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1.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34379922

RESUMO

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Assuntos
Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto Jovem
2.
J Infect Dis ; 225(10): 1741-1749, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35301540

RESUMO

BACKGROUND: HIV Prevention Trials Network 084 demonstrated that long-acting injectable cabotegravir (CAB) was superior to daily oral tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) for preventing human immunodeficiency virus (HIV) infection in sub-Saharan African women. This report describes HIV infections that occurred in the trial before unblinding. METHODS: Testing was performed using HIV diagnostic assays, viral load testing, a single-copy RNA assay, and HIV genotyping. Plasma CAB, plasma TFV, and intraerythrocytic TFV-diphosphate concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Forty HIV infections were identified (CAB arm, 1 baseline infection, 3 incident infections; TDF/FTC arm, 36 incident infections). The incident infections in the CAB arm included 2 with no recent drug exposure and no CAB injections and 1 with delayed injections; in 35 of 36 cases in the TDF/FTC arm, drug concentrations indicated low or no adherence. None of the cases had CAB resistance. Nine women in the TDF/FTC arm had nonnucleoside reverse-transcriptase inhibitor resistance; 1 had the nucleoside reverse-transcriptase inhibitor resistance mutation, M184V. CONCLUSIONS: Almost all incident HIV infections occurred in the setting of unquantifiable or low drug concentrations. CAB resistance was not detected. Transmitted nonnucleoside reverse-transcriptase inhibitor resistance was common; 1 woman may have acquired nucleoside reverse-transcriptase inhibitor resistance from study drug exposure.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Fármacos Anti-HIV/uso terapêutico , RNA Polimerases Dirigidas por DNA , Dicetopiperazinas , Emtricitabina/uso terapêutico , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Nucleosídeos/uso terapêutico , Piridonas , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico
3.
J Manipulative Physiol Ther ; 45(3): 216-226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35906104

RESUMO

OBJECTIVE: The purpose of this study was to examine the effects of submaximal isometric neck muscle fatigue and manual therapy on wrist joint position sense (JPS) within healthy individuals and individuals with subclinical neck pain (SCNP). METHODS: Twelve healthy participants and 12 participants with SCNP were recruited. Each group completed 2 sessions, with 48 hours between sessions. On day 1, both groups performed 2 wrist JPS tests using a robotic device. The tests were separated by a submaximal isometric fatigue protocol for the cervical extensor muscles (CEM). On day 2, both groups performed a wrist JPS test, followed by a cervical treatment consisting of manual therapy (SCNP) or neck rest (20 minutes, control group) and another wrist JPS test. Joint position sense was measured as the participant's ability to recreate a previously presented wrist angle. Each wrist JPS test included 12 targets, 6 into wrist flexion and 6 into wrist extension. Kinematic data from the robot established absolute, variability, and constant error. RESULTS: Absolute error significantly decreased (P = .01) from baseline to post-fatigue in the SCNP group (baseline = 4.48 ± 1.58°; post-fatigue = 3.90 ± 1.45°) and increased in the control group (baseline = 3.12 ± 0.98°; post-fatigue = 3.81 ± 0.90°). The single session of manual cervical treatment significantly decreased absolute error in participants with SCNP (P = .004). CONCLUSION: This study demonstrated that neck pain or fatigue can lead to altered afferent input to the central nervous system and can affect wrist JPS. Our findings demonstrate that acute wrist proprioception may be improved in individuals with SCNP by a single cervical manual therapy session.


Assuntos
Fadiga Muscular , Manipulações Musculoesqueléticas , Humanos , Fadiga Muscular/fisiologia , Cervicalgia/terapia , Propriocepção/fisiologia , Punho , Articulação do Punho
4.
J Clin Microbiol ; 59(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33139419

RESUMO

Accurate serological assays to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donation. This study compared the performances of commercial enzyme immunoassays (EIAs) with respect to detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 was evaluated using cross-sectional samples from potential CCP donors who had prior molecular confirmation of SARS-CoV-2 infection (n = 214) and samples from prepandemic emergency department patients without SARS-CoV-2 infection (n = 1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority (n = 16 [7.5%]) had been hospitalized due to COVID-19; 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. Performed according to the protocols of the manufacturers to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff value of ≥160 as the reference representing a positive test result (n = 140 CCP donors), the empirical area under the receiver operating curve for each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAb titers. Some but not all commercial EIAs may be useful in the identification of individuals with high nAb titers among convalescent individuals.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , COVID-19/sangue , Estudos Transversais , Humanos , Soros Imunes/imunologia , Técnicas Imunoenzimáticas , Imunoglobulina G/sangue , Testes de Neutralização , SARS-CoV-2/imunologia , Sensibilidade e Especificidade
5.
J Clin Periodontol ; 45(5): 578-585, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29500837

RESUMO

AIMS: To determine the relationship between anticipated pain and actual pain experienced following soft tissue grafting or implant surgery; to identify the factors that predict actual pain experienced and the use of pain medication following soft tissue grafting or implant surgery. MATERIALS AND METHODS: Prior to dental implant placement (n = 98) or soft tissue grafting (n = 115) and for seven days following the procedure, patients completed a visual analog scale indicating anticipated or experienced pain, respectively. The use of pain medication and alcohol, and smoking were measured. RESULTS: Actual pain experienced on day 1 was lower (p < .01) than anticipated pain and continued to decrease (p ≤ .01) for each of the 7 consecutive days. Anticipated and actual pain were positively correlated. Increasing age (p < .05), having sedation during the surgery (p < .05), and lower use of pain pills (p < .01) predicted lower pain experienced. Actual pain experienced was a predictor of pain pill use (p < .01). Greater nervousness (p < .01) prior to surgery was a predictor of greater anticipated pain. CONCLUSIONS: Patients anticipated more pain than they actually experienced. Sedation, age and number of pain pills used predicted pain experienced. This trial was registered with clinicaltrials.gov as NCT03064178.


Assuntos
Medo , Procedimentos Cirúrgicos Bucais , Medição da Dor , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Doenças Periodontais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Implantes Dentários , Feminino , Gengiva/transplante , Humanos , Masculino , Pessoa de Meia-Idade
6.
Subst Use Misuse ; 52(8): 1098-1103, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28429996

RESUMO

BACKGROUND: The coaching process is complex and dynamic. Coaches are known to affect athlete attitudes indirectly, through athletes' perceptions and interpretations. This process has been verified with a variety of ethical behaviors. OBJECTIVES: The current study investigated the relationships between athletes' perceived doping confrontation efficacy of their coaches and athlete's anti-doping attitudes. METHODS: A sample of athletes (N = 96) completed a version of the Doping Confrontation Efficacy Scale that was modified to assess their perception of their coaches' anti-doping confrontation efficacy, and the PEAS (Performance Enhancing Attitude Scale), which assessed their performance-enhancing attitudes. RESULTS: The results of a multiple linear regression model showed that perceived confrontation efficacy significantly predicted athletes' anti-doping attitudes. Specifically, the factor of efficacy with respect to intimacy was the sole significant predictor. CONCLUSIONS: These results show that a pattern of athletes' interpretation of coaches' values is related to their own attitudes, much like with cheating and sportsmanship. This finding is consistent with the conceptualization of confrontation in general independent of sport.


Assuntos
Atletas/psicologia , Atitude , Dopagem Esportivo/psicologia , Percepção , Adolescente , Adulto , Feminino , Humanos , Masculino , Princípios Morais , Adulto Jovem
7.
J Sport Exerc Psychol ; 39(4): 261-276, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29084461

RESUMO

Coaching efficacy refers to the extent to which a coach believes that he or she has the capacity to affect the learning and performance of his or her athletes. The purpose of the current study was to empirically synthesize findings across the extant literature to estimate relationships between the proposed sources of coaching efficacy and each of the dimensions of coaching efficacy. A literature search yielded 20 studies and 278 effect size estimates that met the inclusion criteria. The overall relationship between the proposed sources of coaching efficacy and each dimension of coaching efficacy was positive and ranged from small to medium in size. Coach gender and level coached moderated the overall relationship between the proposed sources of coaching efficacy and each of the dimensions of coaching efficacy. Results from this meta-analysis provided some evidence for both the utility of, and possible revisions to, the conceptual model of coaching efficacy.


Assuntos
Tutoria , Educação Física e Treinamento , Competência Profissional , Esportes/psicologia , Humanos , Relações Interpessoais , Modelos Psicológicos
8.
Am J Psychol ; 129(1): 81-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27029108

RESUMO

We investigated the mediating role of body shame in the relationship between self-objectification and body image coping strategies in highly physically active university women. Bivariate correlations revealed body shame was positively related to self-objectification, appearance fixing, and avoidance coping but unrelated to positive rational acceptance. In addition, self-objectification was positively related to appearance fixing and avoidance coping but unrelated to positive rational acceptance. Mediation analyses showed that body shame partially mediated the relationship between self-objectification and avoidance and appearance fixing coping but did not mediate the relationship between self-objectification and positive rational acceptance. Future research should examine other potential mediators or moderators in this relationship and explore the role of positive body image framed within self-objectification theory.


Assuntos
Adaptação Psicológica/fisiologia , Imagem Corporal/psicologia , Vergonha , Adulto , Feminino , Humanos , Atividade Motora/fisiologia , Adulto Jovem
9.
J Nutr ; 145(11): 2512-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26423734

RESUMO

BACKGROUND: Periodontitis is a chronic inflammatory disease and a significant risk factor for tooth loss. Although a link between diet and periodontal health exists, the relation between diet and healing after periodontal therapy has yet to be investigated. OBJECTIVE: The objective was to determine whether higher intakes of fruits and vegetables or nutrients with antioxidant or anti-inflammatory activity are associated with greater healing, measured as reduced probing depth (PD), after scaling and root planing (SRP), a cost-effective treatment to manage periodontal disease and prevent tooth loss. METHODS: Patients (63 nonsmokers, 23 smokers) with chronic generalized periodontitis who were undergoing SRP participated. Healing was evaluated based on PD, assessed at baseline and 8-16 wk after SRP. Intakes of fruits, vegetables, ß-carotene, vitamin C, α-tocopherol, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were estimated using the Block 2005 food frequency questionnaire and a supplement questionnaire. Serum 25-hydroxyvitamin D concentrations were also measured. PD (% sites >3 mm) was modeled in multiple linear regression and analysis of covariance by tertile of intake and adjusted for age, sex, body mass index (BMI), baseline PD, examiner, gingival bleeding, and study duration. RESULTS: In nonsmokers, PD was associated with fruit and vegetable, ß-carotene, vitamin C, α-tocopherol, EPA, and DHA intakes (P < 0.05). PD was not significantly associated with ALA intake or serum 25-hydroxyvitamin D concentration. Significant associations that included supplements (ß-carotene, vitamin C, α-tocopherol) were attenuated or lost, depending on the statistical model used. There were no significant associations within the group of smokers. CONCLUSIONS: Dietary intakes of fruits and vegetables, ß-carotene, vitamin C, α-tocopherol, EPA, and DHA are associated with reduced PD after SRP in nonsmokers, but not smokers, with chronic generalized periodontitis. These findings may lead to the development of dietary strategies to optimize healing after periodontal procedures. This trial was registered at clinicaltrials.gov as NCT02291835.


Assuntos
Ácido Ascórbico/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Periodontite/terapia , Fumar/efeitos adversos , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/administração & dosagem , Índice de Massa Corporal , Doença Crônica , Estudos Transversais , Suplementos Nutricionais , Ingestão de Energia , Feminino , Frutas , Humanos , Inflamação/tratamento farmacológico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Inquéritos e Questionários , Verduras , Vitamina D/análogos & derivados , Vitamina D/sangue , Ácido alfa-Linolênico/administração & dosagem
10.
Lancet HIV ; 10(12): e767-e778, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37952550

RESUMO

BACKGROUND: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study. METHODS: The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094. FINDINGS: Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation. INTERPRETATION: Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.


Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Profilaxia Pré-Exposição , Pessoas Transgênero , Masculino , Feminino , Humanos , Adolescente , Infecções por HIV/tratamento farmacológico , Tenofovir/efeitos adversos , Emtricitabina/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Estudos Retrospectivos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico
11.
Lancet HIV ; 10(11): e703-e712, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37783219

RESUMO

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083. METHODS: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094. FINDINGS: HPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use. INTERPRETATION: HIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women. FUNDING: National Institute of Allergy and Infectious Diseases and ViiV Healthcare.


Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Profilaxia Pré-Exposição , Pessoas Transgênero , Feminino , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hormônios/uso terapêutico , Profilaxia Pré-Exposição/métodos , Tenofovir/uso terapêutico , Tailândia
12.
Langmuir ; 28(6): 3338-44, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22220731

RESUMO

Silicon photonic microring resonators have established their potential for label-free and low-cost biosensing applications. However, the long-term performance of this optical sensing platform requires robust surface modification and biofunctionalization. Herein, we demonstrate a conjugation strategy based on an organophosphonate surface coating and vinyl sulfone linker to biofunctionalize silicon resonators for biomolecular sensing. To validate this method, a series of glycans, including carbohydrates and glycoconjugates, were immobilized on divinyl sulfone (DVS)/organophosphonate-modified microrings and used to characterize carbohydrate-protein and norovirus particle interactions. This biofunctional platform was able to orthogonally detect multiple specific carbohydrate-protein interactions simultaneously. Additionally, the platform was capable of reproducible binding after multiple regenerations by high-salt, high-pH, or low-pH solutions and after 1 month storage in ambient conditions. This remarkable stability and durability of the organophosphonate immobilization strategy will facilitate the application of silicon microring resonators in various sensing conditions, prolong their lifetime, and minimize the cost for storage and delivery; these characteristics are requisite for developing biosensors for point-of-care and distributed diagnostics and other biomedical applications. In addition, the platform demonstrated its ability to characterize carbohydrate-mediated host-virus interactions, providing a facile method for discovering new antiviral agents to prevent infectious disease.


Assuntos
Técnicas Biossensoriais , Organofosfatos/química , Silício/química , Concentração de Íons de Hidrogênio , Modelos Teóricos , Sulfonas/química
13.
Acc Chem Res ; 43(1): 10-8, 2010 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-19663413

RESUMO

Correlated time-dependent density functional theory (TDDFT) quantum mechanical and pseudo-atomistic Monte Carlo (PAMC) statistical mechanical methods have been used to assist in the understanding of and to guide the improvement of organic electro-optic (OEO) materials, prepared by electric field poling of pi-electron chromophore-containing materials near their glass transition temperature. Theoretical treatment of the effects of dielectric permittivity and optical frequency on molecular (chromophore) first hyperpolarizabilities has been carried out as well as the analysis of the influence of spatially anisotropic intermolecular electrostatic interactions on the poling-induced noncentrosymmetric order of chromophores. Three classes of OEO materials have been considered in correlated theoretical and experimental investigations: (1) traditional chromophore/polymer composite materials, (2) chromophores covalently incorporated into polymers, dendrimers, and dendronized polymers, and (3) recently discovered materials consisting of chromophores incorporated into chromophore-containing host materials. This latter class of materials is referred to as binary chromophore organic glasses (BCOGs). These BCOGs exhibit exceptional electro-optic activity because of a combination of high chromophore number density, the effect of high dielectric permittivity on molecular first hyperpolarizability, and improved acentric order arising from the intermolecular electrostatic interactions among the two types of chromophores. The electrical conductivity of materials can also influence achievable electro-optic activity, and thin metal oxide buffer layers, introduced to limit charge injection, can significantly improve poling efficiency. Chromophore order can also be influenced, in some cases, by novel processing techniques, such as laser-assisted electric field poling. Thermal and photostability are important parameters for practical application of materials and have been improved dramatically in recent times. Diels-Alder and fluorovinyl ether cycloaddition reactions have been used to elevate final material glass transition temperatures to above 200 degrees C. Photostability is dominated by the photoactivation of singlet oxygen and subsequent attack on electro-optic chromophores. Photostability can be improved by more than 4 orders of magnitude by chromophore modification and material packaging.

14.
Clin Exp Dent Res ; 7(5): 647-655, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33474841

RESUMO

OBJECTIVE: Non-surgical scaling and root planing (SRP), as an initial form of periodontal treatment, followed by ongoing periodontal maintenance appointments is necessary to manage periodontal disease and prevent tooth loss. Saliva also has an essential role in oral health though the relationship between low salivary flow and periodontal outcomes has not been extensively investigated. This study determined if patients with dry mouth have similar clinical outcomes as patients without dry mouth when receiving regular periodontal maintenance after SRP. MATERIALS AND METHODS: This is a retrospective study that investigated clinical periodontal outcomes in patients with (n = 34) or without (n = 85) dry mouth who had undergone SRP 1 to 5 years prior and had routine periodontal maintenance. The presence of dry mouth was established based on a patient's unstimulated salivary flow rate. RESULTS: Probing depth for both patients with or without dry mouth was similar between groups and maintained 1 to 5 years following initial SRP. Improved probing depth achieved post-SRP was sustained regardless of dry mouth status. CONCLUSION: Patients with or without dry mouth did not exhibit different probing depths.


Assuntos
Doenças Periodontais , Xerostomia , Raspagem Dentária , Humanos , Doenças Periodontais/complicações , Doenças Periodontais/terapia , Estudos Retrospectivos , Aplainamento Radicular , Xerostomia/etiologia , Xerostomia/terapia
15.
Clin Exp Dent Res ; 7(1): 123-128, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32954684

RESUMO

OBJECTIVE: Diet and dietary supplement use are associated with periodontal health while a cause and effect relationship is less clear. Although associations with specific nutrients and supplements suggest a potential benefit to healing of periodontal tissues after periodontal procedures, this study determined if patients undergoing periodontal surgery currently take dietary supplements to gage whether patients may accept use of such supplements as a potential intervention. MATERIALS AND METHODS: Patients who were undergoing implant placement or soft tissue graft surgery completed a questionnaire indicating any dietary supplements they consumed. Patient demographics, such as age, sex, and smoking status, were gathered from patients' charting records. RESULTS: Data on dietary supplement usage were collected from 221 patients. More than half (64.7%) the population surveyed reported using one or more dietary supplements. The most commonly used dietary supplements were vitamin D (31%), multivitamin (28%), and B-complex (17.2%). Females were more likely to be taking calcium, vitamin B12, and magnesium than males. Adults, aged 51 years and older, were more likely to be taking dietary supplements than their younger counterparts. They were also more likely to be taking four or more supplements than those under the age of 50 years. There was no association between supplement use and sex, but when the number of different supplements being used was assessed, females were more likely than males to be taking four or more different supplements. CONCLUSIONS: The majority of the study population is already taking dietary supplements as part of their routine. Based on this study, future studies to determine if supplement usage, potentially at levels higher than current levels of intake, can be used to maintain or promote periodontal health seem highly feasible.


Assuntos
Suplementos Nutricionais , Periodontia , Vitaminas , Adulto , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Projetos de Pesquisa
16.
Pediatr Obes ; 15(12): e12690, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32602233

RESUMO

BACKGROUND: Exercise can improve body composition in adolescents and adults with overweight/obesity. Consumption of dairy foods, as part of a healthy lifestyle program, can also promote favourable body composition changes in adults with overweight/obesity. However, the few studies examining these combined effects on body composition in adolescents are inconclusive. OBJECTIVE: To determine whether increased dairy product consumption, as part of a lifestyle modification program featuring exercise training and dietary guidance promotes favourable body composition changes in adolescent females with overweight/obesity. METHODS: Fifty-four participants (age: 14.8 ± 2.2y; BMI percentile: 95th ± 6) assigned to three groups completed the study. There were two experimental groups: recommended dairy (RDa; n = 24) and low dairy (LDa; n = 22), and a no-intervention control group (Con; n = 8). RDa and LDa participated in a 12-week, eucaloric, lifestyle modification intervention consisting of mixed-mode exercise (3x/week), and nutritional counselling. RDa was provided 4 servings/day of dairy foods, while LDa and Con maintained habitually low intakes (0-2 servings/day). Body weight/composition, waist/hip circumference, cardiovascular fitness and food intake were assessed at weeks 0 and 12. RESULTS: Weight did not significantly change in any group. RDa significantly decreased fat mass (FM) and increased lean mass (LM) more than LDa and Con (FM: -1.3 ± 2.1 kg, -1.1 ± 2.0 kg, 0.8 ± 1.8 kg; LM: 1.5 ± 1.9 kg, 0.7 ± 1.6 kg, 0.5 ± 1.4 kg, respectively). LDa also significantly decreased FM and increased LM more than Con (P < .005; all interactions). CONCLUSION: The inclusion of dairy foods in the diet of adolescent females with overweight/obesity, as part of a diet and exercise intervention, favourably improves body composition in the absence of weight loss.


Assuntos
Composição Corporal , Laticínios , Exercício Físico , Sobrepeso/terapia , Obesidade Infantil/terapia , Programas de Redução de Peso , Adolescente , Dieta , Feminino , Humanos
17.
J Int AIDS Soc ; 23(2): e25452, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32072743

RESUMO

INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.


Assuntos
Sorodiagnóstico da AIDS/métodos , Algoritmos , Infecções por HIV/diagnóstico , Adulto , Confiabilidade dos Dados , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Incidência , Masculino , Programas de Rastreamento , Ensaios Clínicos Controlados Aleatórios como Assunto , África do Sul/epidemiologia , Zâmbia/epidemiologia
18.
medRxiv ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32908987

RESUMO

Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection for sensitivity (n=214) and pre-pandemic emergency department patients for specificity (n=1,102). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.

19.
Bone Rep ; 10: 100191, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30656199

RESUMO

BACKGROUND: Calcium (Ca) and vitamin D (vit D) in the AIN-93G diet may be higher than required for healthy bone development, and mask the potential benefit of a dietary intervention. OBJECTIVE: The objective was to determine if lower levels of Ca and vit D than is present in the AIN-93G diet supports bone development in growing male CD-1 mice. METHODS: Weanling male CD-1 mice were randomized to modified AIN-93G diets containing either 100 (Trial 1) or 400 (Trial 2) IU vit D/kg diet within one of two or three Ca levels (0.35, 0.30, or 0.25% Ca diet in Trial 1 or 0.35% or 0.25% in Trial 2) or the AIN-93G diet (1000 IU/kg vit D and 0.5% Ca) from weaning to 4 months of age (n = 13-15/group). At 2 and 4 months of age, BMD and structural properties of the tibia were analyzed in vivo. Structure of lumbar vertebra 4 (L4) and mandible, and femur strength were assessed ex vivo at age 4 months. RESULTS: There were no differences in tibia, L4, and mandible structure between the AIN-93G diet and the 0.35% Ca groups at either vit D level. A few structure outcomes were compromised with the 0.25 and/or 0.3% Ca diets but there were no differences in femur biomechanical strength compared to AIN-93G group in either Trial. CONCLUSION: At 400 or 100 IU vit D/kg diet, Ca can be lowered to 0.35% without detriment to BMD or bone structure while bone strength is not altered at lower Ca (0.25%) compared to CD-1 mice fed AIN-93G diet. Because of genetic variation in CD-1 mice among different breeding facilities, results in CD-1 mice from other facilities may differ from the present study.

20.
J Am Chem Soc ; 130(32): 10565-75, 2008 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-18642806

RESUMO

Two new highly hyperpolarizable chromophores, based on N,N- bis-(4-methoxyphenyl) aryl-amino donors and phenyl-trifluoromethyl-tricyanofuran (CF3-Ph-TCF) acceptor linked together via pi-conjugation through 2,5-divinylenethienyl moieties as the bridge, have been designed and synthesized successfully for the first time. The aryl moieties on the donor side of the chromophore molecules were varied as to be thiophene and 1-n-hexylpyrrole. The linear and nonlinear optical (NLO) properties of all compounds were evaluated in addition to recording relevant thermal and electrochemical data. The properties of the two new molecules were comparatively studied. These results are critically analyzed along with two other compounds, reported earlier from our laboratories and our collaborator's, that contain (i) aliphatic chain-bearing aniline and (ii) dianisylaniline as donors, keeping the bridge (2,5-divinylenethienyl-), and the acceptor (CF3-Ph-TCF), constant. Trends in theoretically (density functional theory, DFT) predicted, zero-frequency gas-phase hyperpolarizability [beta(0;0,0)] values are shown to be consistent with the trends in beta HRS(-2omega;omega,omega), as measured by Hyper-Rayleigh Scattering (HRS), when corrected to zero-frequency using the two-level model (TLM) approximation. Similarly, trends in poling efficiency data (r33/E(p)) and wavelength dispersion measured by reflection ellipsometry (using a Teng-Man apparatus) and attenuated total reflection (ATR) are found to fit the TLM and DFT predictions. A 3-fold enhancement in bulk nonlinearity (r33) is realized as the donor subunits are changed from alkylaniline to dianisylaminopyrrole donors. The results of these studies provide insight into the complicated effects on molecular hyperpolarizability of substituting heteroaromatic subunits into the donor group structures. These studies also demonstrate that, when frequency dependence and electric-field-induced ordering behavior are correctly accounted for, ab initio DFT generated beta(0;0,0) is effective as a predictor of changes in r33 behavior based on chromophore structure modification. Thus DFT can provide valuable insight into the electronic structure origin of complex optical phenomena in organic media.

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