1,015 research outputs found

    Hyaluronan Signaling during Ozone-Induced Lung Injury Requires TLR4, MyD88, and TIRAP

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    Ozone exposure is associated with exacerbation of reactive airways disease. We have previously reported that the damage-associated molecular pattern, hyaluronan, is required for the complete biological response to ambient ozone and that hyaluronan fragments signal through toll-like receptor 4 (TLR4). In this study, we further investigated the role of TLR4 adaptors in ozone–induced airway hyperresponsiveness (AHR) and the direct response to hyaluronan fragments (HA). Using a murine model of AHR, C57BL/6J, TLR4−/−, MyD88−/−, and TIRAP−/− mice were characterized for AHR after exposure to either ozone (1 ppm×3 h) or HA fragments. Animals were characterized for AHR with methacholine challenge, cellular inflammation, lung injury, and production of pro-inflammatory cytokines. Ozone-exposed C57BL/6J mice developed cellular inflammation, lung injury, pro-inflammatory cytokines, and AHR, while mice deficient in TLR4, MyD88 or TIRAP demonstrated both reduced AHR and reduced levels of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-6 and KC. The level of hyaluronan was increased after inhalation of ozone in each strain of mice. Direct challenge of mice to hyaluronan resulted in AHR in C57BL/6J mice, but not in TLR4−/−, MyD88−/−, or TIRAP−/− mice. HA-induced cytokine production in wild-type mice was significantly reduced in TLR4−/−, MyD88−/−, or TIRAP−/− mice. In conclusion, our findings support that ozone-induced airway hyperresponsiveness is dependent on the HA-TLR4-MyD88-TIRAP signaling pathway

    Symptomatic Subcapsular and Perinephric Hematoma Following Ureteroscopic Lithotripsy for Renal Calculi

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    Objective: Ureteroscopic lithotripsy (URSL) is believed to be associated with less risk of symptomatic renal hematoma than extracorporeal shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL). We sought to document the rate of and risk factors for this rare complication following URSL for renal calculi. Methods: With Institutional Review Board approval, we reviewed 1087 cases of URSL performed between July 2009 and October 2012 for four surgeons. We identified cases for renal calculi complicated by symptomatic ?hematoma? by searching electronic medical records of patients undergoing URSL with a web-based search tool and cross-referencing with a departmental quality improvement database for postoperative complications. Chi-squared tests were used to assess risk factors. Results: Among 877 renal units exposed to URSL for renal calculi, 4 were complicated by symptomatic subcapsular hematomas (SH) and 3 by symptomatic perinephric hematomas (PH), yielding a 0.5% and 0.3% rate for each complication, respectively. Pain was the primary presenting symptom. Almost all cases presented within 24 to 48 hours postop. Two PH patients required postoperative blood transfusion. Four patients (two SH, two PH) were hospitalized for observation. Ureteral sheaths were used in two cases (one PH and one SH). There was no association with age, diabetes, body mass index (BMI), or operative duration (p-values all>0.05). However, hematoma did correlate with female gender, preoperative hypertension, preoperative ureteral stenting, intraoperative ureteral sheath use, and postoperative ureteral stenting (all p-values<0.0001). Conclusions: While symptomatic hematoma is a complication of URSL, the rate of such outcome (0.8%) is far less than that reported by prior series with SWL and PCNL. This may partially be attributable to collection biases, where subclinical cases are not imaged, or anchoring biases, where clinicians attribute symptoms to another possible etiology. This outcome can be morbid, but can often be conservatively managed with observation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140379/1/end.2014.0176.pd

    Contemporary Practice Patterns of Flexible Ureteroscopy for Treating Renal Stones: Results of a Worldwide Survey

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    Introduction: Flexible ureteroscopy (fURS) is increasingly used in the treatment of renal stones. However, wide variations exist in technique, use, and indications. To better inform our knowledge about the contemporary state of fURS for treating renal stones, we conducted a survey of endourologists worldwide. Methods: An anonymous online questionnaire assessing fURS treatment of renal stones, consisting of 36 items, was sent to members of the Endourology Society in October 2014. Responses were collected through the SurveyMonkey system over a 3-month period. Results: Questionnaires were answered by 414 surgeons from 44 countries (response rate 20.7%). U.S. surgeons accounted for 34.4% of all respondents. fURS was routinely performed in 80.0% of institutions, with 40.0% of surgeons performing >100 cases/year. Respondents considered fURS to be first-line therapy for patients with renal stones 2?cm. Basket displacement for lower pole stones was routinely performed by 55.8%. Ureteral access sheaths (UAS) were preferred for every case by 58.3%. Respondents frequently utilized high-power lasers and dusting techniques. Criteria for determining stone-free rate were defined as zero fragments or residual fragment (RF) <1, <2, <3, and <4?mm by 30.9%, 8.9%, 31.5%, 15.8%, and 11.2% of respondents, respectively. Conclusion: The overwhelming majority of endourologists surveyed consider fURS as a first-line treatment modality for renal stones, especially those <2?cm. Use of UAS, high-power holmium lasers, and dusting technique has become popular among practitioners. When defining stone free after fURS, the majority of endourologists used a zero fragment or RF <2?mm definition.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140082/1/end.2015.0260.pd

    Transcriptomic analysis of field-droughted sorghum from seedling to maturity reveals biotic and metabolic responses.

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    Drought is the most important environmental stress limiting crop yields. The C4 cereal sorghum [Sorghum bicolor (L.) Moench] is a critical food, forage, and emerging bioenergy crop that is notably drought-tolerant. We conducted a large-scale field experiment, imposing preflowering and postflowering drought stress on 2 genotypes of sorghum across a tightly resolved time series, from plant emergence to postanthesis, resulting in a dataset of nearly 400 transcriptomes. We observed a fast and global transcriptomic response in leaf and root tissues with clear temporal patterns, including modulation of well-known drought pathways. We also identified genotypic differences in core photosynthesis and reactive oxygen species scavenging pathways, highlighting possible mechanisms of drought tolerance and of the delayed senescence, characteristic of the stay-green phenotype. Finally, we discovered a large-scale depletion in the expression of genes critical to arbuscular mycorrhizal (AM) symbiosis, with a corresponding drop in AM fungal mass in the plants' roots

    Prospectus, March 7, 1984

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    CONGRESS RETURNS TO A \u27MOST IMPORTANT\u27 STUDENT AID DEBATE; News Digest; Four paintings stolen from Parkland; \u27Job Training and Partnership Act\u27: JTPA \u27good opportunity for dedicated\u27; PC Happenings: TV programs for busy parents, Parkland announces registration, Polish folk arts at Parkland; Sargent talks to Lifelong Learners\u27 Club; Yaxley scholarship; Stu-Go News; \u27Planned Parenthood\u27--pro choice organization; In the Library--Paperbacks; Nolen enjoys differences; What is Sadie Hawkins Day?; Did You Know...; Scholarship news for real estate students; Tuexdo styles are changing; What did you thinnk of the Grammy Awards?; Classifieds; \u27Good looking coed\u27 hunt draws lots of photos; Urbana construction will increase; Learning to relax can kill stress; \u27Women\u27s History Week\u27 honored; Parkland Christian Fellowship to sponsor conference; Weather conditions force closing; Math contest at Parkland; Financia; aid for summer and fall; The latest in swimwear; \u27Western look\u27 changing; Creative Corner...Especially for you!!: Believe..., Creed, Dream, The End, Darkness...; All Up to Me, Listening to an old..., Father to Son, How to know just what is real..., For Larry, Hi, I\u27m crazy ...; Bite the Bullet, Answer, Why can\u27t we see?, Love sparked nu the heat of summer...,Keg, A low rumble starts..., Oh, Mothers..., Has the human race forgot to look at a sunset..., I tried to play your game..., You\u27ve let me down...; Jackson leads the way at this year\u27s Grammy awards; Dexter--valuable asset; $50,000 and silence \u27cheap way for MSU to avoid lawsuit\u27; In the Library--; Channel 12 fund drive stresses \u27TV worth paying for\u27; Woody Allen\u27s latest hilarious; \u27Foghat\u27 hits C/U March 18; Predictions for the upcoming Academy Awards; \u27Big Country\u27 to appear; \u27Full Metal Jacket\u27 talent search; \u27The Right Stuff\u27 finally opens in area; Energetic movie should do well; Baseball Schedule; Bank president--NFL referee; High School Notes; Softball Schedule; Cobra baseball to start; Women win tournament; Lake Land advances in sectional; Mens basketball scores; I.M. News; Cobra men advance to sectional; Cobras end up with last year\u27s record; Tae Kwon Do showed display; Cooper remembers 6 good years; First basketball coach tells how it was; NJCAA meethttps://spark.parkland.edu/prospectus_1984/1029/thumbnail.jp

    Towards a comprehensive research and development plan to support the control, elimination and eradication of neglected tropical diseases.

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    To maximise the likelihood of success, global health programmes need repeated, honest appraisal of their own weaknesses, with research undertaken to address any identified gaps. There is still much to be learned to optimise work against neglected tropical diseases. To facilitate that learning, a comprehensive research and development plan is required. Here, we discuss how such a plan might be developed

    Differential Regulation of the PGC Family of Genes in a Mouse Model of Staphylococcus aureus Sepsis

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    The PGC family of transcriptional co-activators (PGC-1α [Ppargc1a], PGC-1β [Ppargc1b], and PRC [Pprc]) coordinates the upregulation of mitochondrial biogenesis, and Ppargc1a is known to be activated in response to mitochondrial damage in sepsis. Therefore, we postulated that the PGC family is regulated by the innate immune system. We investigated whether mitochondrial biogenesis and PGC gene expression are disrupted in an established model of Staphylococcus aureus sepsis both in mice with impaired innate immune function (TLR2−/− and TLR4−/−) and in wild-type controls. We found an early up-regulation of Ppargc1a and Ppargc1b post-infection (at 6 h) in WT mice, but the expression of both genes was concordantly dysregulated in TLR2−/− mice (no increase at 6 h) and in TLR4−/− mice (amplified at 6 h). However, the third family member, PRC, was regulated differently, and its expression increased significantly at 24 h in all three mouse strains (WT, TLR2−/−, and TLR4−/−). In silico analyses showed that Ppargc1a and Ppargc1b share binding sites for microRNA mmu-mir-202-3p. Thus, miRNA-mediated post-transcriptional mRNA degradation could account for the failure to increase the expression of both genes in TLR2−/− mice. The expression of mmu-mir-202-3p was measured by real-time PCR and found to be significantly increased in TLR2−/− but not in WT or TLR4−/− mice. In addition, it was found that mir-202-3p functionally decreases Ppargc1a mRNA in vitro. Thus, both innate immune signaling through the TLRs and mir-202-3p-mediated mRNA degradation are implicated in the co-regulation of Ppargc1a and Ppargc1b during inflammation. Moreover, the identification of mir-202-3p as a potential factor for Ppargc1a and Ppargc1b repression in acute inflammation may open new avenues for mitochondrial research and, potentially, therapy
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