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1.
Dev Psychol ; 60(4): 649-664, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38483484

RESUMO

Adolescence is a critical developmental period that is marked by drastic changes in face recognition, which are reflected in patterns of bias (i.e., superior recognition for some individuals compared to others). Here, we evaluate how race is perceived during face recognition and whether adolescents exhibit an own-race bias (ORB). We conducted a Bayesian meta-analysis to estimate the summary effect size of the ORB across 16 unique studies (38 effect sizes) with 1,321 adolescent participants between the ages of ∼10-22 years of age. This meta-analytic approach allowed us to inform the analysis with prior findings from the adult literature and evaluate how well they fit the adolescent literature. We report a positive, small ORB (Hedges's g = 0.24) that was evident under increasing levels of uncertainty in the analysis. The magnitude of the ORB was not systematically impacted by participant age or race, which is inconsistent with predictions from perceptual expertise and social cognitive theories. Critically, our findings are limited in generalizability by the study samples, which largely include White adolescents in White-dominant countries. Future longitudinal studies that include racially diverse samples and measure social context, perceiver motivation, peer reorientation, social network composition, and ethnic-racial identity development are critical for understanding the presence, magnitude, and relative flexibility of the ORB in adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Reconhecimento Facial , Grupos Raciais , Adolescente , Criança , Humanos , Adulto Jovem , Teorema de Bayes , Grupo Associado , Reconhecimento Psicológico
2.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473752

RESUMO

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.


Assuntos
Glioma , Humanos , Linhagem Celular Tumoral , Compostos Benzidrílicos/farmacologia , Fenóis/farmacologia
3.
Nat Commun ; 15(1): 1533, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378868

RESUMO

CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7-47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5-64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pretreatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and preexisting anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.


Assuntos
Anilidas , Anticorpos Monoclonais , Neoplasias Colorretais , Piridinas , Humanos , Anticorpos Monoclonais/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
Soc Cogn Affect Neurosci ; 18(1)2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978845

RESUMO

In the current study, we combined sociometric nominations and neuroimaging techniques to examine adolescents' neural tracking of peers from their real-world social network that varied in social preferences and popularity. Adolescent participants from an entire school district (N = 873) completed peer sociometric nominations of their grade at school, and a subset of participants (N = 117, Mage = 13.59 years) completed a neuroimaging task in which they viewed peer faces from their social networks. We revealed two neural processes by which adolescents track social preference: (1) the fusiform face area, an important region for early visual perception and social categorization, simultaneously represented both peers high in social preference and low in social preference; (2) the dorsolateral prefrontal cortex (DLPFC), which was differentially engaged in tracking peers high and low in social preference. No regions specifically tracked peers high in popularity and only the inferior parietal lobe, temporoparietal junction, midcingulate cortex and insula were involved in tracking unpopular peers. This is the first study to examine the neural circuits that support adolescents' perception of peer-based social networks. These findings identify the neural processes that allow youths to spontaneously keep track of peers' social value within their social network.


Assuntos
Comportamento do Adolescente , Hierarquia Social , Humanos , Adolescente , Grupo Associado , Instituições Acadêmicas , Rede Social
5.
Mol Carcinog ; 62(11): 1731-1744, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37589446

RESUMO

The cell cycle, a pivotal regulator of cell proliferation, can be significantly influenced by the phosphatase and tensin homolog (PTEN)/AKT signaling pathway's modulation of cyclin-related proteins. In our study, we discovered the crucial role of EEF1E1 in this process, as it appears to downregulate PTEN expression. Furthermore, our findings affirmed that EEF1E1 modulates downstream cell cycle-related proteins by suppressing the PTEN/AKT pathway. Cell cycle assay results revealed that EEF1E1 downregulation stunted the advancement of glioma cells in both the G1 and S phases. A suite of assays-Cell Counting Kit-8, colony formation, and ethyl-2'-deoxyuridine-substantiated that the EEF1E1 downregulation markedly curtailed glioma proliferation. We further validated this phenomenon through animal studies and coculture experiments on brain slices. Our comprehensive investigation indicates that EEF1E1 knockdown can effectively inhibit the glioma cell proliferation by regulating the cell cycle via the PTEN/AKT signaling pathway. Consequently, EEF1E1 emerges as a potential therapeutic target for glioma treatment, signifying critical clinical implications.

6.
Cancer Med ; 12(15): 16098-16107, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37326317

RESUMO

BACKGROUND: Perioperative chemotherapy/chemoradiation is standard in esophageal/gastric/gastroesophageal junction (GEJ) adenocarcinoma, immune checkpoint inhibitors (ICI) effect in setting of metastatic and postoperatively. This study is to assess ICI + chemotherapy perioperatively. METHODS: Patients with locally advanced (T1N1-3M0 or T2-3NanyM0) potentially resectable esophageal/gastric/GEJ adenocarcinoma by PET/EUS/CT and staging-laparoscopy, were treated preoperative 4 cycles mFOLFOX6 (Oxaliplatin 85 mg/m2 /Leucovorin 400 mg/m2 /5-FU bolus 400 mg/m2 then infusion 2400 mg/m2 for 46 h q2weeks) and 3 cycles pembrolizumab (200 mg q3week). Those without distal disease post-neoadjuvant and eligible for resection underwent surgery. Postoperative treatment was initiated at 4-8 weeks with 4 cycles mFOLFOX and 12 cycles pembrolizumab. The primary objective is pathological response (ypRR with tumor regression score, TRS ≤2). The expression of ICI-related markers PD-L1 (CPS), CD8, and CD20 were analyzed before and after preoperative therapy. RESULTS: Thirty-seven patients completed the preoperative treatment. Twenty-nine patients had curative R0 resection. 6/29 (21%; 95% CI: 0.08-0.40) achieved ypCR with TRS 0 in resected patients. 26/29 (90%; 95% CI: 0.73-0.98) had ypRR with TRS ≤2. Twenty-six patients finished adjuvant therapy with a median 36.3-month follow-up. Three patients had recurrence/metastatic disease (at 9-, 10-, 22 months enrollment) with one dead at 23 months, and two are still alive at 28 and 36.5 months. The remaining (23/26) are free of disease with 3 years DFS of 88.5% and 3 years OS of 92.3%. There were no unexpected toxicities. Preoperative ICI + chemotherapy enhanced immune responses significantly with increasing expression of PD-L1 (CPS ≥10, p = 0.0078) and CD8 (>5%, p = 0.0059). CONCLUSIONS: The perioperative pembrolizumab and mFOLFOX combination in resectable esophageal/gastric/GEJ adenocarcinoma is very effective with 90% ypRR, 21% ypCR, and impressive long-time survival benefits.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Antígeno B7-H1 , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Terapia Neoadjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
7.
Hum Brain Mapp ; 44(10): 3972-3985, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37227026

RESUMO

Adolescence is marked by increased peer influence on risk taking; however, recent literature suggests enormous individual variation in peer influence susceptibility to risk-taking behaviors. The current study uses representation similarity analysis to test whether neural similarity between decision-making for self and peers (i.e., best friends) in a risky context is associated with individual differences in self-reported peer influence susceptibility and risky behaviors in adolescents. Adolescent participants (N = 166, Mage = 12.89) completed a neuroimaging task in which they made risky decisions to receive rewards for themselves, their best friend, and their parents. Adolescent participants self-reported peer influence susceptibility and engagement in risk-taking behaviors. We found that adolescents with greater similarity in nucleus accumbens (NACC) response patterns between the self and their best friend reported greater susceptibility to peer influence and increased risk-taking behaviors. However, neural similarity in ventromedial prefrontal cortex (vmPFC) was not significantly associated with adolescents' peer influence susceptibility and risk-taking behaviors. Further, when examining neural similarity between adolescents' self and their parent in the NACC and vmPFC, we did not find links to peer influence susceptibility and risk-taking behaviors. Together, our results suggest that greater similarity for self and friend in the NACC is associated with individual differences in adolescents' peer influence susceptibility and risk-taking behaviors.


Assuntos
Comportamento do Adolescente , Influência dos Pares , Humanos , Adolescente , Criança , Amigos , Autorrelato , Núcleo Accumbens/diagnóstico por imagem , Assunção de Riscos
8.
Vascul Pharmacol ; 148: 107143, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682595

RESUMO

BACKGROUND: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD). METHODS: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm. RESULTS: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1ß in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups. CONCLUSIONS: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. (clinicaltrials.gov # NCT03649711).


Assuntos
Insuficiência Renal Crônica , Trombose , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Ticlopidina/efeitos adversos , Adenosina , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento
9.
Cell Rep Med ; 4(2): 100916, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36702123

RESUMO

This is the phase Ib part of the phase I/II CAMILLA trial evaluating cabozantinib plus durvalumab in advanced chemo-refractory proficient mismatch repair or microsatellite stable (pMMR/MSS) gastrointestinal malignancies including gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma, colorectal cancer (CRC), and hepatocellular carcinoma (HCC). Thirty-five patients are enrolled. There are no observed dose-limiting toxicities during dose escalation. The overall grade 3/4 treatment-related adverse event rate is 34%. Among evaluable patients (n = 30), the objective response rate (ORR) is 30%, disease control rate (DCR) 83.3%, 6-month progression-free survival (PFS) 36.7%, median PFS 4.5 months, and median overall survival (OS) 8.7 months. Responses are seen in 4 of 17, 3 of 10, and 2 of 3 patients with CRC, G/GEJ/E adenocarcinoma, and HCC, respectively. Participants with a PD-L1 combined positive score (CPS) ≥5 have numerically higher ORR, PFS, and OS. Cabozantinib plus durvalumab demonstrates a tolerable safety profile and potential efficacy in previously treated advanced pMMR/MSS gastrointestinal malignancies.


Assuntos
Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia
10.
J Cogn Neurosci ; 35(4): 715-735, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36638228

RESUMO

Faces can be represented at a variety of different subordinate levels (e.g., race) that can become "privileged" for visual recognition in perceivers and is reflected as patterns of biases (e.g., own-race bias). The mechanisms encoding privileged status are likely varied, making it difficult to predict how neural systems represent subordinate-level biases in face processing. Here, we investigate the neural basis of subordinate-level representations of human faces in the ventral visual pathway, by leveraging recent behavioral findings indicating the privileged nature of peer faces in identity recognition for adolescents and emerging adults (i.e., ages 18-25 years). We tested 166 emerging adults in a face recognition paradigm and a subset of 31 of these participants in two fMRI task paradigms. We showed that emerging adults exhibit a peer bias in face recognition behavior, which indicates a privileged status for a subordinate-level category of faces that is not predicted based on experience alone. This privileged status of peer faces is supported by multiple neural mechanisms within the ventral visual pathway, including enhanced neural magnitude and neural size in the neural size in the fusiform area (FFA1), which is a critical part of the face-processing network that fundamentally supports the representations of subordinate-level categories of faces. These findings demonstrate organizational principles that the human ventral visual pathway uses to privilege relevant social information in face representations, which is essential for navigating human social interactions. It will be important to understand whether similar mechanisms support representations of other subordinate-level categories like race and gender.


Assuntos
Mapeamento Encefálico , Reconhecimento Facial , Adolescente , Humanos , Adulto , Adulto Jovem , Reconhecimento Psicológico , Reconhecimento Visual de Modelos
11.
Chest ; 163(4): 861-869, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36470416

RESUMO

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. RESULTS: Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC % predicted was found after 12 months of treatment compared with the potential 12-month response without treatment (+3.90%; P ≤ .001; 95% CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted also improved at 12 months (+4.53%; P ≤ .001; 95% CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. INTERPRETATION: Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings.


Assuntos
Artrite Reumatoide , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Azatioprina/uso terapêutico , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Capacidade Vital
12.
Kidney360 ; 3(8): 1374-1383, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36176642

RESUMO

Background: Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients. Methods: In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed. Results: Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel. Conclusions: More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.


Assuntos
Falência Renal Crônica , Antagonistas do Receptor Purinérgico P2Y , Idoso , Clopidogrel/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Falência Renal Crônica/induzido quimicamente , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Ticagrelor
13.
Behav Res Methods ; 54(6): 3071-3084, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35194750

RESUMO

The Cambridge Face Memory Test (CFMT) is one of the most used assessments of face recognition abilities in the science of face processing. The original task, using White male faces, has been empirically evaluated for psychometric properties (Duchaine & Nakayama, 2006), while the longer and more difficult version (CFMT+; Russell et al., 2009) has not. Critically, no version exists using female faces. Here, we present the Female Cambridge Face Memory Test - Long Form (F-CFMT+) and evaluate the psychometric properties of this task in comparison to the Male Cambridge Face Memory Test - Long Form (M-CFMT+). We tested typically developing emerging adults (18 to 25 years old) in both Cambridge face recognition tasks, an old-new face recognition task, and a car recognition task. Results indicate that the F-CFMT+ is a valid, internally consistent measure of unfamiliar face recognition that can be used alone or in tandem with the M-CFMT+ to assess recognition abilities for young adult White faces. When used together, performance on the F-CFMT+ and M-CFMT+ can be directly compared, adding to the ability to understand face recognition abilities for different kinds of faces. The two tasks have high convergent validity and relatively good divergent validity with car recognition in the same task paradigm. The F-CFMT+ will be useful to researchers interested in evaluating a broad range of questions about face recognition abilities in both typically developing individuals and those with atypical social information processing abilities.


Assuntos
Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Adulto
14.
Kidney360 ; 3(12): 2036-2047, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36591354

RESUMO

Background: Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stage 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT; aspirin 81 mg/d plus P2Y12 inhibitor). Methods: In a mechanistic clinical trial, we compared platelet activation markers (aggregation and surface receptor expression), circulating platelet-leukocyte aggregates, leukocyte composition (monocyte subtypes and CD11b surface expression), and plasma cytokine profile (45 analytes) of non-CKD controls (n=26) and CKD outpatients (n=48) with a glomerular filtration rate (GFR) <30 ml/min per 1.73 m2 on 2 weeks of DAPT. Results: Patients with CKD demonstrated a reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classic monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine (all P<0.05). There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation in both groups, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in PDGF levels in all CKD individuals, reductions in IL-1ß and TNF-α levels in select CKD individuals, and no change in a number of other cytokines. Significant positive correlations existed for baseline IL-1ß, PDGF, and TNF-α levels with older age, and for baseline TNF-α levels with presence of diabetes mellitus and worse albuminuria. Mean change in IL-1ß and PDGF levels on DAPT positively correlated with younger age, mean change in TNF-α levels with higher GFR, and mean changes in PDGF, and TRAIL levels correlated with worse albuminuria. Minimum spanning trees plot of cytokines showed platelet-derived CD40L had a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1ß and PDGF were tightly correlated with other cytokines, with IL-1ß as the hub cytokine. Conclusions: Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet-derived cytokines were one of the central cytokines in patients with CKD that were tightly correlated with others. DAPT had multifaceted effects on thromboinflammation, suggesting that there is platelet-dependent and -independent inflammation in stage 4 or 5 CKD.


Assuntos
Insuficiência Renal Crônica , Trombose , Humanos , Albuminúria/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/tratamento farmacológico , Fator de Necrose Tumoral alfa
15.
Am Psychol ; 77(9): 1067-1081, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36595405

RESUMO

In this review, we seek to challenge negative stereotypes of adolescence and unpack the many ways that the developing brain contributes to positive development during the adolescent years. In particular, we will show that risk-taking is not inevitable and risks can be highly adaptive and positive; adolescents are not overly self-centered but engage in other-oriented prosocial behaviors in remarkable ways; adolescents are not only susceptible to negative peer influence but can resist negative peer influence and conform more to positive peer influence; and adolescents do not orient away from the family, but the family remains a constant and important source of influence into adolescence. We outline considerations that researchers can use to reframe their research questions to provide a more balanced perspective on adolescent development, thereby promoting positive development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Comportamento do Adolescente , Comportamento Social , Humanos , Adolescente , Desenvolvimento do Adolescente , Encéfalo , Altruísmo
16.
Hosp Pharm ; 56(5): 451-461, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34720145

RESUMO

Background: Pharmacy administrative claims data remain an accessible and efficient source to measure medication adherence for frequently hospitalized patient populations that are systematically excluded from the landmark drug trials. Published pharmacotherapy studies use medication possession ratio (MPR) and proportion of days covered (PDC) to calculate medication adherence and usually fail to incorporate hospitalization and prescription overlap/gap from claims data. To make the cacophony of adherence measures clearer, this study created a refined hospital-adjusted algorithm to capture pharmacotherapy adherence among patients with end-stage renal disease (ESRD). Methods: The United States Renal Data System (USRDS) registry of ESRD was used to determine prescription-filling patterns of those receiving new prescriptions for oral P2Y12 inhibitors (P2Y12-I) between 2011 and 2015. P2Y12-I-naïve patients were followed until death, kidney transplantation, discontinuing medications, or loss to follow-up. After flagging/censoring key variables, the algorithm adjusted for hospital length of stay (LOS) and medication overlap. Hospital-adjusted medication adherence (HA-PDC) was calculated and compared with traditional MPR and PDC methods. Analyses were performed with SAS software. Results: Hospitalization occurred for 78% of the cohort (N = 46 514). The median LOS was 12 (interquartile range [IQR] = 2-34) days. MPR and PDC were 61% (IQR = 29%-94%) and 59% (IQR = 31%-93%), respectively. After applying adjustments for overlapping coverage days and hospital stays independently, HA-PDC adherence values changed in 41% and 52.7% of the cohort, respectively. When adjustments for overlap and hospital stay were made concurrently, HA-PDC adherence values changed in 68% of the cohort by 5.8% (HA-PDC median = 0.68, IQR = 0.31-0.93). HA-PDC declined over time (3M-6M-9M-12M). Nearly 48% of the cohort had a ≥30 days refill gap in the first 3 months, and this increased over time (P < .0001). Conclusions: Refill gaps should be investigated carefully to capture accurate pharmacotherapy adherence. HA-PDC measures increased adherence substantially when adjustments for hospital stay and medication refill overlaps are made. Furthermore, if hospitalizations were ignored for medications that are included in Medicare quality measures, such as Medicare STAR program, the apparent reduction in adherence might be associated with lower quality and health plan reimbursement.

17.
Kidney Int Rep ; 6(9): 2381-2391, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34514199

RESUMO

INTRODUCTION: Although oral P2Y12 inhibitors (P2Y12-Is) are one of the most commonly prescribed medication classes in patients with end stage kidney disease on dialysis (ESKD), scarce data exist regarding their benefits and risks. METHODS: We compared effectiveness and safety of clopidogrel, prasugrel, and ticagrelor in a longitudinal study using the United States Renal Data System registry of Medicare beneficiaries with ESKD. Individuals who filled new P2Y12-I prescriptions between 2011 and 2015 were included and followed until death or censoring. The primary exposure variable was P2Y12-I assignment. The primary outcome variable was death. Secondary outcomes included cardiovascular (CV) death, coronary revascularization, and gastrointestinal (GI) hemorrhage. Survival analyses were performed after propensity matching. RESULTS: Of 44,619 patients with ESKD who received P2Y12-Is, 95% received clopidogrel (n = 42,523), 3% prasugrel (n = 1205), and 2% ticagrelor (n = 891). To balance baseline differences, propensity-matching was performed: 1:6 for prasugrel (n = 1189) versus clopidogrel (n = 7134); 1:4 for ticagrelor (n = 880) versus clopidogrel (n = 3520); and 1:1 for ticagrelor versus prasugrel (n = 880). Prasugrel was associated with a reduced risk for death versus clopidogrel and ticagrelor (adjusted hazard ratio [HR] = 0.82; 95% CI: 0.73-0.93 and 0.78; 95% CI: 0.64-0.95). Compared with clopidogrel, prasugrel reduced risk for coronary revascularization (HR = 0.91; 95% CI: 0.86-0.96). There were no differences in GI hemorrhage between P2Y12-Is. CONCLUSION: In patients with ESKD, prasugrel compared with others reduced risk of death possibly by reducing risk for coronary revascularizations and without worsening gastrointestinal hemorrhage. Future trials are imperative to compare efficacy and safety of P2Y12-Is in patients with ESKD.

18.
Urology ; 157: 51-56, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34186132

RESUMO

OBJECTIVE: To demonstrate the distribution and impact of fellowship-trained andrology and/or sexual medicine urological specialists (FTAUS) on resident in-service examination (ISE) performance. METHODS: Residency program websites were accessed to create a database of FTAUS in the United States between 2007 and 2017. This database was reviewed by three separate FTAUS and cross referenced with membership lists to the Sexual Medicine of North America Society and the Society for the Study of Male Reproduction. De-identified ISE scores were obtained from the American Urological Association from 2007-2017 and scores from trainees at programs with a FTAUS were identified for comparison. Resident performance was analyzed using a linear model of the effect of a resident being at a program with an FTAUS, adjusting for post-graduate year. RESULTS: ISE data from 13,757 residents were obtained for the years 2007-2017. The number of FTAUS in the United States increased from 40-102 during this study period. Mean raw scores on the "Sexual Dysfunction, Endocrinopathy, Fertility Problems" (SDEFP) section of the ISE ranged from 52.1% ± 17.7% to 65.7% ± 16% (mean ± SD). Throughout the study period, there was no difference in performance within the SDEFP section (P < .01). Residents at a program with a FTAUS answered 0.95% more questions correctly in the SDEFP than those without a FTAUS (P < .001). For these residents, there was an improvement of approximately 0.66% on the percentage of questions answered correctly on the ISE overall (P < .001). Performance improved significantly as residents progressed from PGY-2-PGY-5. CONCLUSION: There is a small but statistically significant improvement in overall ISE and SDEFP sub-section performance.


Assuntos
Andrologia/educação , Competência Clínica , Avaliação Educacional , Bolsas de Estudo , Sociedades Médicas , Estados Unidos , Urologia
19.
Oncol Nurs Forum ; 47(2): 203-212, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078618

RESUMO

OBJECTIVES: To test the feasibility of adding driving simulation tasks to measure visuospatial ability and processing speed to an existing neurocognitive battery for breast cancer survivors (BCSs). SAMPLE & SETTING: 38 BCSs and 17 healthy controls from a cross-sectional pilot study conducted at the University of Kansas Medical Center. METHODS & VARIABLES: Exploratory substudy measuring pupillary response, visuospatial ability, and processing speed during two 10-minute driving simulations (with or without n-back testing) in a sample of BCSs with self-reported cognitive complaints and healthy controls. RESULTS: Feasibility of measurement of pupillary response during driving simulation was demonstrated. No between-group differences were noted for pupillary response during driving simulation. BCSs had greater visuospatial ability and processing speed performance difficulties than healthy controls during driving simulation without n-back testing and slower n-back response time. IMPLICATIONS FOR NURSING: Preliminary evidence showed a possible link between cancer/treatment on visuospatial ability and processing speed in BCSs.


Assuntos
Condução de Veículo , Neoplasias da Mama/complicações , Sobreviventes de Câncer , Cognição/fisiologia , Distúrbios Pupilares/diagnóstico , Distúrbios Pupilares/etiologia , Navegação Espacial/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Kansas , Pessoa de Meia-Idade , Projetos Piloto
20.
Cardiovasc Drugs Ther ; 33(5): 511-521, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31729588

RESUMO

BACKGROUND: Trends and clinical factors associated with prescribing choices for oral P2Y12 inhibitors (P2Y12-I) remain unknown for patients on chronic dialysis, i.e., with end-stage renal disease (ESRD). METHODS: From 2011-2014 U.S. Renal Data System registry, we identified 36,542 ESRD patients who received new prescriptions for P2Y12-I (median age 64.0 years and 54% males). Of the cohort, 93% were receiving hemodialysis and 7% on peritoneal dialysis. We analyzed trends and investigated clinical factors associated with specific P2Y12-I prescribed. RESULTS: Clopidogrel was prescribed for 95%, prasugrel for 3%, and ticagrelor for 2%. Clopidogrel was favored for those ≥75 years (18% of cohort). Compared to Caucasians, African Americans (36% of cohort) and Hispanics (19% of cohort) were less likely to receive prasugrel and ticagrelor (P<0.05). Patients receiving hemodialysis versus peritoneal dialysis were less likely to receive prasugrel over clopidogrel, adjusted odds ratio (aOR) 0.67 (0.55-0.82). Each additional year of dialysis decreased the odds of receiving prasugrel over clopidogrel, aOR 0.91 (0.85-0.98). History of atrial fibrillation reduced the odds of receiving ticagrelor or prasugrel over clopidogrel, aOR 0.69 (0.54-0.89) and 0.73 (0.60-0.89), respectively. Concomitant oral anticoagulant use was not associated with choice of P2Y12-I. Occurrence of non-ST segment elevation myocardial infarction or percutaneous coronary intervention within the 6-month period prior to the index date favored ticagrelor over prasugrel, aOR 1.31 (1.06-1.62) and 1.29 (1.01-1.66), respectively. However, prescribing trends favoring ticagrelor over prasugrel were not observed for deployment of drug-eluting, or multiple coronary stents. CONCLUSION: Between 2011 and 2014, clopidogrel remained the most common P2Y12-I whereas ticagrelor and prasugrel remained underutilized in ESRD patients. Prescribing practices for these drugs were based upon clinically approved indication for their use in the general population as well as perceived complexity of an ESRD patient including demographics, dialysis-related factors and comorbidities. Comparative effectiveness studies involving ESRD patients are needed to prove that ticagrelor and prasugrel are just as safe and effective as clopidogrel before clinicians can make informed decisions for choice of P2Y12-I in this patient population.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Clopidogrel/administração & dosagem , Falência Renal Crônica/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Padrões de Prática Médica/tendências , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Diálise Renal , Ticagrelor/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Tomada de Decisão Clínica , Clopidogrel/efeitos adversos , Prescrições de Medicamentos , Uso de Medicamentos/tendências , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Diálise Peritoneal , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Prevalência , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
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