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1.
Interact J Med Res ; 12: e41574, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37585242

RESUMO

BACKGROUND: The HIV epidemic remains a major public health concern, particularly among youths living with HIV. While the availability of antiretroviral therapy has significantly improved the health outcomes of people living with HIV, there is growing evidence that youths living with HIV may be at increased risk of cardiovascular disease. However, the underlying mechanisms linking HIV and cardiovascular disease among youths living with HIV remain poorly understood. One potential explanation is that HIV-related biomarkers, including detectable viral load (VL) and low cluster of differentiation 4 (CD4) lymphocyte counts, may contribute to increased cardiovascular risk. Despite the potential importance of these biomarkers, the relationship between HIV-related biomarkers and cardiovascular risk among youths living with HIV has been understudied. OBJECTIVE: To address this gap, we examined whether detectable VL and low CD4 lymphocyte counts, both of which are indications of unsuppressed HIV, were associated with cardiovascular risk among youths living with HIV. METHODS: We analyzed electronic health record data from 7 adolescent HIV clinics in the United States (813 youths living with HIV). We used multivariable linear regression to examine the relationship between detectable VL and CD4 lymphocyte counts of ≤200 and cardiovascular risk scores, which were adapted from the gender-specific Framingham algorithm. RESULTS: In our study, nearly half of the participants (366/766, 47.8%) had detectable VL, indicating unsuppressed HIV, while 8.6% (51/593) of them had CD4 lymphocyte counts of ≤200, suggesting weakened immune function. We found that those with CD4 lymphocyte counts of ≤200 had significantly higher cardiovascular risk, as assessed by Cardiac Risk Score2, than those with CD4 lymphocyte counts of >200 (P=.002). After adjusting for demographic and clinical factors, we found that for every 1000-point increase in VL copies/mL, the probability of having cardiovascular risk (Cardiac Risk Score2) increased by 38%. When measuring the strength of this connection, we observed a minor effect of VL on increased cardiovascular risk (ß=.134, SE 0.014; P=.006). We obtained similar results with Cardiac Risk Score1, but the effect of CD4 lymphocyte counts of ≤200 was no longer significant. Overall, our findings suggest that detectable VL is associated with increased cardiovascular risk among youths living with HIV, and that CD4 lymphocyte counts may play a role in this relationship as well. CONCLUSIONS: Our study highlights a significant association between unsuppressed HIV, indicated by detectable VL, and increased cardiovascular risk in youths living with HIV. These findings emphasize the importance of implementing interventions that address both VL suppression and cardiovascular risk reduction in this population. By tailoring interventions to meet the unique needs of youths, we can promote overall well-being throughout the HIV care continuum and across the life span. Ultimately, these efforts have the potential to improve the health outcomes and quality of life of youths living with HIV. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11185.

2.
J Chem Inf Model ; 63(13): 4070-4078, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37350740

RESUMO

DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4DCAF1 and the HECT family EDVPDCAF1 E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a binding platform for substrate proteins and is also targeted by HIV and SIV lentiviral adaptors to induce the ubiquitination and proteasomal degradation of antiviral host factors. It is therefore attractive both as a potential therapeutic target for the development of chemical inhibitors and as an E3 ligase that could be recruited by novel PROTACs for targeted protein degradation. In this study, we used a proteome-scale drug-target interaction prediction model, MatchMaker, combined with cheminformatics filtering and docking to identify ligands for the DCAF1 WDR domain. Biophysical screening and X-ray crystallographic studies of the predicted binders confirmed a selective ligand occupying the central cavity of the WDR domain. This study shows that artificial intelligence-enabled virtual screening methods can successfully be applied in the absence of previously known ligands.


Assuntos
Inteligência Artificial , Proteínas de Transporte , Ligantes , Proteínas de Transporte/química , Ubiquitina-Proteína Ligases/metabolismo , Aprendizado de Máquina
3.
JMIR Form Res ; 7: e40077, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36745773

RESUMO

BACKGROUND: Digital strategies and broadened eligibility criteria may optimize the enrollment of youth living with HIV in mobile health adaptive interventions. Prior research suggests that digital recruitment strategies are more efficient than traditional methods for overcoming enrollment challenges of youth living with HIV in the United States. OBJECTIVE: This study highlights the challenges and strategies that explain screening and enrollment milestones in a national web-based adherence protocol for youth living with HIV. METHODS: Baseline data from a national web-based HIV adherence protocol for youth living with HIV, collected from July 2018 to February 2021, were analyzed. A centralized recruitment procedure was developed, which used web-based recruitment via Online Master Screener; paid targeted advertisements on social media platforms (eg, Facebook and Reddit) and geosocial networking dating apps (eg, Grindr and Jack'd); and site and provider referrals from Subject Recruitment Venues and other AIDS service organizations, website referrals, and text-in recruitment. RESULTS: A total of 3 distinct cohorts of youth living with HIV were identified, marked by changes in recruitment strategies. Overall, 3270 individuals consented to screening, 2721 completed screening, 581 were eligible, and 83 completed enrollment. We examined sociodemographic and behavioral differences in completing milestones from eligibility to full enrollment (ie, submitting antiretroviral therapy and viral load data and completing the baseline web-based survey). Those with the most recent viral load tests >6 months ago were half as likely to enroll (odds ratio 0.45, 95% CI 0.21-0.94). Moreover, eligible participants with self-reported antiretroviral therapy adherence (SRA) between 50% and 80% were statistically significant (P<.001 to P=.03) and more likely to enroll than those with SRA >80%. CONCLUSIONS: The findings add to our knowledge on the use of digital technologies for youth living with HIV before and during the COVID-19 pandemic and provide insight into the impact of expanding eligibility criteria on enrollment. As the COVID-19 pandemic continues and the use of and engagement with social media and dating apps among youth living with HIV changes, these platforms should continue to be investigated as potential recruitment tools. Using a wide variety of recruitment strategies such as using social media and dating apps as well as provider referral mechanisms, increasing compensation amounts, and including SRA in enrollment criteria should continue to be studied with respect to their ability to successfully recruit and enroll eligible participants. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11183.

4.
Int J Mol Sci ; 24(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36768590

RESUMO

The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evaluating their potential anti-inflammatory activity. Fourteen chemical derivatives of carvone were synthesized, purified and their chemical structures confirmed. Noncytotoxic concentrations of the test compounds were selected based on the resazurin reduction assay. Among the tested compounds, four significantly reduced the lipopolysaccharides-induced protein levels of the inducible isoform of the nitric oxide synthase and nitric oxide production and showed a dual effect on pro-IL-1 protein levels in the Raw 264.7 cell line. The Ligand Express drug discovery platform was used to predict the targets of the test compounds, and an enrichment analysis was performed to group the different biological processes and molecular and cellular functions of the tested compounds. Moreover, Ligand Express also predicted that all chemicals evaluated have intestinal and blood-brain barrier permeability, do not inhibit P-gp and do not interact with major receptors. Although presenting anti-inflammatory and some advantageous ADME properties, the tested compounds still have low potency and specificity but may provide novel structures the further chemical modification of which may yield more promising drugs.


Assuntos
Anti-Inflamatórios , Macrófagos , Camundongos , Animais , Ligantes , Óxido Nítrico Sintase Tipo II/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Macrófagos/metabolismo , Células RAW 264.7 , Óxido Nítrico/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo
5.
JMIR Hum Factors ; 9(3): e37350, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35862171

RESUMO

BACKGROUND: HIV mobile health (mHealth) interventions often incorporate interactive peer-to-peer features. The user-generated content (UGC) created by these features can offer valuable design insights by revealing what topics and life events are most salient for participants, which can serve as targets for subsequent interventions. However, unstructured, textual UGC can be difficult to analyze. Interpretive thematic analyses can preserve rich narratives and latent themes but are labor-intensive and therefore scale poorly. Natural language processing (NLP) methods scale more readily but often produce only coarse descriptive results. Recent calls to advance the field have emphasized the untapped potential of combined NLP and qualitative analyses toward advancing user attunement in next-generation mHealth. OBJECTIVE: In this proof-of-concept analysis, we gain human-centered design insights by applying hybrid consecutive NLP-qualitative methods to UGC from an HIV mHealth forum. METHODS: UGC was extracted from Thrive With Me, a web app intervention for men living with HIV that includes an unstructured peer-to-peer support forum. In Python, topics were modeled by latent Dirichlet allocation. Rule-based sentiment analysis scored interactions by emotional valence. Using a novel ranking standard, the experientially richest and most emotionally polarized segments of UGC were condensed and then analyzed thematically in Dedoose. Design insights were then distilled from these themes. RESULTS: The refined topic model detected K=3 topics: A: disease coping; B: social adversities; C: salutations and check-ins. Strong intratopic themes included HIV medication adherence, survivorship, and relationship challenges. Negative UGC often involved strong negative reactions to external media events. Positive UGC often focused on gratitude for survival, well-being, and fellow users' support. CONCLUSIONS: With routinization, hybrid NLP-qualitative methods may be viable to rapidly characterize UGC in mHealth environments. Design principles point toward opportunities to align mHealth intervention features with the organically occurring uses captured in these analyses, for example, by foregrounding inspiring personal narratives and expressions of gratitude, or de-emphasizing anger-inducing media.

6.
Curr Protoc ; 1(11): e302, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794211

RESUMO

Drug-Target interaction predictions are an important cornerstone of computer-aided drug discovery. While predictive methods around individual targets have a long history, the application of proteome-scale models is relatively recent. In this overview, we will provide the context required to understand advances in this emerging field within computational drug discovery, evaluate emerging technologies for suitability to given tasks, and provide guidelines for the design and implementation of new drug-target interaction prediction models. We will discuss the validation approaches used, and propose a set of key criteria that should be applied to evaluate their validity. We note that we find widespread deficiencies in the existing literature, making it difficult to judge the practical effectiveness of some of the techniques proposed from their publications alone. We hope that this review may help remedy this situation and increase awareness of several sources of bias that may enter into commonly used cross-validation methods. © 2021 Cyclica Inc. Current Protocols published by Wiley Periodicals LLC.


Assuntos
Preparações Farmacêuticas , Proteoma , Desenvolvimento de Medicamentos , Descoberta de Drogas
7.
Arch Sex Behav ; 50(4): 1781-1792, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32728870

RESUMO

Despite being grouped together in epidemiological risk categories, gay, bisexual, and other men who have sex with men (GBM) are not a homogenous group. In addition to traditional segmentation along race, ethnicity, and socioeconomic status, many GBM also identify with sexual subcultural communities. Previous research has shown differences across a variety of health outcomes between these sexual subcultural communities. The purpose of this study was to determine whether HIV prevention practices among GBM differed according to sexual subcultural community. The study was conducted in collaboration with a popular social and sexual networking smartphone application company. A total of 23,577 GBM responded to the survey. A latent class analysis identified 6 distinct classes related to sexual subcultural community identification. We found significant differences across sociodemographic characteristics, HIV prevention practices, and condomless anal sex in the past 6 months related to sexual subculture identification. Findings suggest that sexual subcultural identity is related to decision-making around HIV prevention among GBM. Differences in HIV prevention strategies are likely a function of group norms, unique shared experiences among GBM identifying with a particular sexual subculture community, and sociodemographic characteristics associated with these groups. As such, sexual subculture identity should be considered in developing interventions and social marketing campaigns to increase uptake of biomedical HIV prevention tools among GBM. Identifying group norms and shared experiences related to HIV prevention practices among sexual subcultures is necessary to understand the role these identities play in lives of GBM, especially as it relates to their sexual health and well-being.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Comportamento Sexual , Minorias Sexuais e de Gênero , Bissexualidade , Preservativos , Infecções por HIV/prevenção & controle , Humanos , Masculino , Parceiros Sexuais , Smartphone
8.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20245944

RESUMO

BackgroundAzithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19. MethodsIn this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FindingsBetween 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1{middle dot}00; 95% confidence interval [CI] 0{middle dot}90-1{middle dot}12; p=0{middle dot}99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1{middle dot}03; 95% CI 0{middle dot}97-1{middle dot}10; p=0{middle dot}29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0{middle dot}97; 95% CI 0{middle dot}89-1{middle dot}07; p=0{middle dot}54). InterpretationIn patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication. FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).

9.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20083170

RESUMO

BackgroundThe COVID-19 pandemic has caused disruption across cancer pathways for diagnosis and treatment. In England, 32% of colorectal cancer (CRC) is diagnosed via urgent symptomatic referral from primary care, the "2-week-wait" (2WW) pathway. Access to routine endoscopy is likely to be a critical bottleneck causing delays in CRC management due to chronic limitation in capacity, acute competition for physician time, and safety concerns. MethodsWe used age-specific, stage-specific 10 year CRC survival for England 2007-2017 and 2WW CRC cases volumes. We used per-day hazard ratios of CRC survival generated from observational studies of CRC diagnosis-to-treatment interval to model the effect of different durations of per-patient delay. We utilised data from a large London observational study of faecal immunochemical testing (FIT) in symptomatic patients to model FIT-triage to mitigate delay to colonoscopy. FindingsModest delays result in significant reduction in survival from CRC with a 4-month delay resulting across age groups in [≥]20% reduction in survival in Stage 3 disease and in total over a year, 1,419 attributable deaths across the 11,266 CRC patients diagnosed via the 2WW pathway. FIT triage of >10 ug Hb/g would salvage 1,292/1,419 of the attributable deaths and reduce colonoscopy requirements by >80%. Diagnostic colonoscopy offers net survival in all age groups, providing nosocomial COVID-19 infection rates are kept low (<2{middle dot}5%). InterpretationTo avoid significant numbers of avoidable deaths from CRC, normal diagnostic and surgical throughput must be maintained. An accrued backlog of cases will present to primary care following release of lockdown, supranormal endoscopy capacity will be required to manage this without undue delays. FIT-triage of symptomatic cases provides a rational approach by which to avoid patient delay and mitigate pressure on capacity in endoscopy. This would also reduce exposure to nosocomial COVID-19 infection, relevant in particular to older patient groups. FundingBreast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR).

10.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20073833

RESUMO

BackgroundCancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival. MethodsWe generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations. FindingsPer year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of six months would cause attributable death of 10,555 of these individuals with loss of 205,024 life years. For cancer surgery, average life years gained (LYGs) per patient are 18{middle dot}1 under standard conditions and 15{middle dot}9 with a delay of six months (a loss of 2{middle dot}3 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2{middle dot}25 resource-adjusted life years gained (RALYGs) under standard conditions and 1{middle dot}98 RALYGs following delay of six months. For 94,912 hospital COVID-19 admissions, there are 474,505 LYGs requiring of 1,097,937 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5{middle dot}0 LYG and 0{middle dot}43 RALYGs. InterpretationDelay of six months in surgery for incident cancers would mitigate 43% of life years gained by hospitalisation of an equivalent volume of admissions for community acquired COVID-19. This rises to 62% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued. FundingBreast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR)

11.
J Acquir Immune Defic Syndr ; 83(3): 215-222, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809309

RESUMO

BACKGROUND: Several studies have demonstrated no linked HIV transmissions in serodifferent sexual encounters where the partner with HIV has an undetectable viral load. As a result, awareness and dissemination of treatment as prevention, and movements such as "Undetectable = Untransmittable" (U = U), has grown. SETTING: We conducted an online cross-sectional survey from November 2017 through September 2018 to gather data from a total of 111,747 sexual minority men (SMM) in the United States. METHODS: Participants provided sociodemographic data and answered questions regarding biomedical status, HIV and STI prevention behaviors, drug use, condomless anal sex, and perceived accuracy of the U = U message. We conducted analyses to understand factors associated with perceived accuracy of U = U stratified by HIV status. RESULTS: Overall, 53.2% of the sample perceived U = U as accurate, with the highest rates among HIV-positive SMM (83.9%), followed by HIV-negative (53.8%) and status-unknown (39.0%) SMM. Multivariable models showed accuracy beliefs were, on average, 1-2% higher for each consecutive month of recruitment. Consistent with previous work, there was greater heterogeneity among HIV-negative and unknown men, with several factors differentiating perceived accuracy, compared with SMM with HIV. Perceived transmission risk levels with undetectable partners were skewed well above accurate levels, and greater perceived transmission risk was associated with lower perceived accuracy of U = U. CONCLUSIONS: Public confidence in treatment as prevention and U = U is growing, but clear, unequivocal messaging about the effectiveness of U = U is critical. Owing to misunderstandings of risk, language that focuses on protective benefits rather than transmission risks may reach more people and allow for better comparisons with PrEP and condoms.


Assuntos
Infecções por HIV/transmissão , Infecções por HIV/virologia , Minorias Sexuais e de Gênero , Carga Viral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Parceiros Sexuais , Estados Unidos/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Adulto Jovem
12.
S D Med ; 71(7): 294-298, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30005538

RESUMO

Adenoid cystic carcinoma (ACC) is a rare malignant secretory gland tumor. It is characterized by slow growth, long clinical course, local recurrences, and distant metastases. In the sinonasal tract, it most commonly arises in the maxillary sinus. It often presents at an advanced stage with perineural spread (PNS). Our patient presented with left-sided facial numbness without other symptoms. The numbness was localized to the left cheek, left side of nose, and left upper lip. Magnetic resonance imaging (MRI) of the brain revealed an enhancing lesion involving the left maxillary sinus with orbital invasion and posterior extension into the cavernous sinus. Transnasal endoscopic exploration with tissue removal revealed ACC. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed no evidence of distant metastases. Presentation of sinonasal ACC (SNACC) is variable depending on the involved structures. Characteristic PNS with ACC may cause neuropathic symptoms. This case displays a unique presentation of an advanced ACC of the maxillary sinus manifesting as isolated unilateral trigeminal anesthesia without sinonasal symptoms. The patient also failed to demonstrate any ocular or oculomotor symptoms despite extensive involvement of the orbit and surrounding structures. This case highlights the importance of recognizing ACC due to its association with late symptomatic manifestations. It also reinforces the need for clinical diligence with the workup of new onset neuropathic symptoms in the maxillary distribution of the trigeminal nerve.


Assuntos
Carcinoma Adenoide Cístico/complicações , Hipestesia/etiologia , Neoplasias do Seio Maxilar/complicações , Seio Maxilar , Doenças do Nervo Trigêmeo/etiologia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/patologia , Seio Cavernoso/diagnóstico por imagem , Seio Cavernoso/patologia , Humanos , Imageamento por Ressonância Magnética , Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/patologia , Órbita/diagnóstico por imagem
15.
Practitioner ; 257(1761): 19-21, 3, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23808127

RESUMO

The age at which individuals are most physically aggressive is 22 months. However, some children fail to inhibit this normal aggression and by the time they are three or four are showing signs of oppositional defiant disorder. In older children persistent antisocial behaviour is classified as conduct disorder. At any age, antisocial behaviour is on a continuum, and while the most severe 5% or so will meet diagnostic criteria, those falling short are often described as having conduct problems. Epidemiological follow-up surveys show that the risk of poor outcomes in antisocial children is very high. The causes are multiple but two sets of factors stand out. First, genetic predisposition. Even children adopted away from violent or criminal parents have three or four times the rate of antisocial behaviour and second, poor parenting. Watching and waiting is a reasonable strategy if the antisocial behaviour is not very severe. It is important to be vigilant for severe tantrums or aggression occurring almost every day, harsh, rough, or inconsistent parenting and coexistent ADHD. If severity is moderate, referral to an evidence-based parenting group would be a good first move. If this fails to make things better, or if the child or parent has a comorbid condition, referral to CAMHS is indicated. For older children, aged 10 to 17, there are effective interventions such as anger management CBT and parenting groups for adolescents.


Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo , Pais , Adolescente , Adulto , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/genética , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/terapia , Criança , Pré-Escolar , Transtorno da Conduta/diagnóstico , Transtorno da Conduta/etiologia , Transtorno da Conduta/genética , Transtorno da Conduta/terapia , Terapia Familiar/métodos , Humanos , Lactente , Pais/educação , Pais/psicologia
16.
Health Econ ; 20(10): 1241-56, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20882577

RESUMO

Studies show a relationship between oral inflammatory processes and cardiovascular risk factors, suggesting that dental care may reduce the risk of cardiovascular disease (CVD) events. However, due to the differences between men and women in the development and presentation of CVD, such effects may vary by sex. We use a valid set of instrumental variables to evaluate these issues and include a test of essential heterogeneity. CVD events include new occurrences of heart attack (including death from heart attack), stroke (including death from stroke), angina, and congestive heart failure. Controls include age, race, education, marital status, foreign birthplace, and cardiovascular risk factors (health status, body mass index, alcohol use, smoking status, diabetes status, high-blood-pressure status, physical activity, and depression). Our analysis finds no evidence of essential heterogeneity. We find the minimum average treatment effect for women to be -0.01, but find no treatment effect for men. This suggests that women who receive dental care may reduce their risk of future CVD events by at least one-third. The findings may only apply to married middle-aged and older individuals as the data set is only representative for this group.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Assistência Odontológica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Fatores de Risco , Comportamento de Redução do Risco , Estados Unidos/epidemiologia
17.
Opt Express ; 18(7): 7131-7, 2010 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-20389734

RESUMO

Using a four-mode theoretical analysis we show that highly efficient anti-Stokes conversion in waveguides is more challenging to realize in practice than previously thought. By including the dynamics of conversion to 2(nd) Stokes via stimulated Raman scattering and four-wave mixing, models predict only narrow, unstable regions of highly efficient anti-Stokes conversion. Experimental results of single-pass Raman conversion in confined capillary waveguides validate these predictions. This places more stringent conditions on systems that require highly efficient single-pass anti-Stokes conversion.

18.
Am J Cardiol ; 105(3): 378-82, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20102952

RESUMO

More patients who are receiving therapy with a left ventricular assist device (LVAD) also have an implantable cardioverter-defibrillator (ICD). The aim of the present study was to describe the outcomes and device interactions of simultaneous therapy with an ICD and a LVAD. We evaluated 76 patients with class IV heart failure (age 52 + or - 12 years, left ventricular ejection fraction 0.13 + or - 0.05%, 88% men, 61% nonischemic cardiomyopathy) with both an ICD and a LVAD. The median follow-up with both devices was 156 days. A LVAD with a pulsatile and continuous flow pump was used in 53 (70%) and 23 (30%) patients, respectively. Of the 76 patients, 12 (16%) received a total of 54 ICD therapies. Of the ICD therapies, 88% were appropriate. Of the 76 patients, 55 (72%) underwent heart transplantation a median of 146 days after LVAD implantation. Twelve patients (16%) died during simultaneous ICD and LVAD therapy. Interactions between the LVAD and ICD occurred in 2 patients (2.7%) with continuous flow pumps (HeartMate II). In both cases, telemetry failure occurred after LVAD implantation with 2 different models of ICDs from the same manufacturer. No ICD therapies occurred because of device-related interactions. In conclusion, simultaneous ICD and LVAD therapy in patients with severe congestive heart failure is safe and clinically feasible. Interactions between the devices are uncommon and appear limited to specific models of ICDs.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca/terapia , Coração Auxiliar , Adulto , Desfibriladores Implantáveis/efeitos adversos , Desenho de Equipamento , Falha de Equipamento , Análise de Falha de Equipamento , Estudos de Viabilidade , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Auxiliar/efeitos adversos , Humanos , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
19.
J Infect ; 53(1): e43-6, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16253335

RESUMO

A patient with abdominal sepsis, had both intra and extracellular bacteria in a blood smear, and high levels of neutrophil membrane CD64 and HLA-Dr. Intracellular bacteria are only observed in the terminal phase of a sepsis. Our patient recovered, suggesting that a high expression of neutrophil CD64 is indicative for a good prognosis.


Assuntos
Antígenos HLA-DR/metabolismo , Neutrófilos/imunologia , Receptores de IgG/metabolismo , Sepse/etiologia , Sepse/imunologia , Abdome , Bacteriemia/microbiologia , Pré-Escolar , Enterobacter aerogenes/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Enterococcus faecalis/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Neutrófilos/microbiologia
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