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ObjectiveTo explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).MethodsThis is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome.ResultsParticipants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p < 0.0001), were more likely to be male (75.3% vs 57.0%; p < 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p < 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores.ConclusionsPersons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding.Clinicaltrialsgov identifierNCT00449865.

The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months. Targeted therapy is based on the somatic mutation theory, which has some paradoxes and limitations. While efforts of targeted therapy must continue, we must study newer approaches that could advance therapy and affordability for patients. This work briefly overviews how cancer therapy has evolved from cytotoxic chemotherapy to current molecular-targeted therapy. The limitations of the one-target, one-drug approach considering cancer as a robust system and the basis for multitargeting approach with polypharmacotherapy using repurposing drugs. Multitargeted polypharmacotherapy for cancer with repurposed drugs should be systematically investigated in preclinical and clinical studies. Remarkably, most of these proposed drugs already have a long history in the clinical setting, and their safety is known. In principle, the risk of their simultaneous administration should not be greater than that of a first-in-human phase I study as long as the protocol is developed with strict vigilance to detect early possible side effects from their potential interactions. Research on cancer therapy should go beyond the prevailing paradigm targeted therapy. [ABSTRACT FROM AUTHOR]

BackgroundThe effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected.ObjectiveThe aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD.MethodsA non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life.ResultsThe outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine.ConclusionThis observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy.

ImportanceThere are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies.ObjectiveTo determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.Design, setting, and patientsThe Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.InterventionsParticipants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).Main outcomes and measuresThe primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes.ResultsThe trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P

Objective: To examine the associations between sensation seeking and ever and current e-cigarette use in Texas young adults (18-29 years old). Current cigarette use was examined as a potential effect modifier of the associations. Participants: Participants included college students enrolled in four-year and two-year colleges in four metropolitan areas in Texas (n = 5,418) who completed the survey between November 2014 and February 2015. Methods: This cross-sectional study utilized mixed effects logistic regression to determine the associations between mean sensation seeking scores and ever and current e-cigarette use after controlling for covariates. Results: After controlling for covariates, significant associations between sensation seeking and both ever and current e-cigarette use were observed; however, these associations were significant for noncurrent smokers only (adjusted odds rations [AOR] = 1.55, 95% confidence interval (CI) = 1.39, 1.73; AOR = 1.82, 95% CI = 1.54, 2.15, respectively). Conclusions: Sensation seeking is an important factor in identifying college students who may be at increased risk for e-cigarette use behaviors.

The aim to access linked tetravanadate [V4O12]4− anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4′-dimethioxy-2,2′-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4− anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV–Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium–copper(II) systems. [ABSTRACT FROM AUTHOR]

This study examined the association between having been bullied at school during the past 6 months ("bullied status") and not meeting physical activity (PA) recommendations of 60 minutes of daily PA during the past week among 8th- and 11th-grade Texas adolescents. Multiple logistic regression analysis was conducted to examine this association, adjusted for weight status, grade, race/ethnicity, and stratified by gender; furthermore, a significant interaction was found between bullied status and weight status. Results are presented by interaction status. Results indicated that overweight girls who reported never being bullied, as well as those who reported being bullied more than twice, had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (adjusted odds ratio [AOR] = 2.12, 95% confidence interval [CI: 1.12, 3.99]; AOR = 9.18, 95% CI [2.26, 37.27], respectively). Obese girls who were bullied once or twice had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (AOR = 2.89, 95% CI [1.06, 7.89]). Overweight boys who reported never being bullied had lower odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 0.62, 95% CI [0.39, 0.97]). Conversely, obese boys who were bullied once or twice reported higher odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 3.61, 95% CI [1.22, 10.67]). Findings from this study indicate that the association between bullied status and meeting PA recommendations is complex and may differ by gender and the interaction between bullied status and weight status.

Introduction Hispanic immigrants are more likely to breastfeed than are Hispanics born in the US, in part due to their acculturation. This paper aims to systematically review the existing literature on the association between acculturation and Hispanics' breastfeeding behaviors. Methods The systematic search used major databases such as Medline and PubMed, and it followed the PRISMA checklist. The scientific quality of the studies was rated using the Quality Assessment Tool for Quantitative Studies. Results We identified 1943 potential citations, of which 18 studies met the eligibility criteria. Overall, while 13 studies suggested that high-acculturated Hispanics were less likely to breastfeed compared with low-acculturated, five studies did not find significant evidence of such an association. Moreover, 12 studies used a static measure or a linear scale, which is not optimal; only three studies utilized bi/multidimensional scales to assess acculturation. Intention to breastfeed was examined in six studies, but the results were inconsistent. Breastfeeding initiation was examined in 11 studies, and two out of eight studies that examined breastfeeding duration, specifically analyzed exclusive breastfeeding at 6 months. Discussion Our results agree with the general hypothesis that higher acculturation is inversely related to breastfeeding rates, independently of income. Researchers used different methodologies to study acculturation and breastfeeding practices, limiting our ability to reach more detailed conclusions. Owing to the lack of a standard methodology for measuring acculturation, future studies should utilize bi/multidimensional scales when studying breastfeeding, in particular, in relation to breastfeeding intention and exclusive breastfeeding at 6 months; preferably according to Hispanic subgroups., Author(s): Galya Bigman [sup.1] , Anna V. Wilkinson [sup.1] , Adriana Pérez [sup.2] , Nuria Homedes [sup.3] Author Affiliations: (Aff1) 0000 0000 9206 2401, grid.267308.8, Epidemiology, Human Genetics and Environmental [...]