148 research outputs found
Pharmacovigilance Evaluation of the Association Between DPP-4 Inhibitors and Heart Failure: Stimulated Reporting and Moderation by Drug Interactions
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Gulf War Illness: Risk of Cognitive Decline and Dementia
No full textGulf War Illness: Risk of Cognitive Decline and Dementia 1Nidhi Patel, 1Fabian Mantilla, 2Mayur S. Parmar, PhD 1Class of 2026, Dr. Kiran C. Patel College of Osteopathic Medicine 2Assistant Professor, Pharmacology. Dr. Kiran C. Patel College of Osteopathic Medicine Objective. This review highlights the current understanding of neurological dysfunction associated with Gulf War Illness (GWI), specifically focusing on cognitive impairment and dementia as key complications. Background. GWI is a chronic multi-system disorder affecting a significant portion of veterans who served in the 1990-1991 Gulf War. Methods. This review synthesizes evidence from human and preclinical primary peer-reviewed studies evaluating the cognitive impairment in GWI patients and preclinical studies elucidating the impact of similar toxic chemical agents exposed to GWVs on cognitive impairment. Result. Cognitive impairment is a common feature of GWI and is prevalent in Gulf War veterans (GWVs). According to widely used diagnostic criteria, GWI is characterized by cognitive decline. Studies have shown atrophy and functional abnormalities in the brains of individuals with GWI. Inflammation has been indicated in the cognitive decline associated with GWI. Elevated inflammatory markers are linked to reduced hippocampal volume. Disruption of gene expression that could contribute to neurodegeneration and cognitive impairment has been noted with exposure to chemicals associated with the GWI. In veterans with GWI, high levels of tau autoantibodies have been detected in the peripheral blood, potentially indicating tau abnormalities, which are strongly connected to cognitive impairment. Conclusion. Cognitive impairment is one of the defining characteristics of GWI, and it will be essential to conduct routine cognitive assessments in GWI patients and GWVs to identify this neurologic impairment early in the patient. Grants. This study did not receive funding or grants
The Role of ERK5 in Dopamine Neuronal Survival
No full textThe extracellular signal-regulated kinases (ERKs) 1, 2, and 5 play important physiological roles in neurogenesis, neutrite outgrowth, and neuronal viability in the central nervous system. In this study, ERK1, 2, and 5 expression and activation were examined in the substantia nigra (SN), striatum (STR), and ventral tegmental area (VTA) during postnatal development and normal aging using western blot analysis. An age-related decrease in phosphorylated/activated ERK5 (p-ERK5) was observed in the SN and STR, whereas an increase in total ERK1 was observed in all three regions. Higher expression of total and phosphorylated ERK5 was observed at postnatal day zero (PND0) in all dopaminergic regions, which declined with the postnatal development. However, expression of total ERK1 and ERK2 increased with the postnatal development. An increase in the p-ERK1 and p-ERK2 peak was observed in both dopaminergic cell bodies containing regions, SN and VTA at PND7 as compared to PND0. In contrast, no such peak was observed in the STR with the postnatal development.
In primary DA cultures of the SN and VTA, inhibition of ERK5 but not ERK1 and ERK 2 activation significantly decreased DA neuronal viability. Pretreatment with the glial cell line-derived neurotrophic factor (GDNF) or dopamine neuron stimulating peptide-11 (DNSP-11) did not protect human dopaminergic SH-SY5Y cells against 6-hydroxydopamine (6-OHDA)-induced toxicity at 24 h. However, GDNF or DNSP-11 pretreatment protected against 6-OHDA-induced increase in apoptotic signaling, as measured by caspase-3/7 activity at 6 h; indicating that GDNF and DNSP-11 blocks some, but not all, of the cytotoxic effects of 6-OHDA. Treatment of SH-SY5Y cells with GDNF or DNSP-11 resulted in activation of ERK1, 2, and 5 signaling. Infusion of DNSP-11 into the STR also resulted in modulation of ERK1, 2, and 5 signaling. Increase in tyrosine hydroxylase expression was observed in the STR (42%) and SN (32%), at 7 days and 6 h, respectively, after DNSP-11 infusion.
Together, these data suggest the essential role of ERK1, 2, and 5 kinases in dopamine neuronal survival, especially ERK5. These data raise the possibility that a decline ERK5 signaling may play a role in age-related impairments in dopaminergic function
Deterministic annealing algorithm: tutorial, application to pickup and delivery problem and computational aspects
No full textThe deterministic annealing (DA) method, used for the solution of several nonconvex problems, offers the ability to avoid shallow local minima of a given cost surface and the ability to minimize the cost function even when there are many local minima. The method is established in a probabilistic framework through basic information-theoretic techniques such as maximum entropy and random coding. It arises naturally in the context of statistical mechanics by the emulation of a physical process whereby a solid is slowly cooled and at zero temperature assumes its minimum energy configuration. We start with the introduction to DA method and then present a tutorial to describe the algorithm steps. Also, we discuss the connections of DA method with Statistical Mechanics and Rate-Distortion Theory. Next, we present the application of DA method to pickup and deliver scheduling problem with time windows. Finally, a computational complexity analysis for DA is presented for a given temperature schedule. The case study focuses on the geometric cooling law , where is the temperature at time .Submission published under a 24 month embargo labeled 'U of I only', the embargo will last until 2017-05-01The student, Pratik Mayur Parekh, accepted the attached license on 2015-04-29 at 11:47.The student, Pratik Mayur Parekh, submitted this Thesis for approval on 2015-04-29 at 11:54.This Thesis was approved for publication on 2015-04-30 at 15:06.DSpace SAF Submission Ingestion Package generated from Vireo submission #8183 on 2015-07-22 at 14:19:02Made available in DSpace on 2015-07-22T22:34:01Z (GMT). No. of bitstreams: 2
PAREKH-THESIS-2015.pdf: 1206816 bytes, checksum: 55dda3d59a2fd68c519e62a706ce7365 (MD5)
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Previous issue date: 2015-04-30Embargo set by: Seth Robbins for item 79929
Lift date: 2017-07-22T22:34:16Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 79929 on 2017-07-23T09:15:19Z
Dicarboxylic Acid
No full textDicarboxylic acids are organic compounds that contain two functional carboxylic acid (–COOH) groups. Industrially, they are important in production of polyester, polyols, polyamides, and nylon and as a precursor to active pharmaceutical ingredients and additives. Dicarboxylic acids are important water-soluble components of atmospheric aerosols. Succinic, adipic, and glutaric acid may be harmful if inhaled, swallowed, or absorbed through skin. All these acids alone or in combination do not show any mutagenic effect. Some of the dicarboxylic acids (sebacic acid) have been advocated to have anti-hyperglycemic effect, whereas analysis of serum free fatty acids from patients with Reye\u27s syndrome (acute encephalopathy with visceral steatosis syndrome) had revealed the presence of dicarboxylic acids in over half of the patients\u27 total free fatty acids; both medium-chain (6–12 carbon lengths) and long-chain (14–18 carbon lengths) dicarboxylic acids were identified in such studies. Malathion, a well-known organophosphate pesticide, was previously marketed as Malathion dicarboxylic acid, is fetotoxic and toxic to infants and children.https://nsuworks.nova.edu/hpd_facbooks/1000/thumbnail.jp
Methylglyoxal
No full textMethylglyoxal (MG) is a reactive α-dicarbonyl, and may be the most important reactive aldehyde that is primarily generated endogenously in cells and exogenously due to autoxidation process. Interestingly, diabetes was the first disease in which evidence emerged for the increased formation of MG in the body. MG is also a major precursor of advanced glycation end products. It has the ability to enhance protein glycation, oxidative stress, or inflammation, in addition to exerting a toxic effect on insulin secretion from pancreatic β-cells. It is a toxic by-product of glycolysis and many other metabolic pathways. It has been suggested that MG culminates in cytotoxic effects via reactive oxygen and reactive nitrogen species. In mammalian cells, this reactive metabolite is detoxified via the glutathione-dependent glyoxalase pathway forming d-lactate, involving lactoylglutathione lyase (GLO1; EC 4.4.1.5) and hydroxyacylglutathione hydrolase (GLO2; EC 3.2.1.6). Methylglyoxal has been identified as the dominant antibacterial constituent of manuka honey. MG is used in organic synthesis, as a flavoring agent, and in tanning leather. Exposure routes include endogenous formation in the body, ingestion, and inhalation.https://nsuworks.nova.edu/hpd_facbooks/1001/thumbnail.jp
Telomerase-associated apoptotic events by mushroom Ganoderma lucidum on premalignant human urothelial cells
No full textAuthor name used in this publication: Mayur Danny I. Gohel2007-2008 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishedGreen (AAM
At the Heart of Care: An Exploration of Family and Professional Perspectives in Paediatric Cardiology
No full textPaediatric cardiology presents a complex and emotionally charged landscape for families and professionals alike. For those affected by congenital heart diseases such as hypoplastic left heart syndrome (HLHS), the journey often begins before birth, involving difficult decisions and a lifelong trajectory of care. Families frequently face ongoing psychological and practical challenges, while healthcare professionals must navigate how best to support them. This thesis explores experiences from both perspectives: families of children with HLHS and healthcare professionals working in paediatric cardiology. It aims to understand the psychosocial impacts involved and assess the feasibility of integrating psychologically informed approaches (PIA) to support more holistic care.Section one systematically reviews the literature investigating the family experiences of supporting a child with HLHS. Twelve studies were selected and thematically synthesised, leading to the generation of four overarching themes exploring key psychosocial elements of navigating this condition: toll on the parents, worries about the child, observed differences to parenting, and experiences of support. Bronfenbrenner’s ecological systems theory could provide context to explaining family distress and emphasise the difficulties experienced and importance of effective support.Section two aims to investigate healthcare professionals’ perspective on the feasibility of integrating psychologically informed approaches (PIA) into paediatric cardiology, given the several psychosocial challenges involved with caring for and treating this clinical population. Four themes were generated using a template analysis: perceptions of PIA, systemic and organisational considerations, navigating interprofessional dynamics and perceived responsibilities, and skills and behaviour development. Successful integration of this framework may come from context-sensitive strategies that support individuals and organisations to address current barriers to improve holistic care of children and young people with a cardiac condition.</p
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