المؤلفون: Jessica G. Woo, John T. Melchior, Debi K. Swertfeger, Alan T. Remaley, Ebrima A. Sise, Fatou Sosseh, Jeffrey A. Welge, Andrew M. Prentice, W. Sean Davidson, Sophie E. Moore, Laura A. Woollett

المصدر: Lipids in Health and Disease, Vol 22, Iss 1, Pp 1-12 (2023)

مصطلحات موضوعية: High-density lipoprotein, Low-density lipoprotein, Triglyceride-rich lipoprotein, Proteomics, Subspecies, Nutritional diseases. Deficiency diseases, RC620-627

الوصف: Abstract Background Lipoprotein subfraction concentrations have been shown to change as gestation progresses in resource-rich settings. The objective of the current study was to evaluate the impact of pregnancy on different-sized lipoprotein particle concentrations and compositions in a resource-poor setting. Method Samples were collected from pregnant women in rural Gambia at enrollment (8–20 weeks), 20 weeks, and 30 weeks of gestation. Concentrations of different-sized high-density, low-density, and triglyceride-rich lipoprotein particles (HDL, LDL, and TRL, respectively) were measured by nuclear magnetic resonance in 126 pooled plasma samples from a subset of women. HDL was isolated and the HDL proteome evaluated using mass spectroscopy. Subfraction concentrations from women in The Gambia were also compared to concentrations in women in the U.S. in mid gestation. Results Total lipoprotein particles and all-sized TRL, LDL, and HDL particle concentrations increased during gestation, with the exception of medium-sized LDL and HDL particles which decreased. Subfraction concentrations were not associated with infant birth weights, though relationships were found between some lipoprotein subfraction concentrations in women with normal versus low birth weight infants (

وصف الملف: electronic resource

Relation: https://doaj.org/toc/1476-511X

URL الوصول: https://doaj.org/article/702dcf393a3a45b7ba1c7e29b250bfc0

المؤلفون: Chen Chen, Bin Huang, Michal Kouril, Jinzhong Liu, Hang Kim, Siva Sivaganisan, Jeffrey A. Welge, Melissa P. DelBello

المصدر: Frontiers in Computer Science, Vol 5 (2023)

مصطلحات موضوعية: application programming interface (API), BART, comparative effectiveness research (CER), averaged treatment effect (ATE), conditional ATE (CATE), Gaussian process (GP), Electronic computers. Computer science, QA75.5-76.95

الوصف: IntroductionMethods and tools evaluating treatment effect have been primarily developed for binary type of treatment. Yet, treatment is rarely binary outside the experimental setting, varies by dosage, frequency and time. Treatment is routinely adjusted, initiated or stopped when being administered over a period of time.MethodsBoth Gaussian Process (GP) regression and Bayesian additive regression tree (BART) have been used successfully for handling complex setting involving time-varying treatments that is either adaptive or non-adaptive. Here, we introduce an application programming interface (API) that implements both BART and GP for estimating averaged treatment effect (ATE) and conditional averaged treatment (CATE) for the two-stage time-varying treatment strategies.ResultsWe provide two real applications for evaluating comparative effectiveness of time-varying treatment strategies. The first example evaluates an early aggressive treatment strategies for caring children with newly diagnosed Juvenile Idiopathic Arthritis (JIA). The second evaluates the persistent per-protocol treatment effectiveness in a large randomized pragmatic trial. The examples demonstrate the use of the API calling from R and Python, for handling both non-adaptive or adaptive treatments, with presences of partially observed or missing data issues. Summary tables and interactive figures of the results are downloadable.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fcomp.2023.1183380/full; https://doaj.org/toc/2624-9898

URL الوصول: https://doaj.org/article/150523cee15943ddb46478a8748eb300

المؤلفون: Jhanvi N. Desai, Abigail R. Muccilli, Luis E. Tron Esqueda, Jeffrey A. Welge, PhD, Andrew B. Norman, PhD

المصدر: Current Therapeutic Research, Vol 99, Iss , Pp 100727- (2023)

مصطلحات موضوعية: Addiction, Compulsion zone, Satiety threshold, Priming threshold, Remission threshold, Therapeutics. Pharmacology, RM1-950

الوصف: ABSTRACT: Background: Many features of self-administration behavior may be explained by reference to the properties of schedules of reinforcement. Schedules alter the probability of a behavior being reinforced and thereby increase, or decrease, the frequency of the behavior and fixed ratio (FR) magnitude reportedly alters the rate of responding to cocaine. A pharmacokinetic/pharmacodynamic interaction theory states that lever-pressing behavior is induced only when cocaine levels in the body are above the priming/remission threshold and below the satiety threshold—a range termed the compulsion zone. This theory successfully explains cocaine self-administration in rats on a progressive ratio and the FR1 schedule. Objectives: To determine the effects of high FR magnitude on the rate of self-administration of cocaine and the rate of lever-pressing behavior when cocaine levels are within the compulsion zone. Methods: Rats acquired cocaine self-administration on an FR1 schedule and then were switched to sessions that started with FR1 and then FR 5, 10, 20, or 50. An only FR1 session was run each week between FR1/FR50 sessions and then only FR1 sessions were conducted for several weeks. Results: Interinjection intervals at a unit dose of 3 µmol/kg were regular at both FR1 and FR50 but were longer by the time required to complete the 50 presses. When responding by rats was maintained under an FR50 schedule of cocaine presentations, compared to baseline FR1 sessions, dramatic increases in the number of lever-presses were observed after access to cocaine was terminated, a previously unreported finding. However, lever-pressing occurred only when cocaine levels were in the compulsion zone, and this duration was unchanged. The increase in lever-pressing persisted for weeks. Interinjection intervals at FR1 were not altered after exposure to FR50. Conclusions: Although previously considered key to understanding the regulation of cocaine self-administration behavior, FR magnitude simply increased interinjection intervals by the time required to complete 50 lever-presses. The dramatic increase in the rate of lever-pressing was caused by the high FR schedule rather than cocaine. The utility of the schedule-induced increase in the rate of lever-pressing is unclear. The compulsion zone theory provides a rational pharmacological basis for understanding cocaine self-administration behavior.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S0011393X2300036X; https://doaj.org/toc/0011-393X

URL الوصول: https://doaj.org/article/162c5cc4f70c4e7fab430f250cfb9cd5

المؤلفون: Francisco Romo-Nava, Anna I. Guerdjikova, Nicole N. Mori, Frank A. J. L. Scheer, Helen J. Burgess, Robert K. McNamara, Jeffrey A. Welge, Carlos M. Grilo, Susan L. McElroy

المصدر: Frontiers in Nutrition, Vol 9 (2022)

مصطلحات موضوعية: binge eating, circadian, chronobiology, actigraphy, obesity, chronotype, Nutrition. Foods and food supply, TX341-641

الوصف: BackgroundEmerging research suggests that food intake timing, eating behavior and food preference are associated with aspects of the circadian system function but the role that the circadian system may play in binge eating (BE) behavior in humans remains unclear.ObjectiveTo systematically evaluate the evidence for circadian system involvement in BE behavior.MethodsSystematic searches of PubMed, EMBASE, and Scopus were performed for reports published from inception until May 2020 (PROSPERO Registration CRD42020186325). Searches were conducted by combining Medical Subject Headings related to the circadian system, BE behavior, and/or interventions. Observational and interventional studies in humans with BE behavior published in peer-review journals in the English language were included. Studies were assessed using quality and risk of bias tools (AXIS, ROB 2.0, or ROBINS).ResultsThe search produced 660 articles, 51 of which were included in this review. Of these articles, 46 were observational studies and 5 were interventional trials. Evidence from these studies suggests that individuals with BE behavior tend to have more food intake, more binge cravings, and more BE episodes later in the day. Hormonal and day/night locomotor activity rhythm disturbances may be associated with BE behavior. Furthermore, late diurnal preference (“eveningness”) was associated with BE behavior and chronobiological interventions that shift the circadian clock earlier (e.g., morning bright light therapy) were found to possibly decrease BE behavior. Substantive clinical overlap exists between BE and night eating behavior. However, there is a significant knowledge gap regarding their potential relationship with the circadian system. Limitations include the lack of studies that use best-established techniques to assess the chronobiology of BE behavior, heterogeneity of participants, diagnostic criteria, and study design, which preclude a meta-analytic approach.ConclusionCurrent evidence, although limited, suggests that the circadian system may play a role in the etiology of BE behavior. Further mechanistic studies are needed to fully characterize a potential role of the circadian system in BE behavior. A chronobiological approach to studying BE behavior may lead to identification of its neurobiological components and development of novel therapeutic interventions.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186325], identifier [CRD42020186325].

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fnut.2022.978412/full; https://doaj.org/toc/2296-861X

URL الوصول: https://doaj.org/article/7dbff6cff6944967a62fe6e6ea02c004

المؤلفون: Fabiano G. Nery, Sheela L. Masifi, Jeffrey R. Strawn, Luis R. Duran, Wade A. Weber, Jeffrey A. Welge, Caleb M. Adler, Stephen M. Strakowski, Melissa P. DelBello

المصدر: Brazilian Journal of Psychiatry, Vol 43, Iss 1, Pp 70-74 (2020)

مصطلحات موضوعية: Bipolar disorder, antidepressants, adverse events, functional magnetic resonance imaging, amygdala, Psychiatry, RC435-571

الوصف: Objective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. Results: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). Conclusions: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

وصف الملف: electronic resource

Relation: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462021000100013&tlng=en; http://www.scielo.br/pdf/rbp/v43n1/1516-4446-rbp-1516444620190803.pdf; https://doaj.org/toc/1809-452X

URL الوصول: https://doaj.org/article/19b4e1f5205f442782987619e348bade

المؤلفون: John T. Melchior, Debi K. Swertfeger, Jamie Morris, Scott E. Street, Carri R. Warshak, Jeffrey A. Welge, Alan T. Remaley, Janet M. Catov, W. Sean Davidson, Laura A. Woollett

المصدر: Journal of Lipid Research, Vol 62, Iss , Pp 100107- (2021)

مصطلحات موضوعية: dyslipidemia, nuclear magnetic resonance spectroscopy, lipoprotein, proteomics, mass spectrometry, pregnancy, Biochemistry, QD415-436

الوصف: Pregnancy is accompanied by significant physiological changes, which can impact the health and development of the fetus and mother. Pregnancy-induced changes in plasma lipoproteins are well documented, with modest to no impact observed on the generic measure of high density lipoprotein (HDL) cholesterol. However, the impact of pregnancy on the concentration and composition of HDL subspecies has not been examined in depth. In this prospective study, we collected plasma from 24 nonpregnant and 19 pregnant women in their second trimester. Using nuclear magnetic resonance (NMR), we quantified 11 different lipoprotein subspecies from plasma by size, including three in the HDL class. We observed an increase in the number of larger HDL particles in pregnant women, which were confirmed by tracking phospholipids across lipoproteins using high-resolution gel-filtration chromatography. Using liquid chromatography-mass spectrometry (LC-MS), we identified 87 lipid-associated proteins across size-speciated fractions. We report drastic shifts in multiple protein clusters across different HDL size fractions in pregnant females compared with nonpregnant controls that have major implications on HDL function. These findings significantly elevate our understanding of how changes in lipoprotein metabolism during pregnancy could impact the health of both the fetus and the mother.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S0022227521000894; https://doaj.org/toc/0022-2275

URL الوصول: https://doaj.org/article/5826d53782b841698497b93ac7f63d14

المؤلفون: William E. Hurford, Mark H. Eckman, Jeffrey A. Welge

المصدر: Data in Brief, Vol 32, Iss , Pp 106241- (2020)

مصطلحات موضوعية: Adult, Gamma-cyclodextrins, Meta-analysis, Neostigmine, Neuromuscular blocking agents, Sugammadex, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390

الوصف: This meta-analysis was conducted to define clinical efficacy and side effects (bradycardia and post-operative nausea and vomiting [PONV]) in trials comparing sugammadex with neostigmine or placebo for reversal of rocuronium-induced neuromuscular blockade in adult patients. A search of PubMed, Google Scholar, and Cochrane Library electronic databases identified 111 clinical trials for potential inclusion. We performed a meta-analysis of 32 studies that quantitatively compared the efficacy and side effects of sugammadex with either neostigmine or placebo in adult patients requiring general anesthesia. Analyzed outcomes were reversal time, anesthesia time, duration of stay in the post-anesthesia care unit (PACU), and the occurrence of bradycardia or PONV. Odds ratios and 95% confidence intervals (CI) were calculated for binary data. Mean differences and 95% CI were calculated for continuous outcome data. Meta-analyses were performed using random and fixed-effects models. Heterogeneity across studies was assessed using Cochran's Q test and the I2 statistic. Quantification of these outcomes can better inform anesthetists and health systems of the relative costs and benefits of the two reversal agents. This information also forms a basis for a comparative cost analysis in a co-submitted manuscript [1].

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2352340920311355; https://doaj.org/toc/2352-3409

URL الوصول: https://doaj.org/article/bde279c61a6743f5b154300c709971df

المؤلفون: Aleksey Porollo, Thomas M. Sesterhenn, Margaret S. Collins, Jeffrey A. Welge, Melanie T. Cushion

المصدر: mBio, Vol 5, Iss 6 (2014)

مصطلحات موضوعية: Microbiology, QR1-502

الوصف: ABSTRACT In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those in S. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed for P. carinii and P. jirovecii and extended to P. murina. All three Pneumocystis species showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known in S. pombe, four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol-pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC 3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were identified in the two rodent Pneumocystis genomes, P. carinii and P. murina. The P. jirovecii genome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential for myo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting that Pneumocystis species are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified in P. carinii and P. murina, while P. jirovecii contained only the ITR1 homolog. The ITR and inositol metabolism genes in P. murina and P. carinii were expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation of in vitro culture with inositol yielded significant improvement of the viability of P. carinii for days 7 through 14. IMPORTANCE Microbes in the genus Pneumocystis are obligate pathogenic fungi that reside in mammalian lungs and cause Pneumocystis pneumonia in hosts with weakened immune systems. These fungal infections are not responsive to standard antifungal therapy. A long-term in vitro culture system is not available for these fungi, impeding the study of their biology and genetics and new drug development. Given that all genomes of the Pneumocystis species analyzed lack the genes for inositol synthesis and contain inositol transporters, Pneumocystis fungi, like S. pombe, appear to be inositol auxotrophs. Inositol is important for the pathogenesis, virulence, and mating processes in Candida albicans and Cryptococcus neoformans, suggesting similar importance within the Pneumocystis species as well. This is the first report to (i) characterize genes in the inositol phosphate metabolism and transport pathways in Pneumocystis species and (ii) identify inositol as a supplement that improved the viability of P. carinii in in vitro culture.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2150-7511

URL الوصول: https://doaj.org/article/a90f0403ce65430d96f95420c972db6b

المؤلفون: Fabiano G. Nery, Jeffrey A. Welge, David Fleck, Wade Weber, L. Rodrigo Patino, Jeffrey R. Strawn, Caleb M. Adler, Stephen M. Strakowski, Melissa P. DelBello

المصدر: Journal of Affective Disorders. 331:238-244

مصطلحات موضوعية: Psychiatry and Mental health, Clinical Psychology

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::6f275d25cd9c252e9c510cb081928193
https://doi.org/10.1016/j.jad.2023.03.025

المؤلفون: Jhanvi N. Desai, Abigail Muccilli, Luis Tron Esqueda, Andrew Norman, Jeffrey A. Welge

المصدر: ASPET 2023 Annual Meeting Abstract - Central Nervous System Pharmacology - Behavioral.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::cbe1ee42f918a97feef8c382cb309d50
https://doi.org/10.1124/jpet.122.147450