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111.
112.
Richard S.P. Huang James Haberberger Kimberly McGregor Douglas A. Mata Brennan Decker Matthew C. Hiemenz Mirna Lechpammer Natalie Danziger Kelsie Schiavone James Creeden Ryon P. Graf Roy Strowd Glenn J. Lesser Evangelia D. Razis Rupert Bartsch Athina Giannoudis Talvinder Bhogal Nancy U. Lin Lajos Pusztai Jeffrey S. Ross Carlo Palmieri Shakti H. Ramkissoon 《The oncologist》2021,26(10):835-844
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Andge Valiakhmetova Sergey Gorelyshev Alexander Konovalov Yuri Trunin Alexander Savateev David E. Kram Eric Severson Amanda Hemmerich Claire Edgerly Daniel Duncan Nicholas Britt Richard S.P. Huang Julia Elvin Vincent Miller Jeffrey S. Ross Laurie Gay Joshua McCorkle Andrew Rankin Rachel L. Erlich Yakov Chudnovsky Shakti H. Ramkissoon 《The oncologist》2020,25(2):e198-e202
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Manisha Holmes Zia Flaminio Mridula Vardhan Fangxi Xu Xin Li Orrin Devinsky Deepak Saxena 《Epilepsia》2020,61(12):2619-2628
One-third of epilepsy patients have drug-resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut-brain-axis are likely to shed light on epilepsy pathogenesis, anti-seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood-brain barrier disruption, and altered neuromodulators. High-throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug-sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low-carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted. 相似文献
115.
Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome
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Dani VS Chang Q Maffei A Turrigiano GG Jaenisch R Nelson SB 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(35):12560-12565
Rett Syndrome (RTT) is a devastating neurological disorder that is caused by mutations in the MECP2 gene. Mecp2-mutant mice have been used as a model system to study the disease mechanism. Our previous work has suggested that MeCP2 malfunction in neurons is the primary cause of RTT in the mouse. However, the neurophysiological consequences of MeCP2 malfunction remain obscure. Using whole-cell patch-clamp recordings in cortical slices, we show that spontaneous activity of pyramidal neurons is reduced in Mecp2-mutant mice. This decrease is not caused by a change in the intrinsic properties of the recorded neurons. Instead, the balance between cortical excitation and inhibition is shifted to favor inhibition over excitation. Moreover, analysis of the miniature excitatory postsynaptic currents (mEPSCs)/inhibitory postsynaptic currents (mIPSCs) in the Mecp2-mutant cortex reveals a reduction in mEPSC amplitudes, without significant change in the average mIPSC amplitude or frequency. These findings provide the first detailed electrophysiological analysis of Mecp2-mutant mice and provide a framework for understanding the pathophysiology of the disease and tools for studying the underlying disease mechanisms. 相似文献
116.
Defect in the lymphoid compartment might account for CD8+-mediated effects in the pathophysiology of pure red cell aplasia 总被引:1,自引:0,他引:1
Rameshwar P Ramkissoon SH Sundararajan S Gascón P 《Clinical immunology (Orlando, Fla.)》2003,108(3):248-256
Pure red cell aplasia (PRCA) is a rare hematological syndrome characterized by the lack of red cell progenitors in an otherwise normocellular bone marrow. Many agents and mechanisms have been implicated in the pathophysiology of PRCA, including immune-mediated dysfunctions. This report describes three patients with PRCA with unknown underlying cause and showed that for each, increases in CD8+ cells blunted the maturation of early erythroid (BFU-E). Each patient subsequently responded to immunosuppressive therapy. Peripheral blood mononuclear cells from age- and sex-matched healthy controls showed comparable distribution of CD3, CD4 and CD16, but significant increase in CD8 and decreased CD19. The distribution of lymphocyte subsets correlated with mitogen responses, but showed no difference in allogeneic responses when compared to controls. The adherent population in PRCA is important for mediating the hyper-immune state of patients, when IL-2 levels were used as readout. There was a trend for decreased BFU-E in patients, but marked reduction for late erythroid progenitors (CFU-E). CD8+ cells from PRCA blunted the maturation of BFU-E, despite increasing erythropoietin concentrations. These results strongly suggest that there are defects in the lymphoid compartment that feedback on the erythroid lineage of PRCA. 相似文献
117.
The fine morphology of glomeruli present in the mesonephroi of mouse embryos from days 12 to 14 of gestational age is described. The glomeruli are rudimentary, ephemeral structures which probably result from temporary juxtaposition of a blood capillary to the ventral extremity of a mesonephric tubule. Yet, they might possess a certain degree of functionality. 相似文献
118.
119.
Anil Babanrao Gangwe Deepshikha Agrawal Aashish Kumar Gangrade Swapnil Madhukar Parchand Deepanshu Agrawal Raj Vardhan Azad 《Indian journal of ophthalmology》2021,69(8):2171
Purpose:The aim of this study was to report the treatment outcomes of early and deferred laser in infants of aggressive posterior retinopathy of prematurity (APROP) after initial treatment with intravitreal Ranibizumab (IVR).Methods:In a prospective, randomized, interventional study, infants with APROP received IVR (0.25 mg) and were randomized into two groups prior to laser. Laser was done at 1 week (group 1) or at 6 weeks or earlier if there was a recurrence of plus disease (group 2). The structural outcome, number of laser spots, duration of laser procedure and refractive error at 6 months were compared. Favorable structural outcome was defined as, complete regression of disease at 6 weeks after laser.Results:63 eyes of 32 infants with APROP were enrolled. Mean gestational age (GA) and birth weight (BW) were 30.2 ± 2.3 weeks and 1294 ± 372.8 grams respectively. GA, BW, and disease severity were comparable at baseline. 27 (90%) eyes in group 1 and 29 (93.5%) eyes in group 2 had favorable structural outcome (P = 0.61) at 6 weeks after laser. Eyes in group 2 (2149.8 ± 688.7) required lesser number of laser spots than group 1 (2570.8 ± 615) (P = 0.01). At six months, more eyes in group 1 had myopic refractive error (Mean spherical equivalent: –1.0D ± 1.3) than those in group 2 (Mean spherical equivalent: 0.5D ± 1.9) (P = 0.002).Conclusion:Infants with APROP receiving IVR have comparable structural outcomes after an early or deferred laser. Moreover, eyes undergoing deferred laser require less number of laser spots and have a less myopia at 6 months after laser. 相似文献
120.
We describe enhanced mydriasis in maximally medically dilated pupils during indirect diode laser therapy for threshold retinopathy of prematurity in 20 consecutive eyes of 10 neonates. 相似文献