and without substance abuse histories, but access to buprenorphine treatment remains limited throughout the state. The new regulations call upon physicians to make use of consultation services, which are also of limited availability. Although well intentioned, the new rules may contribute to treatment-access problems, and patients with chronic pain may resort to higher-risk "street" drugs when they are unable to access safe but effective medical treatment. [Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Padrões de Prática Médica/legislação & jurisprudência , Buprenorfina/uso terapêutico , Centers for Disease Control and Prevention, U.S. , Política de Saúde , Humanos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Guias de Prática Clínica como Assunto , Rhode Island/epidemiologia , Estados Unidos/epidemiologia
12.
Mov Disord ; 30(9): 1248-58, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26148135

RESUMO

The basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits are important for motor control. Whether their functioning is affected in a similar or different way by progressive supranuclear palsy (PSP) and Parkinson's disease (PD) is not clear. A functional magnetic resonance imaging (fMRI) force production paradigm and voxel-based morphometry were used to assess differences in brain activity and macrostructural volumes between PSP, PD, and healthy age-matched controls. We found that PSP and PD share reduced functional activity of the basal ganglia and cortical motor areas, but this is more pronounced in PSP than in PD. In PSP the frontal regions are underactive, whereas the posterior parietal and occipital regions are overactive as compared with controls and PD. Furthermore, lobules I through IV, V, and VI of the cerebellum are hypoactive in PSP and PD, whereas Crus I and lobule IX are hyperactive in PSP only. Reductions in gray and white matter volume are specific to PSP. Finally, the functional status of the caudate as well as the volume of the superior frontal gyrus predict clinical gait and posture measures in PSP. PSP and PD share hypoactivity of the basal ganglia, motor cortex, and anterior cerebellum. These patients also display a unique pattern, such that anterior regions of the cortex are hypoactive and posterior regions of the cortex and cerebellum are hyperactive. Together, these findings suggest that specific structures within the basal ganglia, cortex, and cerebellum are affected differently in PSP relative to PD.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/patologia , Doença de Parkinson/patologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Análise de Variância , Feminino , Força da Mão/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Paralisia Supranuclear Progressiva/fisiopatologia
13.
Brain ; 138(Pt 8): 2322-31, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25981960

RESUMO

There is a clear need to develop non-invasive markers of substantia nigra progression in Parkinson's disease. We previously found elevated free-water levels in the substantia nigra for patients with Parkinson's disease compared with controls in single-site and multi-site cohorts. Here, we test the hypotheses that free-water levels in the substantia nigra of Parkinson's disease increase following 1 year of progression, and that baseline free-water levels in the substantia nigra predict the change in bradykinesia following 1 year. We conducted a longitudinal study in controls (n = 19) and patients with Parkinson's disease (n = 25). Diffusion imaging and clinical data were collected at baseline and after 1 year. Free-water analyses were performed on diffusion imaging data using blinded, hand-drawn regions of interest in the posterior substantia nigra. A group effect indicated free-water values were increased in the posterior substantia nigra of patients with Parkinson's disease compared with controls (P = 0.003) and we observed a significant group × time interaction (P < 0.05). Free-water values increased for the Parkinson's disease group after 1 year (P = 0.006), whereas control free-water values did not change. Baseline free-water values predicted the 1 year change in bradykinesia scores (r = 0.74, P < 0.001) and 1 year change in Montreal Cognitive Assessment scores (r = -0.44, P = 0.03). Free-water in the posterior substantia nigra is elevated in Parkinson's disease, increases with progression of Parkinson's disease, and predicts subsequent changes in bradykinesia and cognitive status over 1 year. These findings demonstrate that free-water provides a potential non-invasive progression marker of the substantia nigra.


Assuntos
Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Substância Negra/metabolismo , Substância Negra/patologia , Água/metabolismo , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia
14.
Front Hum Neurosci ; 9: 184, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25904859

RESUMO

Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes pure cerebellar degeneration affecting walking, balance, and coordination. One of the main symptoms of SCA6 is dysmetria. The magnitude of dysmetria and its relation to functional capacity in SCA6 has not been studied. Our purpose was to quantify dysmetria and determine the relation between dysmetria and functional capacity in SCA6. Ten individuals diagnosed and genetically confirmed with SCA6 (63.7 ± 7.02 years) and nine age-matched healthy controls (65.9 ± 8.5 years) performed goal-directed isometric contractions with the ankle joint. Dysmetria was quantified as the force and time error during goal-directed contractions. SCA6 functional capacity was determined by ICARS and SARA clinical assessments. We found that SCA6 participants exhibited greater force dysmetria than healthy controls (P < 0.05), and reduced time dysmetria than healthy controls (P < 0.05). Only force dysmetria was significantly related to SCA6 functional capacity, as measured with ICARS kinetic score (R(2) = 0.63), ICARS total score (R(2) = 0.43), and SARA total score (R(2) = 0.46). Our findings demonstrate that SCA6 exhibit force dysmetria and that force dysmetria is associated to SCA6 functional capacity. Quantifying force and time dysmetria in individuals with SCA6 could provide a more objective evaluation of the functional capacity and disease state in SCA6.

15.
Neurobiol Aging ; 36(2): 1097-104, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25467638

RESUMO

Measures from diffusion magnetic resonance imaging reflect changes in the substantia nigra of Parkinson's disease. It is the case, however, that partial volume effects from free water can bias diffusion measurements. The bi-tensor diffusion model was introduced to quantify the contribution of free water and eliminates its bias on estimations of tissue microstructure. Here, we test the hypothesis that free water is elevated in the substantia nigra for Parkinson's disease compared with control subjects. This hypothesis was tested between large cohorts of Parkinson's disease and control participants in a single-site study and validated against a multisite study using multiple scanners. The fractional volume of free water was increased in the posterior region of the substantia nigra in Parkinson's disease compared with control subjects in both the single-site and multi-site studies. We did not observe changes in either cohort for free-water-corrected fractional anisotropy or free-water-corrected mean diffusivity. Our findings provide new evidence that the free-water index reflects alteration of the substantia nigra in Parkinson's disease, and this was evidenced across both single-site and multi-site cohorts.


Assuntos
Água Corporal/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Substância Negra/metabolismo , Substância Negra/patologia , Idoso , Anisotropia , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
PLoS Pathog ; 3(6): e79, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17542646

RESUMO

Fitness is a parameter used to quantify how well an organism adapts to its environment; in the present study, fitness is a measure of how well strains of human immunodeficiency virus type 1 (HIV-1) replicate in tissue culture. When HIV-1 develops resistance in vitro or in vivo to antiretroviral drugs such as reverse transcriptase or protease inhibitors, its fitness is often impaired. Here, we have investigated whether the development of resistance in vitro to a small molecule CCR5 inhibitor, AD101, has an associated fitness cost. To do this, we developed a growth-competition assay involving dual infections with molecularly cloned viruses that are essentially isogenic outside the env genes under study. Real-time TaqMan quantitative PCR (QPCR) was used to quantify each competing virus individually via probes specific to different, phenotypically silent target sequences engineered within their vif genes. Head-to-head competition assays of env clones derived from the AD101 escape mutant isolate, the inhibitor-sensitive parental virus, and a passage control virus showed that AD101 resistance was not associated with a fitness loss. This observation is consistent with the retention of the resistant phenotype when the escape mutant was cultured for a total of 20 passages in the absence of the selecting compound. Amino acid substitutions in the V3 region of gp120 that confer complete AD101 resistance cause a fitness loss when introduced into an AD101-sensitive, parental clone; however, in the resistant isolate, changes elsewhere in env that occurred prior to the substitutions within V3 appear to compensate for the adverse effect of the V3 changes on replicative capacity. These in vitro studies may have implications for the development and management of resistance to other CCR5 inhibitors that are being evaluated clinically for the treatment of HIV-1 infection.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Fármacos Anti-HIV/farmacologia , Antagonistas dos Receptores CCR5 , Farmacorresistência Viral/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Niacinamida/análogos & derivados , Piperazinas/farmacologia , Adaptação Fisiológica/genética , Sequência de Bases , Células Cultivadas , Farmacorresistência Viral/genética , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Leucócitos Mononucleares/virologia , Dados de Sequência Molecular , Niacinamida/farmacologia , Receptores CCR5/metabolismo , Replicação Viral/efeitos dos fármacos
17.
Virology ; 321(1): 8-22, 2004 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-15033560

RESUMO

Primary strains of human immunodeficiency virus type 1 (HIV-1) are known to adapt to replication in cell lines in vitro by becoming sensitive to soluble CD4 (sCD4) and neutralizing antibodies (NAb). T-cell lines favor isolation of variants that use CXCR4 as a co-receptor, while primary isolates predominantly use CCR5. We have now studied how a primary R5 isolate, CC1/85, adapts to prolonged replication in primary human peripheral blood mononuclear cells (PBMC). After 19 passages, a variant virus, CCcon.19, had increased sensitivity to both sCD4 and NAb b12 that binds to a CD4-binding site (CD4BS)-associated epitope, but decreased sensitivity to anti-CD4 antibodies. CCcon.19 retains the R5 phenotype, its resistance to other NAbs was unaltered, its sensitivity to various entry inhibitors was unchanged, and its ability to replicate in macrophages was modestly increased. We define CCcon.19 as a primary T-cell adapted (PTCA) variant. Genetic sequence analysis combined with mutagenesis studies on clonal, chimeric viruses derived from CC1/85 and the PTCA variant showed that the most important changes were in the V1/V2 loop structure, one of them involving the loss of an N-linked glycosylation site. Monomeric gp120 proteins expressed from CC1/85 and the PTCA variant did not differ in their affinities for sCD4, suggesting that the structural consequences of the sequence changes were manifested at the level of the native, trimeric Env complex. Overall, the adaptation process probably involves selection for variants with higher CD4 affinity and hence greater fusion efficiency, but this also involves the loss of some resistance to neutralization by agents directed at or near to the CD4BS. The loss of neutralization resistance is of no relevance under in vitro conditions, but NAbs would presumably be a counter-selection pressure against such adaptive changes in vivo, at least when the humoral immune response is intact.


Assuntos
Antígenos CD4/imunologia , HIV-1/imunologia , Leucócitos Mononucleares/virologia , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Sítios de Ligação , Antagonistas dos Receptores CCR5 , Antígenos CD4/química , Antígenos CD4/farmacologia , Células Cultivadas , Sequência Consenso , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Dados de Sequência Molecular , Testes de Neutralização , Receptores CCR5/genética , Solubilidade , Replicação Viral
18.
J Virol ; 78(6): 2790-807, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14990699

RESUMO

We have described previously the generation of an escape variant of human immunodeficiency virus type 1 (HIV-1), under the selection pressure of AD101, a small molecule inhibitor that binds the CCR5 coreceptor (A. Trkola, S. E. Kuhmann, J. M. Strizki, E. Maxwell, T. Ketas, T. Morgan, P. Pugach, S. X. L. Wojcik, J. Tagat, A. Palani, S. Shapiro, J. W. Clader, S. McCombie, G. R. Reyes, B. M. Baroudy, and J. P. Moore, Proc. Natl. Acad. Sci. USA 99:395-400, 2002). The escape mutant, CC101.19, continued to use CCR5 for entry, but it was at least 20,000-fold more resistant to AD101 than the parental virus, CC1/85. We have now cloned the env genes from the the parental and escape mutant isolates and made chimeric infectious molecular clones that fully recapitulate the phenotypes of the corresponding isolates. Sequence analysis of the evolution of the escape mutants suggested that the most relevant changes were likely to be in the V3 loop of the gp120 glycoprotein. We therefore made a series of mutant viruses and found that full AD101 resistance was conferred by four amino acid changes in V3. Each change individually caused partial resistance when they were introduced into the V3 loop of a CC1/85 clone, but their impact was dependent on the gp120 context in which they were made. We assume that these amino acid changes alter how the HIV-1 Env complex interacts with CCR5. Perhaps unexpectedly, given the complete dependence of the escape mutant on CCR5 for entry, monomeric gp120 proteins expressed from clones of the fully resistant isolate failed to bind to CCR5 on the surface of L1.2-CCR5 cells under conditions where gp120 proteins from the parental virus and a partially AD101-resistant virus bound strongly. Hence, the full impact of the V3 substitutions may only be apparent at the level of the native Env complex.


Assuntos
Fármacos Anti-HIV/farmacologia , Antagonistas dos Receptores CCR5 , Farmacorresistência Viral , HIV-1/efeitos dos fármacos , HIV-1/genética , Sequência de Aminoácidos , Genótipo , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Proteína gp160 do Envelope de HIV/química , Proteína gp160 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/metabolismo , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fenótipo , Receptores CCR5/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência
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