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INTRODUCTION: Expanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. METHODS: An electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). RESULTS: Overall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. CONCLUSIONS: Our review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.
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Transplante de Coração , Hepatite B , Humanos , Masculino , Feminino , Hepatite B/epidemiologia , Hepatite B/tratamento farmacológico , Vírus da Hepatite B , Transplante de Coração/efeitos adversos , Antivirais/uso terapêutico , Anticorpos Anti-Hepatite B/uso terapêutico , Doadores de Tecidos , Antígenos do Núcleo do Vírus da Hepatite B/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Improvement in continuous-flow left ventricular assist device (CF-LVAD) technology has translated to better outcomes for patients on CF-LVAD support as a bridge-to-transplant. However, data are lacking regarding the subset of CF-LVAD patients with renal failure awaiting simultaneous heart-kidney transplant (HKTx). We sought to better understand the characteristics and outcomes of patients in this group. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify adult patients listed for heart transplant (HTx) or HKTx from January 1, 2009 to March 31, 2017. Patients were followed from time on waitlist to either removal from waitlist or transplantation. Demographic and clinical data for HTx and HKTx patients were assessed. Kaplan-Meier analysis assessed waitlist and post-transplant survival. For waitlisted patients, both death and removal from the waitlist due to deteriorating medical condition were considered events. RESULTS: Overall, 26 638 patients registered for transplant were analyzed. 25 111 (94%) were listed for HTx, and 1527 (6%) for HKTx. 7683 (29%) patients listed for HTx had CF-LVAD support. For those listed for HKTx, 441 (28%) underwent dialysis alone, 256 (17%) had CF-LVAD support alone, and 85 (6%) were treated with both CF-LVAD and dialysis. 15 567 (58%) underwent HTx, and 621 (2%) underwent HKTx. In these groups, post-transplant survival was similar (p = 0.06). Patients listed for HKTx treated with both dialysis and CF-LVAD had significantly worse waitlist survival compared to HKTx recipients (p < 0.001). CONCLUSION: Post-transplant survival is comparable between HTx and HKTx, and early survival is similar between HTx patients and those listed for HTx with CF-LVAD support. However, outcomes on the waitlist for HKTx in CF-LVAD patients on dialysis is significantly worse compared to HKTx recipients. This highlights the need to better account for this patient population when allocating organs.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Transplante de Rim , Adulto , Humanos , Transplante de Rim/efeitos adversos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Resultado do Tratamento , Transplante de Coração/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Health policy makers and advocates increasingly utilize online resources for policy-relevant knowledge. Knowledge brokering is one potential mechanism to encourage the use of research evidence in policy making, but the mechanisms of knowledge brokerage in online spaces are understudied. This work looks at knowledge brokerage through the launch of Project ASPEN, an online knowledge portal developed in response to a New Jersey legislative act that established a pilot program for adolescent depression screening for young adults in grades 7-12. OBJECTIVE: This study compares the ability to drive policy brief downloads by policy makers and advocates from the Project ASPEN knowledge portal using a variety of online methods to promote the knowledge portal. METHODS: The knowledge portal was launched on February 1, 2022, and a Google Ad campaign was run between February 27, 2022, and March 26, 2022. Subsequently, a targeted social media campaign, an email campaign, and tailored research presentations were used to promote the website. Promotional activities ended on May 31, 2022. Website analytics were used to track a variety of actions including new users coming to the website, page views, and policy brief downloads. Statistical analysis was used to assess the efficacy of different approaches. RESULTS: The campaign generated 2837 unique user visits to the knowledge portal and 4713 page views. In addition, the campaign generated 6.5 policy web page views/day and 0.7 policy brief downloads/day compared with 1.8 views/day and 0.5 downloads/day in the month following the campaign. The rate of policy brief page view conversions was significantly higher for Google Ads compared with other channels such as email (16.0 vs 5.4; P<.001) and tailored research presentations (16.0 vs 0.8; P<.001). The download conversion rate for Google Ads was significantly higher compared with social media (1.2 vs 0.1; P<.001) and knowledge brokering activities (1.2 vs 0.2; P<.001). By contrast, the download conversion rate for the email campaign was significantly higher than that for social media (1.0 vs 0.1; P<.001) and tailored research presentations (1.0 vs 0.2; P<.001). While Google Ads for this campaign cost an average of US $2.09 per click, the cost per conversion was US $11 per conversion to drive targeted policy web page views and US $147 per conversion to drive policy brief downloads. While other approaches drove less traffic, those approaches were more targeted and cost-effective. CONCLUSIONS: Four tactics were tested to drive user engagement with policy briefs on the Project ASPEN knowledge portal. Google Ads was shown to be effective in driving a high volume of policy web page views but was ineffective in terms of relative costs. More targeted approaches such as email campaigns and tailored research presentations given to policy makers and advocates to promote the use of research evidence on the knowledge portal website are likely to be more effective when balancing goals and cost-effectiveness.
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Política de Saúde , Mídias Sociais , Adolescente , Adulto Jovem , Humanos , Projetos de Pesquisa , Formulação de PolíticasRESUMO
The future of work will be measured. The increasing and widespread adoption of analytics, the use of digital inputs and outputs to inform organizational decision making, makes the communication of data central to organizing. This article applies and extends signaling theory to provide a framework for the study of analytics as communication. We report three cases that offer examples of dubious, selective, and ambiguous signaling in the activities of workers seeking to shape the meaning of data within the practice of analytics. The analysis casts the future of work as a game of strategic moves between organizations, seeking to measure behaviors and quantify the performance of work, and workers, altering their behavioral signaling to meet situated goals. The framework developed offers a guide for future examinations of the asymmetric relationship between management and workers as organizations adopt metrics to monitor and evaluate work.
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Percutaneous biventricular assist devices (BiVAD) are a recently developed treatment option for severe cardiogenic shock. This systematic review sought to identify indications and outcomes of patients placed on percutaneous BiVAD support. An electronic search was performed to identify all appropriate studies utilizing a percutaneous BiVAD configuration. Fifteen studies comprising of 20 patients were identified. Individual patient survival and outcomes data were combined for statistical analysis. All 20 patients were supported with a microaxial LVAD, 12/20 (60%) of those patients were supported with a microaxial (RMA) right ventricular assist device (RVAD), and the remaining 8/20 (40%) patients were supported with a centrifugal extracorporeal RVAD (RCF). All patients presented with cardiogenic shock, and of these, 12/20 (60%) presented with a non-ischemic etiology vs 8/20 (40%) with ischemic disease. For the RMA group, RVAD support was significantly longer [RMA 5 (IQR 4-7) days vs RCF 1 (IQR 1-2) days, p = 0.03]. Intravascular hemolysis post-BiVAD occurred in three patients (27.3%) [RMA 3 (33.3%) vs RCF 0 (0%), p = 0.94]. Five patients received a durable left ventricular assist device, one patient received a total artificial heart, and one patient underwent a heart transplantation. Estimated 30-day mortality was 15.0%, and 78.6% were discharged alive. Both strategies for percutaneous BiVAD support appear to be viable options for severe cardiogenic shock.
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Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Estudos Retrospectivos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Resultado do TratamentoRESUMO
STUDY: There is no widely accepted donor to recipient size-match metric to predict outcomes in cardiac transplant. The predictive ability of size-match metrics has not been studied when recipients are stratified by heart failure etiology. We sought to assess the performance of commonly used size metrics to predict survival after heart transplant, accounting for restrictive versus non-restrictive pathology. METHODS: The UNOS registry was queried from 2000 to 2017 for all primary isolated heart transplants. Donor-recipient ratios were calculated for commonly used size metrics and their association with survival was assessed using continuous, nonlinear analysis. RESULTS: 29 817 patients were identified. Height (P < .001), predicted heart mass (PHM) (P = .003), ideal body weight (IBW) (P < .001) and body mass index (BMI) (P = .003) ratios were significantly associated with survival, while weight and body surface area (BSA) ratios were not. When stratified, only BMI ratio retained significance for both restrictive (P = .051) and non-restrictive (P = .003) subsets. Recipients with restrictive etiology had increased risk of mortality with both a lower and higher BMI ratio. CONCLUSIONS: While many metrics show association with survival in the non-restrictive subset, BMI is the only metric that retains significance in the restrictive subset. Recipients with restrictive and non-restrictive etiologies of heart failure tolerate size mismatch differently.
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Insuficiência Cardíaca , Transplante de Coração , Obtenção de Tecidos e Órgãos , Benchmarking , Sobrevivência de Enxerto , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Humanos , Tamanho do Órgão , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: Hemocompatibility-related adverse events (HRAE) negatively influence survival. However, no study has examined the impact of these events on health-related quality of life (HRQOL) and functional outcomes following continuous-flow left ventricular assist device implantation (CF-LVAD). We assessed the impact of HRAE events on HRQOL and hypothesized that HRAE's adversely impact HRQOL and functional outcomes. METHODS: INTERMACS database identified patients undergoing primary CF-LVAD implantation from 2008 to 2017. HRAEs included stroke, non-surgical bleeding, hemolysis, and pump thrombosis and were identified as defined in the literature. HRAEs were further stratified as Tier 1-2 and disabling stroke events. Time-series analysis was executed for HRAE patients with values pre-HRAE, post-HRAE, and closest to 12 months follow up. Local polynomial regression curves modeling individual patients were superimposed into "spaghetti" plots. RESULTS: All HRQOL and functional metrics improved in patients over time, despite HRAE complications. However, these patient metrics were significantly reduced compared to the non-HRAE cohort. Advanced data visualization techniques noted a decline after experiencing an HRAE with a subsequent recovery to baseline levels or higher. Six-minute walk test (6MWT) was noted to be most affected in the post-HRAE period but recovered similar to other metrics. CONCLUSIONS: The burden of HRAE following CF-LVAD implantation did not negatively impact the quality of life. However, the 6MWT did not increase in the post-HRAE period in all HRAE patients. Improvement of heart failure symptoms after CF-LVAD coupled with optimal management following the HRAE act to preserve the enhanced quality of life.
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Insuficiência Cardíaca , Coração Auxiliar , Acidente Vascular Cerebral , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Hemólise , Humanos , Qualidade de Vida , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium spiny neurons (MSNs) via dorsal striatal microelectrode arrays in mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to "switch" response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time-related ramping activity and response-related activity increased with task experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time-related ramping activity. Finally, we found that a subset of MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.
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Corpo Estriado , Percepção do Tempo , Animais , Camundongos , Neurônios , RecompensaRESUMO
Prothrombin complex concentrate (PCC) administration has increased among cardiac surgery patients in recent years; however, use in LVAD implantation/exchange is not widespread due to the fear of thrombotic complications. The purpose of this study was to compare the clinical outcomes of patients undergoing LVAD implantation/exchange with intraoperative PCC administration versus traditional transfusion practices alone. Adult LVAD implants/exchanges at our institution between 2015 and 2018 were included. Patients were categorized as receiving intraoperative PCC or no-PCC (traditional). The primary outcome was the need for allogenic transfusion and transfusion volume at 48 hours after initial intensive care unit (ICU) admission. Secondary outcomes included metrics of morbidity and mortality. A total of 160 patients (39 PCC, 121 traditional) were analyzed. In unadjusted analysis, patients in the PCC group received lower intraoperative transfusion volumes compared to the traditional group although not statistically significant (1464 mL [IQR 796, 4876] vs. 2568 mL [IQR 1292, 3606]; P value .37). In the fully adjusted analysis, patients in the PCC group had increased odds of transfusion within 48 hours of ICU admission (OR 4.06, 95% CI: 1.35-12.20; P < .01); however, there was no significant difference in transfusion volumes (P = .09). Patients receiving PCCs had higher incidence of deep vein thrombosis (10.3% vs. 0%; P < .01) and 30-day mortality (17.9% vs. 4.1%; P < .01). LVAD pump thrombosis occurred in 2.6% versus 0.8% in the PCC and traditional groups, respectively; P = .98. Patients undergoing LVAD implantation and exchange represent a complex surgical cohort. The results of this study suggest that the intraoperative PCC use during LVAD implant/exchange was associated with reduced intraoperative transfusions. Intraoperative PCC use was, however, associated with higher odds of postoperative transfusion, although transfusion volumes were not significantly different. While the deep vein thrombosis and 30-day mortality rates were higher in the PCC group, these results are likely related to the degree of surgical and patient complexity rather than PCC use itself. Further studies are needed to assess PCC use in this surgical cohort.
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Fatores de Coagulação Sanguínea/administração & dosagem , Coração Auxiliar , Implantação de Prótese/métodos , Idoso , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Ventricular arrhythmias (VA) are not uncommon after continuous-flow left ventricular assist device (CF-LVAD) implantation. In this systematic review, we sought to identify the patterns of VA that occurred following CF-LVAD implantation and evaluate their outcomes. An electronic search was performed to identify all articles reporting the development of VA following CF-LVAD implantation. VA was defined as any episode of ventricular fibrillation (VF) or sustained (>30 seconds) ventricular tachycardia (VT). Eleven studies were pooled for the analysis that included 393 CF-LVAD patients with VA. The mean patient age was 57 years [95%CI: 54; 61] and 82% [95%CI: 73; 88] were male. Overall, 37% [95%CI: 19; 60] of patients experienced a new onset VA after CF-LVAD implantation, while 60% [95%CI: 51; 69] of patients had a prior history of VA. Overall, 88% of patients [95%CI: 78; 94] were supported on HeartMate II CF-LVAD, 6% [95%CI: 3; 14] on HeartWare HVAD, and 6% [95%CI: 2; 13] on other CF-LVADs. VA was symptomatic in 47% [95%CI: 28; 68] of patients and in 50% [95%CI: 37; 52], early VA (<30 days from CF-LVAD) was observed. The 30-day mortality rate was 7% [95%CI: 5; 11]. Mean follow-up was 22.9 months [95%CI: 4.8; 40.8], during which 27% [95%CI: 17; 39] of patients underwent heart transplantation. In conclusion, approximately a third of patients had new VA following CF-LVAD placement. VA in CF-LVAD patients is often symptomatic, necessitates treatment, and carries a worse prognosis.
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Arritmias Cardíacas/etiologia , Coração Auxiliar/efeitos adversos , Humanos , Fatores de Risco , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/etiologiaRESUMO
Gastrointestinal bleeding (GIB) is a common adverse event after continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate patterns of GIB development and related outcomes in CF-LVAD recipients. An electronic search was performed to identify all articles related to GIB in the setting of CF-LVAD implantation. A total of 34 studies involving 1087 patients were pooled for analysis. Mean patient age was 60 years (95% CI 57-64) and 24% (95% CI 21-28%) were female. The mean time from CF-LVAD implantation to the first GIB was 54 days (95% CI 24-84) with 40% (95% CI 34-45%) of patients having multiple episodes of GIB. Anemia was present in 75% (95% CI 41-93%) and the most common etiology of bleeding was arteriovenous malformations (36% [95% CI 24-50%]). The mean duration of follow-up was 14.6 months (95% CI 6.9-22.3) during which the all-cause mortality rate was 21% (95% CI 12-36%) and the mortality rate from GIB was 4% (95% CI 2-9%). Thromboembolic events occurred in 32% (95% CI 22-44%) of patients with an ischemic stroke rate of 16% (95% CI 3-51%) and a pump thrombosis rate of 8% (95%CI 3-22%). Heart transplantation was performed in 31% (95% CI 18-47%) of patients, after which 0% (95% CI 0-10%) experienced recurrent GIB. GIB is a major source of morbidity among CF-LVAD recipients. While death due to GIB is rare, cessation of anticoagulation during treatment increases the risk of subsequent thrombotic events. Heart transplant in these patients appears to reliably resolve the risk of future GIB.
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Hemorragia Gastrointestinal/etiologia , Coração Auxiliar/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Análise de SobrevidaRESUMO
BACKGROUND AND AIM OF THE STUDY: Ventricular septal defect (VSD) following myocardial infarction (MI) is a relatively infrequent complication with high mortality. We sought to investigate the effect of concomitant coronary artery bypass graft (CABG) on outcomes following post-MI VSD repair. METHODS: Electronic search was performed to identify all relevant studies published from 2000 to 2018. Sixty-seven studies were selected for the analysis comprising 2174 patients with post-MI VSD. Demographic information, perioperative variables, and outcomes including survival data were extracted and pooled for systematic review and meta-analysis. RESULTS: Single-vessel disease was most common (47%, 95% confidence interval [CI], 42-52), left anterior descending coronary artery was the most commonly involved vessel (55%, 95% CI, 46-63), and anterior wall was the most commonly affected territory (57%, 95% CI, 51-63). Concomitant CABG was performed in 52% (95% CI, 46-57) of patients. Of these, infarcted territory was re-vascularized in 54% (95% CI, 23-82). A residual/recurrent shunt was present in 29% (95% CI, 24-34) of patients. Of these, surgical repair was performed in 35% (95% CI, 28-41) and transcatheter repair in 11% (95% CI, 6-21). Thirty-day mortality was 30% (95% CI, 26-35) in patients who had preoperative coronary angiogram, and 58% (95% CI, 43-71) in those who did not (P < .01). No significant survival difference observed between those who had concomitant CABG vs those without CABG. CONCLUSIONS: Concomitant CABG did not have a significant effect on survival following VSD repair. Revascularization should be weighed against the risks associated with prolonged cardiopulmonary bypass.
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Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte de Artéria Coronária , Comunicação Interventricular/cirurgia , Ponte Cardiopulmonar/efeitos adversos , Feminino , Comunicação Interventricular/etiologia , Comunicação Interventricular/mortalidade , Humanos , Masculino , Infarto do Miocárdio/complicações , Taxa de Sobrevida , Resultado do TratamentoRESUMO
No standardized treatment algorithm exists for the management of continuous-flow left ventricular assist device (CF-LVAD)-specific infections. The aim of this systematic review and meta-analysis was to compare the outcomes of CF-LVAD-specific infections as managed by device exchange to other treatment modalities not involving device exchange. Electronic search was performed to identify all studies in the English literature relating to the management of CF-LVAD-specific infections. All identified articles were systematically assessed for selection criteria. Thirteen studies with 158 cases of CF-LVAD-specific infection were pooled for analysis. Overall, 18/158 (11.4%) patients underwent CF-LVAD exchange, and 140/158 (88.6%) patients were treated with non-exchange modalities. The proportion of patients with isolated driveline infections or pump or pocket infections did not differ significantly between the groups. During a mean follow-up of 290 days, there were no significant differences in the overall mortality [exchange 17.6% (4.3-50.6) vs. non-exchange 23.3% (15.8-32.9), P = 0.67] and infection recurrence rates [exchange 26.7% (8.7-58.0) vs. non-exchange 38.6% (15.4-68.5), P = 0.56]. In the setting of CF-LVAD-specific infections, device exchange does not appear to confer an advantage in the overall mortality and infection recurrence as compared to non-exchange modalities.
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Remoção de Dispositivo , Coração Auxiliar/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/terapia , Ventrículos do Coração/fisiopatologia , Humanos , Infecções Relacionadas à Prótese/fisiopatologia , Recidiva , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: 15% of cerebral venous thrombosis (CVT) patients have poor outcomes despite anticoagulation. Uncontrolled studies suggest that endovascular approaches may benefit such patients. In this study, we analyze Nationwide Inpatient Sample (NIS) data to evaluate the safety and efficacy of endovascular therapy (ET) versus medical management in CVT. We also examined the yearly trends of ET utilization in the United States. METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification codes were utilized to identify CVT patients who received ET. To make the data nationally representative, weights were applied per NIS recommendations. Since ET was not randomly assigned to patients and was likely to be influenced by disease severity, propensity score weighting methods were utilized to correct for this treatment selection bias. Outcome variables included in-hospital mortality and discharge disposition. To determine if our primary outcomes were associated with ET, we used weighted multivariable logistic regression analyses. RESULTS: Of the 49,952 estimated CVT cases, 48,704 (97%) received medical management and 1248 (3%) received ET (mechanical thrombectomy [MT] alone, Nâ¯=â¯269 [21%], MT ± thrombolysis, Nâ¯=â¯297 [24%], and thrombolysis alone, Nâ¯=â¯682 [55%]). Patients who received ET were older with more CVT associated complications including venous infarct, intracranial hemorrhage, coma, seizure, and cerebral edema. There was a significant yearly rise in the use of ET, with a trend favoring MT versus thrombolysis alone. ET was independently associated with an increased risk of death (odds ratio 1.96, 95% confidence interval 1.15-3.32). CONCLUSIONS: Patients receiving ET experienced higher mortality after adjusting for age and CVT associated complications. Large, well designed prospective randomized trials are warranted for further evaluation of the safety and efficacy of ETs.
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Procedimentos Endovasculares/tendências , Pacientes Internados , Trombose Intracraniana/terapia , Padrões de Prática Médica/tendências , Trombectomia/tendências , Terapia Trombolítica/tendências , Trombose Venosa/terapia , Adulto , Idoso , Fármacos Cardiovasculares/uso terapêutico , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/mortalidade , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/mortalidadeRESUMO
Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction. Control and previously defeated rats did not differ in either DOPA accumulation following amino acid decarboxylase inhibition (NSD-1015 100 mg/kg ip.) or total/phosphorylated tyrosine hydroxylase protein expression, suggesting dopamine synthesis in the adult mPFC is not altered by adolescent defeat. However, exposure to adolescent defeat caused greater decreases in extracellular dopamine release (measured using in vivo chronoamperometry) in the adult mPFC upon local infusion of the D2 receptor agonist quinpirole (3 nM), implying greater D2 autoreceptor function. Equally enhanced D2 autoreceptor-mediated inhibition of dopamine release is seen in the adolescent (P40 or P49) mPFC, which declines in control rats by adulthood. However, this developmental decrease in autoreceptor function is absent following adolescent defeat, suggesting retention of an adolescent-like phenotype into adulthood. Current and previous findings indicate adolescent defeat decreases extracellular dopamine availability in the adult mPFC via both enhanced inhibition of dopamine release and increased dopamine clearance, which may be viable targets for improving treatment of cognitive deficits seen in neuropsychiatric disorders promoted by adolescent stress.
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Autorreceptores/metabolismo , Dominação-Subordinação , Dopamina/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D2/metabolismo , Estresse Psicológico/metabolismo , Fatores Etários , Animais , Comportamento Animal/fisiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Although ecosystem services research has become common, few efforts are directed toward in-depth understanding of the specific ecological quantities people value. The theoretical framework of final ecosystem services focuses attention on such measurable attributes, as a common currency for social-ecological systems research. Environmental communications as well as ecological monitoring and analysis efforts could be enhanced through increased documentation of final ecosystem services. For example, small changes in the way ecosystems are described could strongly influence relevance to the public and improve the foundation for environmental decision making. Focusing on rivers and streams, we conducted a content analysis of existing publications to document the breadth and frequency with which various measurable attributes, such as flooding, water quality characteristics, and wildlife appeared in different news sources over a multiyear timeline. In addition to attributes, motivations for human interest in river-related resources were also coded, such as recreation or preservation for future generations. To allow testing of differences between materials written for different audiences, three sources were sampled: a blog hosted by National Geographic, New York Times articles, and Wall Street Journal articles. The coding approach was rigorously tested in a pilot phase, with measures developed to ensure high data quality, including use of two independent coders. Results show numerous similarities across sources with some notable differences in emphasis. Significant relationships between groups of attribute and motivation codes were also found, one outcome of which is further support for the importance of nonuse values for fish and wildlife. Besides offering insight on ecosystem services, the project demonstrates an in-depth quantitative approach to analyzing preexisting qualitative data.
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Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders; however, its mechanism is not completely understood. Compared with other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling. This communication mode during which burst firing of DA neurons generates rapid changes in extracellular DA, the so-called DA transients, is critically implicated in reward learning. Here, we investigate MOD effects on phasic DA signaling in the striatum of urethane-anesthetized rats with fast-scan cyclic voltammetry. We found that MOD (30-300 mg/kg i.p.) robustly increases the amplitude of electrically evoked phasic-like DA signals in a time- and dose-dependent fashion, with greater effects in dorsal versus ventral striata. MOD-induced enhancement of these electrically evoked amplitudes was mediated preferentially by increased DA release compared with decreased DA uptake. Principal component regression of nonelectrically evoked recordings revealed negligible changes in basal DA with high-dose MOD (300 mg/kg i.p.). Finally, in the presence of the D2 DA antagonist, raclopride, low-dose MOD (30 mg/kg i.p.) robustly elicited DA transients in dorsal and ventral striata. Taken together, these results suggest that activation of phasic DA signaling is an important mechanism underlying the clinical efficacy of MOD.
Assuntos
Compostos Benzidrílicos/farmacologia , Dopamina/metabolismo , Neostriado/citologia , Neostriado/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Estimulação Elétrica , Masculino , Modafinila , Neostriado/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes.
Assuntos
Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Vias Neurais/fisiologia , Testes Neuropsicológicos , Oxigênio/sangue , Descanso , Recompensa , Adulto JovemRESUMO
The idea that similarity might be an engine of inductive inference dates back at least as far as David Hume. However, Hume's thesis is difficult to test without begging the question, since judgments of similarity may be infected by inferential processes. We present a one-parameter model of category-based induction that generates predictions about arbitrary statements of conditional probability over a predicate and a set of items. The prediction is based on the unconditional probabilities and similarities that characterize that predicate and those items. To test Hume's thesis, we collected brain activation from various regions of the ventral visual stream during a categorization task that did not invite comparison of categories. We then calculated the similarity of those activation patterns using a simple measure of vectorwise similarity and supplied those similarities to the model. The model's outputs correlated well with subjects' judgments of conditional probability. Our results represent a promising first step toward confirming Hume's thesis; similarity, assessed without reference to induction, may well drive inductive inference.
Assuntos
Encéfalo/fisiologia , Modelos Psicológicos , Pensamento/fisiologia , Adolescente , Adulto , Feminino , Humanos , Julgamento/fisiologia , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Testes Neuropsicológicos , Probabilidade , Processamento de Sinais Assistido por Computador , Vias Visuais/fisiologia , Adulto JovemRESUMO
Time is a ubiquitous dimension of behaviour. A new study demonstrates that low-dimensional temporal drift in rodent anterior cingulate ensembles encodes cumulative experience. These data provide fresh insight into how neurons encode extended periods of time to guide high-level behaviours.