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31.
Clement C. Zai Arun K. Tiwari Marina Mazzoco Vincenzo de Luca Daniel J. Müller Sajid A. Shaikh Falk W. Lohoff Natalie Freeman Aristotle N. Voineskos Steven G. Potkin Jeffrey A. Lieberman Herbert Y. Meltzer Gary Remington James L. Kennedy 《Journal of psychiatric research》2013
Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up to 25% of patients receiving long-term first-generation antipsychotic treatment. Its etiology is unclear, but family studies suggest that genetic factors play an important role in contributing to risk for TD. The vesicular monoamine transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD because it regulates the release of neurotransmitters implicated in TD, including dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug used in the treatment of hyperkinetic movement disorders, including TD. We examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that encodes VMAT2 for association with TD in our sample of chronic schizophrenia patients (n = 217). We found a number of SNPs to be nominally associated with TD occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the rs2015586 marker which was previously found associated with TD in the CATIE sample ( Tsai et al., 2010), as well as the rs363224 marker, with the low-expression AA genotype appearing to be protective against TD (p = 0.005). We further found the rs363224 marker to interact with the putative functional D2 receptor rs6277 (C957T) polymorphism (p = 0.001), supporting the dopamine hypothesis of TD. Pending further replication, VMAT2 may be considered a therapeutic target for the treatment and/or prevention of TD. 相似文献
32.
Lindsay N. Avolio Tyler J. S. Smith Ana Navas-Acien Kate Kruczynski Nora Pisanic Pranay R. Randad Barbara Detrick Rebecca C. Fry Alexander van Geen Walter Goessler Ruth A. Karron Sabra L. Klein Elizabeth L. Ogburn Marsha Wills-Karp Kelsey Alland Kaniz Ayesha Brian Dyer Md. Tanvir Islam Habibat A. Oguntade Md. Hafizur Rahman Hasmot Ali Rezwanul Haque Saijuddin Shaikh Kerry J. Schulze A. K. M. Muraduzzaman A. S. M. Alamgir Meerjady S. Flora Keith P. West Jr. Alain B. Labrique Christopher D. Heaney for the JiVitA Maternal Child Health Nutrition Research Project 《Paediatric and perinatal epidemiology》2023,37(2):165-178
Background
Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity.Objectives
The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy.Population
The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018–2019.Design
Prospective, longitudinal pregnancy and birth cohort.Methods
We conducted home visits to enrol pregnant women in the late first or early second trimester (11–17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants.Preliminary Results
We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 μg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) μg/L and 33.1 (19.6, 56.5) μg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median.Conclusions
The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. Registration : NCT03930017. 相似文献33.
Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach 下载免费PDF全文
Vaughn L. Culbertson Shaikh E. Rahman Grayson C. Bosen Matthew L. Caylor Megan M. Echevarria Dong Xu 《Pharmacotherapy》2018,38(9):888-898
Study Objective
Serotonergic adverse drug events (ADEs) are caused by enhanced intrasynaptic concentrations of 5‐hydroxytryptamine (5‐HT). No systematic process currently exists for evaluating cumulative 5‐HT and off‐target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5‐HT drugs in serotonin syndrome (SS) reports.Data Sources
Publicly available databases including the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), ChEMBL, DrugBank, PubChem, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were queried for computational and pharmacologic data.Design
An in‐house bioinformatics TargetSearch program ( http://dxulab.org/software ) was used to characterize 71 serotonergic drugs interacting at 13 serotonin receptor subtypes and serotonin reuptake transporter protein (SERT). In addition, off‐target interactions at norepinephrine transporter (NET), monoamine oxidase (MAO), and muscarinic receptors were included to define seven polypharmacological drug cohorts. Serotonin syndrome reports for each serotonergic drug were extracted from FAERS by using the Sternbach and Hunter criteria.Measurements and Main Results
A proportional reporting adverse drug reaction (ADR) ratio (PRR) was calculated from each drug's total ADEs and SS case reports and aggregated by drug bioactivity cohorts. Triple‐receptor interactions had a disproportionately higher number of SS cases using both the Hunter criteria (mean PRR 1.72, 95% CI 1.05–2.39) and Sternbach (mean PRR 1.54, 95% CI 1.29–1.79). 5‐Hydroxytryptamine agonists were associated with a significantly lower proportion of SS cases using the Hunter and Sternbach criteria, respectively (mean PRR 0.49, 95% CI 0.17–0.81 and mean PRR 0.49, 95% CI 0.15–0.83). Drugs with disproportionately higher participation in SS vary considerably between the two diagnostic criteria.Conclusion
The SEBM model suggests a possible polypharmacological role in SS. Although further research is needed, off‐target receptor activity may help explain differences in severity of toxicity and clinical presentation. 相似文献34.
Fawad Ur Rehman Tianyu Du Sana Shaikh Xuerui Jiang Yun Chen Xiaoqi Li Huan Yi Jiang Hui Baoan Chen Matthias Selke Xuemei Wang 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(8):2619-2631
Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl4, FeCl2), whereas Na2SeO3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al. 相似文献
35.
Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group 总被引:9,自引:0,他引:9
Stravitz RT Kramer AH Davern T Shaikh AO Caldwell SH Mehta RL Blei AT Fontana RJ McGuire BM Rossaro L Smith AD Lee WM;Acute Liver Failure Study Group 《Critical care medicine》2007,35(11):2498-2508
OBJECTIVE: To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers. METHODS: In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of > or =25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation. CONCLUSIONS: The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies. 相似文献
36.
Gary R. Schooler Juan C. Infante Michael Acord Adina Alazraki Govind B. Chavhan James Christopher Davis Geetika Khanna Ajaykumar C. Morani Cara E. Morin HaiThuy N. Nguyen Mitchell A. Rees Raja Shaikh Abhay Srinivasan Judy H. Squires Elizabeth Tang Paul G. Thacker Alexander J. Towbin 《Pediatric blood & cancer》2023,70(Z4):e29965
Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy. 相似文献
37.
38.
Abhisek Bhattarai Behdad Pouran Janne T. A. Mäkelä Rubina Shaikh Miitu K. M. Honkanen Mithilesh Prakash Heikki Kröger Mark W. Grinstaff Harrie Weinans Jukka S. Jurvelin Juha Töyräs 《Journal of orthopaedic research》2020,38(10):2230-2238
Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent. 相似文献
39.