Aim: Chronic cocaine use is associated with decreases in neuroactive steroid levels. These adaptations may contribute to continued cocaine use and high relapse risk in individuals with cocaine use disorder (CUD). Thus, this pilot study assessed chronic treatment with 2 supraphysiologic doses of the neuroactive steroid precursor pregnenolone (PREG, 300 mg/day; 500 mg/day) to boost endogenous neuroactive steroid levels and assess its impact on provoked craving and cocaine use outcomes in an 8-week trial in men and women with CUD.
View Article and Find Full Text PDFIntroduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials.
Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain.
Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months.
Background: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD blood test that incorporates the plasma Aβ42/40 ratio, ApoE proteotype, and age to identify the likelihood of brain amyloid plaques among cognitively impaired individuals being evaluated for Alzheimer's disease.
Purpose: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.
Methods: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.
The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS).
View Article and Find Full Text PDFImportance: The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology.
Objective: To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status.
Design, Setting, And Participants: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019.
Background: There is an unmet need for an accessible, less invasive, cost-effective method to facilitate clinical trial enrollment and aid in clinical Alzheimer's disease (AD) diagnosis. APOE genotype affects the clearance and deposition of amyloid-beta (Aβ) with APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis.
View Article and Find Full Text PDFBackground: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.
View Article and Find Full Text PDFPhysical activity, and likely the motivation for it, varies throughout the day. The aim of this investigation was to create a short assessment (CRAVE: Cravings for Rest and Volitional Energy Expenditure) to measure motivation states (wants, desires, urges) for physical activity and sedentary behaviors. Five studies were conducted to develop and evaluate the construct validity and reliability of the scale, with 1,035 participants completing the scale a total of 1,697 times.
View Article and Find Full Text PDFThe pace of clinical trial data generation and publication is an area of interest within clinical oncology; however, little is known about the dynamics and covariates of time to reporting (TTR) of trial results. To assess these, ClinicalTrials.gov was queried for phase three clinical trials for patients with metastatic solid tumors, and the factors associated with TTR from enrollment completion to publication were analyzed.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is a fatal disease characterized by increased mean pulmonary arterial pressure. Elevated plasma and lung concentrations of oxidized lipids, including 15-hydroxyeicosatetraenoic acid (15-HETE), have been demonstrated in patients with PAH and animal models. We previously demonstrated that feeding mice with 15-HETE is sufficient to induce pulmonary hypertension, but the mechanisms remain unknown.
View Article and Find Full Text PDFBackground: The incidence and magnitude of indicators of radiographic response of pancreatic cancer to systemic chemotherapy and (chemo)radiation administered prior to anticipated pancreatectomy are unclear.
Methods: Sequential computed tomography scans of 226 patients with localized pancreatic cancer who received chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) or gemcitabine and nanoparticle albumin-bound paclitaxel (GA) with or without (chemo)radiation and who subsequently underwent surgery with curative intent from January 2010 to December 2018 at The University of Texas MD Anderson Cancer Center and Verona University Hospital were re-reviewed and compared.
Results: Overall, 141 patients (62%) received FOLFIRINOX, 70 (31%) received GA, and 15 (7%) received both; 164 patients (73%) received preoperative (chemo)radiation following chemotherapy and prior to surgery; and 151 (67%), 70 (31%), and 5 (2%) patients had Response Evaluation Criteria in Solid Tumors (RECIST) stable disease, partial response, and progressive disease, respectively.
Memory for prior drinking experiences may powerfully drive later alcohol use in familiar drinking contexts, yet we know little about what patients with alcohol use disorder (AUD) remember of alcohol-related episodes. Although animal and theoretical models of addiction emphasize the importance of different memory systems for understanding maladaptive use, clinical research parsing what AUD patients remember from alcohol-related episodes is lacking. The current study applied a novel memory task in which moderate drinkers (N = 30) and treatment-seeking individuals with alcohol use disorder (AUD: N = 29) encoded associations between photographs of objects (alcoholic beverages and neutral items) and photographs of neutral scenes.
View Article and Find Full Text PDFThe efficacy of chemotherapy is reduced by dysfunctional tumor vasculature, which may limit chemotherapy delivery to tumors. Preclinical studies have shown that moderate aerobic exercise improves tumor vascular function and increases chemotherapy efficacy in mouse models, but the effect of exercise on human tumor vasculature has not yet been determined. Here, we demonstrate that exercise remodels the tumor vasculature, accelerates the regression, and delays the regrowth of pancreatic ductal adenocarcinoma in a patient-derived xenograft mouse model treated with gemcitabine.
View Article and Find Full Text PDFBackground: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs).
Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs.
Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE.
Background: Binding of insulin-like growth factor-I (IGF-1) to its receptor (IGF-1R) initiates downstream signals that activate PI3K/Akt/mTOR and MEK/Erk pathways, which stimulate cancer cell proliferation and induce drug resistance. Cross talk between IGF-1R and epidermal growth factor receptor (EGFR) mediates resistance to anti-EGFR agents. We studied safety, tolerability, and outcomes of MK-0646, IGF-1 monoclonal antibody, in combination with gemcitabine (G) ± erlotinib (E) in metastatic pancreatic cancer.
View Article and Find Full Text PDFBackground: Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples.
View Article and Find Full Text PDFO1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y.
View Article and Find Full Text PDFObjective: We previously reported that hemopexin (Hx), a heme scavenger, is significantly increased and associated with proinflammatory high-density lipoprotein under atherogenic conditions. Although it is established that Hx together with macrophages plays a role in mitigating oxidative damage, the role of Hx in the development of atherosclerosis is unknown.
Approach And Results: We used Hx and apoE double-knockout mice (HxE(-/-)) to determine the role of Hx in the development of atherosclerosis.
Pulmonary arterial hypertension (PAH) is characterized by abnormal elaboration of vasoactive peptides, endothelial cell dysfunction, vascular remodeling, and inflammation, which collectively contribute to its pathogenesis. We investigated the potential for high-density lipoprotein (HDL) dysfunction (i.e.
View Article and Find Full Text PDFThe effects of vitamin E on cardiovascular and bone health are conflicting with beneficial and detrimental findings reported. To investigate this further, we carried out a cross-sectional study to determine the relationship between circulating concentrations of the 2 vitamin E isomers, α- and γ-tocopherol (TP) with bone turnover and arterial stiffness. Two hundred and seventy eight post-menopausal women with mean age [SD] 60.
View Article and Find Full Text PDFCancer Chemother Pharmacol
September 2015
Purpose: Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known.
Methods: For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated.
Purpose: Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab.
View Article and Find Full Text PDFBackground: Pulmonary arterial hypertension is a chronic lung disease associated with severe pulmonary vascular changes. A pathogenic role of oxidized lipids such as hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids is well established in vascular disease. Apolipoprotein A-I mimetic peptides, including 4F, have been reported to reduce levels of these oxidized lipids and improve vascular disease.
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