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Isolation, structural analysis, and expression characteristics of the maize nuclear factor Y gene families NUCLEAR FACTOR-Y (NF-Y) has been shown to play an important role in growth, development, and response to environmental stress. A NF-Y complex, which consists of three subunits, NF-YA, NF-YB, and, NF-YC, binds to CCAAT sequences in a promoter to control the expression of target genes. Although NF-Y proteins have been reported in Arabidopsis and rice, a comprehensive and systematic analysis of ZmNF-Y genes has not yet been performed. To examine the functions of ZmNF-Y genes in this family, we isolated and characterized 50 ZmNF-Y (14 ZmNF-YA, 18 ZmNF-YB, and 18 ZmNF-YC) genes in an analysis of the maize genome. The 50 ZmNF-Y genes were distributed on all 10 maize chromosomes, and 12 paralogs were identified. Multiple alignments showed that maize ZmNF-Y family proteins had conserved regions and relatively variable N-terminal or C-terminal domains. The comparative syntenic map illustrated 40 paralogous NF-Y gene pairs among the 10 maize chromosomes. Microarray data showed that the ZmNF-Y genes had tissue-specific expression patterns in various maize developmental stages and in response to biotic and abiotic stresses. The results suggested that ZmNF-YB2, 4, 8, 10, 13, and 16 and ZmNF-YC6, 8, and 15 were induced, while ZmNF-YA1, 3, 4, 6, 7, 10, 12, and 13, ZmNF-YB15, and ZmNF-YC3 and 9 were suppressed by drought stress. ZmNF-YA3, ZmNF-YA8 and ZmNF-YA12 were upregulated after infection by the three pathogens, while ZmNF-YA1 and ZmNF-YB2 were suppressed. These results indicate that the ZmNF-Ys may have significant roles in the response to abiotic and biotic stresses.
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How do different delivery schedules of tailored web-based physical activity advice for breast cancer survivors influence intervention use and efficacy? The purpose of the study is to investigate the impact of differing delivery schedules of computer-tailored physical activity modules on engagement and physical activity behaviour change in a web-based intervention targeting breast cancer survivors. Insufficiently active breast cancer survivors (n = 492) were randomly assigned to receive one of the following intervention schedules over 12 weeks: a three- module intervention delivered monthly, a three-module intervention delivered weekly or a single module intervention. Engagement with the website (number of logins, time on site, modules viewed, action plans completed) was measured using tracking software. Other outcomes (website acceptability, physical activity behaviour) were assessed using online surveys. Physical activity outcomes were analysed using regression models for both study completers and when applying intention-to-treat (using multiple imputation). Completers allocated to the monthly module group rated the intervention higher (b = 2.2 95 % CI = 0.02-4.53) on acceptability and had higher levels of resistance-training (IRR = 1.88, 95 % CI = 1.16-3.04) than those in the single module group. When accounting for missing data, these differences were no longer significant. The completion of at least two action plans was higher among those allocated to the monthly module group compared to those in the weekly module group (53 vs 40 %, p = 0.02); though the completion of at least two modules was higher in the weekly module group compared to the monthly module group (60 vs 46 %; p = 0.01). There were no other significant between group differences observed. This study provides preliminary evidence that web-based computer-tailored interventions can be used to increase physical activity among breast cancer survivors. Further, there were some outcome differences based on how the tailored modules were delivered, with the most favourable outcomes observed in the monthly delivery group. This study will be useful for informing the design of future web-based interventions targeting breast cancer survivors.
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Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities. A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary's Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor. The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UC s, respectively. Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.
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[ "Vision", "Guides", "Selection", "of", "Freeze", "or", "Flight", "Defense", "Strategies", "in", "Mice", "In", "prey", "species", "such", "as", "mice", ",", "avoidance", "of", "predators", "is", "key", "to", "survival", "and", "drives", "instinctual", "behaviors", "like", "freeze", "or", "flight", "[", "1", ",", "2", "]", ".", "Sensory", "signals", "guide", "the", "selection", "of", "appropriate", "behavior", "[", "3", "]", ",", "and", "for", "aerial", "predators", "only", "vision", "provides", "useful", "information", ".", "Surprisingly", ",", "there", "is", "no", "evidence", "that", "vision", "can", "guide", "the", "selection", "of", "escape", "strategies", ".", "Fleeing", "behavior", "can", "be", "readily", "triggered", "by", "a", "rapidly", "looming", "overhead", "stimulus", "[", "4", "]", ".", "Freezing", "behavior", ",", "however", ",", "has", "previously", "been", "induced", "by", "real", "predators", "or", "their", "odors", "[", "5", "]", ".", "Here", ",", "we", "discover", "that", "a", "small", "moving", "disk", ",", "simulating", "the", "sweep", "of", "a", "predator", "cruising", "overhead", ",", "is", "sufficient", "to", "induce", "freezing", "response", "in", "mice", ".", "Looming", "and", "sweeping", "therefore", "provide", "visual", "triggers", "for", "opposing", "flight", "and", "freeze", "behaviors", "and", "provide", "evidence", "that", "mice", "innately", "make", "behavioral", "choices", "based", "on", "vision" ]
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Vision Guides Selection of Freeze or Flight Defense Strategies in Mice In prey species such as mice, avoidance of predators is key to survival and drives instinctual behaviors like freeze or flight [1, 2]. Sensory signals guide the selection of appropriate behavior [3], and for aerial predators only vision provides useful information. Surprisingly, there is no evidence that vision can guide the selection of escape strategies. Fleeing behavior can be readily triggered by a rapidly looming overhead stimulus [4]. Freezing behavior, however, has previously been induced by real predators or their odors [5]. Here, we discover that a small moving disk, simulating the sweep of a predator cruising overhead, is sufficient to induce freezing response in mice. Looming and sweeping therefore provide visual triggers for opposing flight and freeze behaviors and provide evidence that mice innately make behavioral choices based on vision alone.
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Short-term effects of a vibrotactile neck -based treatment device for positional obstructive sleep apnea: preliminary data on tolerability and efficacy Positional supine obstructive sleep apnea syndrome (OSAS) characterizes a subgroup of patients suffering from OSAS. Several devices designed to limit supine position have been developed, but evidences of their efficacy and safety are lacking. It is unclear whether a neck-worn vibrating device could induce positional change in patients with positional OSAS. We evaluated the efficacy of a neck -worn device to induce supine avoidance positional feedback over a short-term trial in OSAS patients and its impact on sleep quality and polysomnographyc indexes. Twenty patients with positional apneas / hypopneas were prospectively studied. Baseline characteristics of daytime somnolence and risk of sleep apnea were screened and the efficacy of a 3-day trial of supine - avoidance therapy by vibrotactile neck worn device assessed by reporting the self-perceived change in quality of sleep and performing cardio-respiratory polysomnography. Comparison between baseline and treatment results was performed. The neck device produced a reduction in overall apnea-hypopnea index (AHI) (mean AHI pre =16.8/h and post =4.4/h, P<0.0001), oxygen desaturation (pre =13.7/h and post =3.8/h, P<0.0001) and Respiratory Disturbance Indexes (RDI) (20.0/h vs. 5.2/h; P<0.0001).The time spent in supine position decreased from 62.1% to 33.7% of the total (P<0.001). However, the impact on the perceived quality of sleep was unpredictable. The neck position therapy device is effective in restricting supine sleep, improving AHI and related polysomnographic indexes. However, at least in a short-term trial, it seems unable to improve the patient's sleep quality.
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Operative surgical nuances of modified extradural temporopolar approach with mini-peeling of dura propria based on cadaveric anatomical study of lateral cavernous structures Extradural temporopolar approach (ETA) has been modified as less invasive manner and named as trans-superior orbital fissure (SOF) approach with mini-peeling technique. The present study discusses the operative nuances of this modified technique on the basis of cadaveric study of lateral cavernous structures. In five consecutive cadaveric specimens, we performed an extradural anterior clinoidectomy with mini-peeling of the dura propria to expose the anterior clinoid process entirely. We also investigated the histological characteristics of the lateral cavernous sinus (CS) between the dura propria and periosteal dura at the SOF, foramen rotundum (FR), and foramen ovale (FO) levels, and of each trigeminal nerve division. Coronal histological examination of the lateral wall of the CS showed invagination of the dura propria and periosteal dura into the SOF. In contrast, no such invagination was observed at the levels of the FR and FO. This finding supports the technical rationale of the only skeletonization of the SOF for peeling of the dura propria but not FR. In addition, our modified ETA method needs only minimal dural incision between the SOF and FR where no cranial nerves are present. Our technical modification of ETA may be recommended for surgical treatment of paraclinoid lesions to reduce the risk of intraoperative neurovascular injury.
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Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by orthopaedic surgeons because of their possible influence on bone-healing. This belief stems from multiple studies, in particular animal studies, that show delayed bone-healing or nonunions associated with NSAID exposure. The purpose of this review was to critically analyze the quality of published literature that evaluates the impact of NSAIDs on clinical bone-healing. A MEDLINE and Embase search was conducted to identify all articles relating to bone and fracture-healing and the utilization of NSAIDs. All human studies, including review articles, were identified for further analysis. Non-English-language manuscripts and in vitro and animal studies were excluded. A total of twelve clinical articles and twenty-four literature reviews were selected for analysis. The quality of the clinical studies was assessed with a modified Coleman Methodology Score with emphasis on the NSAID utilization. Review articles were analyzed with regard to variability in the cited literature and final conclusions. The mean modified Coleman Methodology Score (and standard deviation) was significantly lower (p = 0.032) in clinical studies that demonstrated a negative effect of NSAIDs on bone-healing (40.0 ± 14.3 points) compared with those that concluded that NSAIDs were safe (58.8 ± 10.3 points). Review articles also demonstrated substantial variability in the number of cited clinical studies and overall conclusions. There were only two meta-analyses and twenty-two narrative reviews. The mean number (and standard deviation) of clinical studies cited was significantly greater (p = 0.008) for reviews that concluded that NSAIDs were safe (8.0 ± 4.8) compared with those that recommended avoiding them (2.1 ± 2.1). Unanimously, all reviews admitted to the need for prospective randomized controlled trials to help clarify the effects of NSAIDs on bone-healing. This systematic literature review highlights the great variability in the interpretation of the literature addressing the impact of NSAIDs on bone-healing. Unfortunately, there is no consensus regarding the safety of NSAIDs following orthopaedic procedures, and future studies should aim for appropriate methodological designs to help to clarify existing discrepancies to improve the quality of care for orthopaedic patients. This systematic review highlights the limitations in the current understanding of the effects of NSAIDs on bone healing. Thus, withholding these medications does not have any proven scientific benefit to patients and may even cause harm by increasing narcotic requirements in cases in which they could be beneficial for pain management. This review should encourage further basic-science and clinical studies to clarify the risks and benefits of anti-inflammatory medications in the postoperative period, with the aim of improving patient outcomes.
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Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over- expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis. Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically, RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that XIST could simultaneously interact with EZH2 to suppress transcription of its potential target KLF2. Additionally, rescue experiments revealed that XIST 's oncogenic functions were partly depending on silencing KLF2 expression. Collectively, our findings expound how XIST over- expression endows an oncogenic function in NSCLC.
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Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages Macrophages play a crucial role in the progression of osteoarthritis (OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The aim of this study was to evaluate the direct effects of macrophage subtypes on cartilage by culturing macrophage conditioned medium (MCM) on human articular cartilage. Human OA cartilage explants were cultured with MCM of pro-inflammatory M (IFNγ + TNFα), or anti-inflammatory M (IL-4) or M (IL-10) human monocyte-derived macrophages. To assess effects of anti-inflammatory macrophages, the cartilage was cultured with a combination of MCM phenotypes as well as pre-stimulated with IFNγ + TNFα cartilage before culture with MCM. The reactions of the explants were assessed by gene expression, nitric oxide (NO) production and release of glycosaminoglycans (GAGs). M (IFNγ + TNFα) MCM affected OA cartilage by upregulation of IL1B (Interleukin 1β), IL6, MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5), while inhibiting ACAN (aggrecan) and COL2A1 (collagen type II). M (IL-10) upregulated IL1B and Suppressor of cytokine signaling 1 (SOCS1). NO production and GAG release by the cartilage was increased when cultured with M (IFNγ + TNFα) MCM. M (IL-4) and M (IL-10) did not inhibit the effects of M (IFNγ + TNFα) MCM of neither phenotype affected IFNγ + TNFα pre-stimulated cartilage, in which an inflammatory gene response was deliberately induced. M (IFNγ + TNFα) macrophages have a prominent direct effect on OA cartilage, while M (IL-4) and M (IL-10) do not inhibit the effects of M (IFNγ + TNFα), or IFN γ+ TNFα induced inflammation of the cartilage. Therapies aiming at inhibiting cartilage degeneration may take this into account by directing suppression of pro-inflammatory macrophages or stimulation of anti-inflammatory macrophages.
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In vivo assessment of periodontal structures and measurement of gingival sulcus with Optical Coherence Tomography: a pilot study There has been increasing interest on the development of clinically acceptable, more sensitive and specific methods for non-invasive diagnosis in Periodontics. In this pilot study, the performance of an Optical Coherence Tomography (OCT) system in imaging periodontal structures in humans was evaluated. Gingival sulcus depth measurements were obtained and compared with traditional probes. In total, 445 sites of 23 periodontally healthy individuals were measured by 3 instruments: North Carolina manual probe, Florida automated probe and OCT at 1325 nm. To obtain quantitative measurements from OCT images, the gingival refractive index was also determined. Discomfort / pain perception and the duration of examinations were compared among the instruments. The analysis of OCT images allowed the identification of relevant anatomic dental and periodontal regions. The average sulcus depth measured by OCT, 0.85 ± 0.27 mm and 0.87 ± 0.28 mm, was lower than the values obtained by manual and automated probing. Discomfort / pain were prevalent for traditional probes, which are invasive methods, than for the non-invasive OCT technique. OCT has the potential to be a reliable tool for in vivo periodontal tissues evaluation and for reproducible sulcus depth measurements in healthy sites. Further technological advances are required to reduce the procedure time and promote evaluation of posterior oral regions. Photonic assessment of periodontal tissue with OCT (top) in a clinical environment, showing tooth / gingiva features (bottom).
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De novo assembly of the blunt snout bream (Megalobrama amblycephala) gill transcriptome to identify ammonia exposure associated microRNAs and their targets De novo transcriptome sequencing is a robust method for microRNA (miRNA) target gene prediction, especially for organisms without reference genomes. Following exposure of Megalobrama amblycephala to ammonia (0.1 or 20 mg L(-1)), two cDNA libraries were constructed from the fish gills and sequenced using Illumina HiSeq 2000. Over 90 million reads were generated and de novo assembled into 46, 615 unigenes, which were then extensively annotated by comparing to different protein databases, followed by biochemical pathway prediction. The expression of 2666 unigenes significantly differed; 1961 were up-regulated, while 975 were down-regulated. Among these, 250 unigenes were identified as the targets for 10 conserved and 4 putative novel miRNA families by miRNA target computational prediction. We examined expression of ssa-miRNA-21 and its target genes by real-time quantitative PCR and found agreement with the sequencing data. This study demonstrates the feasibility of identifying miRNA targets by transcriptome analysis. The transcriptome assembly data represent a substantial increase in the genomic resources available for Megalobrama amblycephala and will be useful for gene expression profile analysis and miRNA functional annotation.
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Near-Infrared Polymeric Nanoparticles with High Content of Cyanine for Bimodal Imaging and Photothermal Therapy The discovery and synthesis of theranostic nanomedicines with high loading of imaging and therapeutic agents is challenging. In this work, a polymer assembling strategy was used to make nanoparticles with exceptionally high loading of theranostic agent. As an example, poly(heptamethine) was synthesized via multicomponent Passerini reaction, and then assembled into nanoparticles in the presence of poly(ethylene glycol)2k-block-poly(d,l-lactide)2k (PEG-PLA) with high heptamethine loading (>50%). The formed nanoparticles could be used for bimodal bioimaging and photothermal therapy. The bimodal bioimaging provided complementary message about biodistribution, and photothermal treatment inhibited the growth of cervical carcinoma upon laser irradiation. This assembly of polymers formed by imaging and therapeutic agents opens new possibilities for the construction of multifunctional nanomedicines.
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Limited effectiveness of patent blue dye in addition to isotope scanning for identification of sentinel lymph nodes: Cross-sectional real-life study in 1024 breast cancer patients Although morbidity is reduced when sentinel lymph node (SLN) biopsy is performed with dual isotopic and blue dye identification, the effectiveness of adding blue dye to radioisotope remains debated because side effects including anaphylactic reactions. Using data from a prospectively maintained database, 1884 lymph node-negative breast cancer patients who underwent partial mastectomy with SLN mapping by a dual-tracer using patent blue dye (PBD) and radioisotope were retrospectively studied between January 2000 and July 2013. Patients with tumors <3 cm and with >1 node detected by one of the two techniques (N = 1024) were included in this real-life cross-sectional study. Among the 1024 patients, 274 had positive SLN detected by isotopic and/or PBD staining. Only 4 patients having no detectable radioactivity in the axilla had SLN identified only by PBD staining (blue-only) while 26 patients had SLN only identified by isotopic detection (hot-only) illustrating failure rates of 9.5% (26/274) and 1.5% (4/274), respectively. Among these four patients, two had negative lymphoscintigraphy. Therefore, the contribution of PBD to metastatic nodes identification was relevant for only 2/274 patients (0.8%). Three patients (0.3%) had an allergic reaction with PBD, and anaphylactic shock occurred in two cases (0.2%). The added-value of PBD to reduce the false-negative rate of SLN mapping is only limited to the rare cases in which no radioactivity is detectable in the axilla (<1%). When a radioisotope mapping agent is available, the use of PBD should be avoided, because it can induce anaphylaxis.
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Snack intake is reduced using an implicit, high-level construal cue Priming a high level construal has been shown to enhance self-control and reduce preference for indulgent food. Subtle visual cues have been shown to enhance the effects of a priming procedure. The current study therefore examined the combined impact of construal level and a visual cue reminder on the consumption of energy-dense snack s. A student and community-based adult sample with a wide age and body mass index (BMI) range (N = 176) were randomly assigned to a high or low construal condition in which a novel symbol was embedded. Afterward participants completed a taste test of ad libitum snack foods in the presence or absence of the symbol. The high (vs. the low) construal level prime successfully generated more abstract responses (p < .0001) and reduced intake when the cue - reminder was present (p = .02) but not when it was absent (p = .40). Priming high construal level thinking reduces consumption of high energy dense snacks in the presence of a visual cue - reminder. This may be a practical technique for reducing overeating and has the potential to be extended to other unhealthy behaviors. (PsycINFO Database Record
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A comparison of the extent and pattern of cognitive impairment among predialysis, dialysis and transplant patients: a cross sectional study from Australia A comparison of the extent and pattern of cognitive impairment among predialysis, dialysis and transplant patients: a cross sectional study from Australia AIM: The aim of this study was to compare the extent of cogntive impairment and the types of cognitive deficits in an Australian cohort of four patient groups with end stage kidney disease. Characteristics predicting the presence of cognitive impairment were also evaluated. Observational cross sectional study of one hundred and fifty five patients with end stage kidney disease recruited from a regional Australian renal unit. Eligible participants included those whose estimated Glomerular Filtration Rate was < 30 ml/min/1.73 m(2); were undertaking peritoneal or hemodialysis, or had received a kidney transplant. The Montreal Cognitive Assessment tool was used to screen the study participants for cognitive impairment and evaluate cognitive deficits. Cognitive impairment was defined as a total Montreal Cognitive Assessment tool score ≤24/30. The extent of cognitive impairment varied between the four groups with end stage kidney disease. Factors predicting the presence of cognitive impairment included undertaking dialysis, age ≥65, male gender, and the presence of diabetes or cerebrovascular disease. Deficits in executive function, attention, language, visuospatial skills, memory and orientation were common amongst the study participants, and these deficits varied according to which end stage kidney disease group the participants were in. Limitations to the study included the cross sectional design and that the presence of confounders like depression were not recorded. The impact of disparities in the cognitive capabilities identified in this study are likely to be far reaching. Tailoring of education and self management programs to the cognitive deficits of individuals is required.
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Metagenomic recovery of phage genomes of uncultured freshwater actinobacteria Low - GC Actinobacteria are among the most abundant and widespread microbes in freshwaters and have largely resisted all cultivation efforts. Consequently, their phages have remained totally unknown. In this work, we have used deep metagenomic sequencing to assemble eight complete genomes of the first tailed phages that infect freshwater Actinobacteria. Their genomes encode the actinobacterial - specific transcription factor whiB, frequently found in mycobacteriophages and also in phages infecting marine pelagic Actinobacteria. Its presence suggests a common and widespread strategy of modulation of host transcriptional machinery upon infection via this transcriptional switch. We present evidence that some whiB - carrying phages infect the acI lineage of Actinobacteria. At least one of them encodes the ADP-ribosylating component of the widespread bacterial AB toxins family (for example, clostridial toxin). We posit that the presence of this toxin reflects a 'trojan horse' strategy, providing protection at the population level to the abundant host microbes against eukaryotic predators.
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Pupil dynamics with periodic flashes: effect of age on mesopic adaptation The purpose of this study is to determine the pupillary dynamics with periodical flashes from a peripheral glare source, in similar conditions to night driving, while focusing on dependence with age. We measured two groups of people: youth and adults. Maximum pupil size decreases due to periodic flashes. Latency does not present significant differences. The reduction of pupil size is greater for older adults. The presence of a peripheral and periodic glare source modifies the pupil size. This leads to a reduction of retinal illuminance, which is greater for older adults.
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Adequacy of initial evaluation of fever in long-term care facilities Febrile residents in long-term care facilities (LTCF) might be inadequately evaluated by caregivers. The present study aimed to examine the factors associated with inadequacy of initial fever evaluations by caregivers at night in LTCF. We carried out a cross-sectional study among a convenience sample of caregivers employed at 11 LTCF in Japan using a vignette-based questionnaire. The respondents were randomly assigned to one of two scenarios describing a mild or severe febrile episode in an LTCF resident at night. The respondents ' thinking patterns were classified based on influential factors in their fever evaluation. Associations between adequacy of evaluation and respondents ' characteristics were evaluated using generalized linear mixed models. A total of 34% of fever evaluations among caregivers were considered to be inadequate regarding the necessity for examination by a physician, due in most cases to underestimating the severity of the fever. Respondents ' thinking patterns in fever evaluation were significantly associated with the adequacy of the evaluation. Caregivers who placed particular importance on the preferences of residents and families versus other factors including the resident 's febrile condition, were more likely to make an inadequate evaluation than those who did not. Our findings here suggest that eagerness to comply with residents ' preference in fever evaluation could prompt caregivers not to call for an appropriate diagnostic procedure. Geriatr Gerontol Int 2016; ••: ••-••.
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Climate change increases the risk of herbicide - resistant weeds due to enhanced detoxification Global warming will increase the incidence of metabolism -based reduced herbicide efficacy on weeds and, therefore, the risk for evolution of non-target site herbicide resistance. Climate changes affect food security both directly and indirectly. Weeds are the major biotic factor limiting crop production worldwide, and herbicides are the most cost-effective way for weed management. Processes associated with climatic changes, such as elevated temperatures, can strongly affect weed control efficiency. Responses of several grass weed populations to herbicides that inhibit acetyl-CoA carboxylase (ACCase) were examined under different temperature regimes. We characterized the mechanism of temperature -dependent sensitivity and the kinetics of pinoxaden detoxification. The products of pinoxaden detoxification were quantified. Decreased sensitivity to ACCase inhibitors was observed under elevated temperatures. Pre-treatment with the cytochrome-P450 inhibitor malathion supports a non-target site metabolism -based mechanism of herbicide resistance. The first 48 h after herbicide application were crucial for pinoxaden detoxification. The levels of the inactive glucose-conjugated pinoxaden product (M5) were found significantly higher under high- than low- temperature regime. Under high temperature, a rapid elevation in the level of the intermediate metabolite (M4) was found only in pinoxaden - resistant plants. Our results highlight the quantitative nature of non-target -site resistance. To the best of our knowledge, this is the first experimental evidence for temperature -dependent herbicide sensitivity based on metabolic detoxification. These findings suggest an increased risk for the evolution of herbicide - resistant weeds under predicted climatic conditions.
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2201 ], [ 2202, 2204 ] ]
Integration of Serum Protein Biomarker and Tumor Associated Autoantibody Expression Data Increases the Ability of a Blood-Based Proteomic Assay to Identify Breast Cancer Despite significant advances in breast imaging, the ability to accurately detect Breast Cancer (BC) remains a challenge. With the discovery of key biomarkers and protein signatures for BC, proteomic technologies are currently poised to serve as an ideal diagnostic adjunct to imaging. Research studies have shown that breast tumors are associated with systemic changes in levels of both serum protein biomarkers (SPB) and tumor associated autoantibodies (TAAb). However, the independent contribution of SPB and TAAb expression data for identifying BC relative to a combinatorial SPB and TAAb approach has not been fully investigated. This study evaluates these contributions using a retrospective cohort of pre - biopsy serum samples with known clinical outcomes collected from a single site, thus minimizing potential site-to-site variation and enabling direct assessment of SPB and TAAb contributions to identify BC. All serum samples (n = 210) were collected prior to biopsy. These specimens were obtained from 18 participants with no evidence of breast disease (ND), 92 participants diagnosed with Benign Breast Disease (BBD) and 100 participants diagnosed with BC, including DCIS. All BBD and BC diagnoses were based on pathology results from biopsy. Statistical models were developed to differentiate BC from non-BC (i.e., BBD and ND) using expression data from SPB alone, TAAb alone, and a combination of SPB and TAAb. When SPB data was independently used for modeling, clinical sensitivity and specificity for detection of BC were 74.7% and 77.0%, respectively. When TAAb data was independently used, clinical sensitivity and specificity for detection of BC were 72.2% and 70.8%, respectively. When modeling integrated data from both SPB and TAAb, the clinical sensitivity and specificity for detection of BC improved to 81.0% and 78.8%, respectively. These data demonstrate the benefit of the integration of SPB and TAAb data and strongly support the further development of combinatorial proteomic approaches for detecting BC.
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Nursing care through the perception of hospitalized children to describe the perception of hospitalized children of school age, on nursing care and understand what are, from their perspective, the best ways to address it to when performing such care. qualitative, descriptive, exploratory research, with concepts of Vygotsky used as theoretical framework. The data collection occurred through interviews mediated by drawings and was performed with ten school children, with the interview later transcribed and submitted to a thematic analysis. showed the importance of playing during hospitalization, of a friendly and caring approach and providing explanations regarding the performed procedures. nursing professionals need to consider how the children would like to receive the care being provided, so that their singularities are respected, characterizing nursing actions according to a perspective of the whole human being.
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A Systematic Review on Infliximab and Adalimumab Drug Monitoring: Levels, Clinical Outcomes and Assays Immunogenicity to therapeutic proteins has been linked to loss of response by a large percentage of patients taking anti-tumor necrosis factor-alpha agents. Drug monitoring can be extremely useful, allowing physicians to adjust the therapeutic scheme individually. This article aims to systematically review the published data with respect to cutoff levels of infliximab (IFX) and adalimumab (ADA) and relate them to the methodology adopted for quantification of IFX and ADA levels and clinical outcomes. The PubMed database was searched to identify studies focusing on the association between IFX or ADA cutoff levels and clinical outcomes in patients with inflammatory bowel disease. Of the 1654 articles initially selected by queries, 20 were included. A receiver operating characteristic curve analysis was performed to identify cutoff levels of IFX or ADA that correlated with a clinical outcome, but only 6 studies performed the same analysis for antidrug antibody levels. Cutoff levels were different between studies. The methodology chosen for level quantifications, clinical outcomes, and sample size and characteristics were also different. Nevertheless, measurement of drug levels should be performed during maintenance, and with loss of response, with persistent high levels of C-reactive protein, and when mucosal lesions are still present. In these scenarios, drug and antidrug levels were correlated with clinical outcomes. Concerning drug levels monitoring any methodology is adequate. With respect to antidrug antibody levels, it will be necessary to define a gold standard method or to establish different cutoff levels for different methodologies.
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Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2'Z,3'E)-6-Bromoindirubin-3'-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI.
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Prevalence of otologic signs and symptoms in adult patients with temporomandibular disorders: a systematic review and meta-analysis This study aims to estimate the prevalence of otologic signs and symptoms in adult patients with temporomandibular disorders (TMD). Search strategies were developed for each of the following databases: PubMed, LILACS, Scopus, Web of Science, Proquest, LIVIVO, and Google Scholar and OpenGrey was used to assess the grey literatur e. It was included in this review only observational studies using either research diagnostic criteria (RDC)/ TMD or DC / TMD indexes were selected. The Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute was used to assess the risk of bias of the included studies. A proportion random effects meta-analysis was conducted within the eight included studies. Eight studies met the eligibility criteria and were selected. All of the included studies used the RDC / TMD and report associated otologic signs and symptoms. The studies were clustered into groups based on prevalence for each individual sign or symptom. The most prevalent otologic symptom associated with TMD was ear fullness (74.8 % standard deviation (SD), 43.02 to 96.25 %; n = 50), followed by otalgia (55.1 % SD, 31.78 to 77.30; n = 386), tinnitus (52.1 % SD, 38.43 to 65.74; n = 1293), vertigo (40.8 % SD, 11.29 to 74.72; n = 374), and hearing loss (38.9 % SD, 2.83 to 85.46; n = 744). The prevalence of otologic signs and symptoms in adult patients with TMD is high. The most prevalent otologic symptom in patient adults with TMD is ear fullness. This study intends to provide understanding over the prevalence of otologic signs and symptoms in TMD cases in adults.
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Amyloid Aggregates Arise from Amino Acid Condensations under Prebiotic Conditions Current theories on the origin of life reveal significant gaps in our understanding of the mechanisms that allowed simple chemical precursors to coalesce into the complex polymers that are needed to sustain life. The volcanic gas carbonyl sulfide (COS) is known to catalyze the condensation of amino acids under aqueous conditions, but the reported di-, tri-, and tetra-peptides are too short to support a regular tertiary structure. Here, we demonstrate that alanine and valine, two of the proteinogenic amino acids believed to have been among the most abundant on a prebiotic earth, can polymerize into peptides and subsequently assemble into ordered amyloid fibers comprising a cross-β-sheet quaternary structure following COS - activated continuous polymerization of as little as 1 mm amino acid. Furthermore, this spontaneous assembly is not limited to pure amino acids, since mixtures of glycine, alanine, aspartate, and valine yield similar structures.
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The effects of gait time and trunk acceleration ratio during stair climbing in old-old adult females [Purpose] This study investigated the effects of gait time and trunk acceleration ratio in old-old adult females during stair climbing. [Subjects and Methods] Twenty-five older adult females who were able to walk independently volunteered for this study and were categorized into two age groups (older adults or old-old adults). Gait time and trunk acceleration ratio were measured using an accelerometer during stair climbing. [Results] Gait time and trunk acceleration ratio when climbing stairs were significantly higher in the old-old age group than in the older adults group. [Conclusions] These findings suggest that old-old females have decreased upper trunk control. In addition, gait time and the trunk acceleration ratio during stair climbing are useful clinical markers for predicting function and balance control ability in old-old elderly populations.
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Can mean platelet volume be used as a biomarker for asthma? Platelets play important roles in airway inflammation and are activated in inflammatory lung diseases, including asthma. We evaluated the mean platelet volume (MPV), used as a marker of platelet activation, in asthmatic patients during asymptomatic periods and exacerbations compared to healthy controls to determine whether MPV can be used as an indicator of inflammation. Our patient group consisted of 95 children with exacerbation of asthma who were admitted to our allergy clinic. The control group consisted of 100 healthy children matched for age, gender, and ethnicity. Mean platelet volume values of the patient group obtained during exacerbation of asthma were compared to those of the same group during the asymptomatic period and with the control group. We investigated factors that can affect the MPV values of asthma patients, including infection, atopy, immunotherapy treatment, and severity of asthma exacerbation. The patient group consisted of 50 (52.6%) boys and 45 (47.4%) girls with a mean age of 125 ±38 months old. Mean MPV values in the exacerbation period, the healthy period, and in the control group were 8.1 ±0.8 fl, 8.1 ±1.06 fl, and 8.2 ±0.9 fl, respectively; there were no significant differences between groups (p > 0.05). The severity of asthma, severity of asthma exacerbation, immunotherapy, coinfection, eosinophil count, and IgE level also had no effect on MPV (p > 0.05). Although platelets play a role in the pathophysiology of asthma, MPV measurement is insufficient to detect inflammation through platelets.
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Interoception and Positive Symptoms in Schizophrenia The present study focuses on the multifaceted concept of self-disturbance in schizophrenia, adding knowledge about a not yet investigated aspect, which is the interoceptive accuracy. Starting from the assumption that interoceptive accuracy requires an intact sense of self, which otherwise was proved to be altered in schizophrenia, the aim of the present study was to explore interoceptive accuracy in a group of schizophrenia patients, compared to healthy controls. Furthermore, the possible association between interoceptive accuracy and patients ' positive and negative symptomatology was assessed. To pursue these goals, a group of 23 schizophrenia patients and a group of 23 healthy controls performed a heartbeat perception task. Patients ' symptomatology was assessed by means of the Positive and Negative Syndrome Scale (PANSS). Results demonstrated significantly lower interoceptive accuracy in schizophrenia patients compared to healthy controls. This difference was not accounted for participants ' age, BMI, anxiety levels, and heart rate. Furthermore, patients ' illness severity, attention and pharmacological treatment did not influence their interoceptive accuracy levels. Interestingly, a strong positive relation between interoceptive accuracy and positive symptoms severity, especially Grandiosity, was found. The present results demonstrate for the first time that interoceptive accuracy is altered in schizophrenia. Furthermore, they prove a specific association between interoceptive accuracy and positive symptomatology, suggesting that the symptom Grandiosity might be protective against an altered basic sense of self in patients characterized by higher sensibility to their inner bodily sensations.
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Holistic Patterns as an Instrument for Predicting the Performance of Promising Young Soccer Players - A 3-Years Longitudinal Study Multidimensional and dynamic talent models represent the current state of the art, but these demands have hardly ever been implemented so far. One reason for this could be the methodological problems associated with these requirements. This paper will present a proposal for dealing with this, namely for examining the development of young soccer players holistically. The patterns formed by the constructs net hope, motor abilities, technical skills and biological maturity were examined, as well as the way in which these holistic pattern s are related to subsequent sporting success. 119 young elite soccer players were questioned and tested three times at intervals of 1 year, beginning at the age of 12. At the age of 15, the level of performance reached by the players was determined. At all three measuring points, four patterns were identified, which displayed partial structural and high individual stability. The highly skilled players, scoring above average on all factors - but not necessarily those having the highest overall scores - were significantly more likely to advance to the highest level of performance. Failure - fearing fit players, i.e., physically strong, early developed players but with some technical weaknesses, have good chances of reaching the middle performance level. In contrast, none of the achievement - oriented, highly skilled, late - matured or late-matured, low skilled players reached the highest performance level. The results indicate the importance of holistic approaches for predicting performance among promising soccer talents in the medium-term and thus provide valuable clues for their selection and promotion.
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miR‑221 targets HMGA2 to inhibit bleomycin ‑induced pulmonary fibrosis by regulating TGF‑β1 / Smad3 -induced EMT MicroRNA (miR)-221 plays an essential role in the epithelial-mesenchymal transition (EMT). High mobility group AT-hook 2 (HMGA2), is a key regulator of EMT. However, the role of miR‑221 in pulmonary fibrosis, and the association between miR‑221 and HMGA2 remain largely unknown. For this purpose, we examined the expression of miR‑221 and HMGA2 in human idiopathic pulmonary fibrosis (IPF) tissues and pulmonary cells, namely the adenocarcinoma A549 and human bronchial epithelium (HBE) cell lines, and found that the expression of miR‑221 was inhibited in both tissues and cells whereas high mRNA and protein expression of HMGA2 was observed. Additionally, transforming growth factor‑β1 (TGF‑β1) induced the EMT, characterized by the upregulated expression of the mesenchymal markers, namely N‑cadherin, vimentin, α‑smooth muscle actin, collagen I and collagen III, and the downregulated expression of the epithelial marker E-cadherin in A549 and HBE cells. We then performed transfection with miR‑221 mimics, and found that the expression of phosphorylated - Smad3 in miR‑221 ‑ overexpressing cells was significantly downregulated, compared with that in the TGF‑β1 -treated cells without transfection. Furthermore, the overexpression of miR‑221 decreased the expression of HMGA2, suppressed the EMT, and inhibited the proliferation of A549 and HBE cells. HMGA2 was directly targeted by miR‑221 which was confirmed by the dual-luciferase reporter gene assay. Finally, a mouse model of bleomycin (BLM)‑induced pulmonary fibrosis was used to confirm the effect of miR‑221 on EMT. Hematoxylin and eosin staining showed that BLM induced thicker alveolar walls and more collagen deposition, whereas miR‑221 treatment reduced lung fibrosis and the tissues exhibited thinner alveolar walls and normal lung alveoli. Furthermore, the EMT process was suppressed following miR‑221 injection. Taken together, these findings sugest that miR‑221 targets HMGA2 to inhibit BLM ‑induced pulmonary fibrosis through the TGF‑β1 / Smad3 signaling pathway.
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Isolation and characterization of lignocellulose nanofibers from different wheat straw pulps Wheat straw was cooked under different pulping processes: Soda (100°C, 7% NaOH, 150min), Kraft (170°C, 16% alkalinity, 25% sulfidity, 40min) and Organosolv (210°C, 60% ethanol, 60min). Once the pulps were obtained, lignocellulose nanofibers (LCNF) were isolated by mechanical process and TEMPO -mediated oxidation followed by a high pressure homogenization. After pulping process, the different pulps were characterized and its chemical composition was determined. The pulps characterization indicates that the Soda process is the process that, despite producing less delignification, retains much of the hemicelluloses in the pulp, being this content a key factor in the nanofibrillation process. Regarding the LCNF obtained by mechanical process, those nanofibers isolated from Organosolv wheat pulp (OWP) and Kraft wheat pulp (KWP) show low values for nanofibrillation yield, specific surface area and greater diameter. However, those nanofibers isolated from Soda wheat pulp (SWP) reach much higher values for these parameters and presents a diameter of 14nm, smaller than those obtained by TEMPO -mediated oxidation from OWP. Smaller diameters are generally obtained in TEMPO - oxidized LCNF. This work concludes that the lignin content does not affect greatly to obtain LCNF as does the hemicellulose content, so it is accurate to use a soft pulping process.
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Association of testosterone and BDNF serum levels with craving during alcohol withdrawal Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol -dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results.
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Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury Spinal cord injury (SCI) is one of the most common and severe complications in spine injury. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. Proteasome beta-4 subunit (PSMB4) is the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo, and our previous study showed that PSMB4 is significantly associated with neuronal apoptosis in neuroinflammation. However, PSMB4 function in the necroptosis after SCI is unkown. RIP3, a key regulatory factor of necroptosis, correlates with the induction of necroptosis in various types of cells and signaling pathway. Upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PSMB4 during the pathological process of SCI. We found PSMB4 expression was significantly up-regulated 3 days after injury by western blot and immunohistochemical staining. Double immunofluorescent staining indicated obvious changes of PSMB4 expression occurred in neurons. Significant up-regulation of PSMB4 expression was observed in Rip3 positive neurons at 3 days after SCI, which indicated that PSMB4 might play a vital role in the regulation of Rip3. Overexpress and knockdown PSMB4 could intervene the RIP3 and Mixed lineage kinase domain-like protein (MLKL) pathway in Tumor necrosis factor-α (TNF-α) induced necroptosis cell model. Based on our experimental data, we boldly conclude that PSMB4 is associated with RIP3 involved necroptosis after SCI.
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Renoprotective Effect of Plantago Major Against Nephrotoxicity and Oxidative Stress Induced by Cisplatin The aim of this study was to investigate the possible renoprotective effect of Plantago major extract against cisplatin -induced nephrotoxicity in rats. Rats were divided into 6 groups. The first group was the control, group 2 was treated with cisplatin (7 mg/kg, single dose), and groups 3 to 6 received cisplatin with vitamin E (100 mg/kg) and Plantago major extract at doses of 300 mg/kg, 600 mg/kg, and 1200 mg/kg, for 20 days. On day12, serum concentration of urea, creatinine, and potassium significantly increased and sodium concentration significantly decreased in the cisplatin group compared with the control rats. However, serum creatinine, urea, and potassium concentrations were significantly lower in all of the Plantago major groups compared to the cisplatin group. Also, there was a significant elevation in serum sodium concentration in the Plantago major 600 mg/kg group compared to the cisplatin group on day12. Injection of cisplatin caused a significant elevation in malondialdehyde concentration but a significant decrease in catalase activity and total thiol content compared to the control group. Plantago major extract at 1200 mg/kg significantly improved malondialdehyde concentration and total thiol content compared to the cisplatin group. Catalase activity with Plantago major significantly increased at all doses compared to the cisplatin group. The current study suggests that Plantago major extract and vitamin E are able to improve kidney function as well as oxidative stress in cisplatin -induced renal toxicity in the rat.
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Argininosuccinic Acid Lyase Deficiency Missed by Newborn Screen Argininosuccinic acid lyase (ASL) deficiency, caused by mutations in the ASL gene (OMIM: 608310) is a urea cycle disorder that has pleiotropic presentations. On the mild end, ASL deficiency can manifest as nonspecific neurocognitive abnormalities without readily identifiable signs to differentiate it from other causes of intellectual disability or learning disabilities. Dietary management and arginine supplementation, if initiated early, may ameliorate symptoms .Because of the nonspecific nature of the symptoms and the possibility for therapeutic management, ASL deficiency is part of the recommended uniform screening panel for newborn screening in the USA. We report here a case of ASL deficiency that was missed on newborn screening in the USA .The case reported here has two known pathogenic mutations - one with no residual activity and one with reported 10% residual activity. Review of this newborn screening results showed subtle elevation of citrulline, overlapping the normal range. These findings suggest that newborn screening may be missing other patients with ASL deficiency with at least one hypomorphic allele. This case was diagnosed incidentally, but in retrospect had symptoms best attributed in full or in part to his ASA deficiency, including protein aversion, developmental delay, and seizures. This case highlights the importance of considering ASL deficiency in patients with nonspecific abnormal neurocognitive signs, such as epilepsy and developmental delay, even when newborn screening was normal.
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A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia. Final results of the GIMEMA LAL 0904 study In the GIMEMA LAL 0904 protocol, adult Ph+ acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post - remission phase together with chemotherapy. Due to the toxicity of this combined approach, the protocol was further amended to a sequential scheme based on imatinib plus steroids as induction, followed by consolidation with chemotherapy plus imatinib and, when applicable, by a hematopoietic stem cell transplant. Fifty-one patients (median age: 45.9 years) were enrolled in the final sequential protocol, hereby reported. At the end of induction (day +50), 96% of evaluable patients (n=49) achieved a complete hematologic remission; after consolidation, all were in complete hematologic remission. No deaths in induction were recorded. Overall survival and disease-free survival at 60 months are 48.8% and 45.8%, respectively. At day +50 (end of the imatinib induction), a log - reduction of BCR-ABL1 levels >1.3 was associated with a significantly more prolonged disease-free survival (55.6%, C.I. 95%: 39.0-79.3 vs 20%, C.I. 95%: 5.8-69.1; p =0.03), overall survival (59.1%, C.I. 95%: 42.3-82.6 vs 20%, C.I. 95%: 5.8-69.1, p =0.02) and lower relapse incidence (20.5%, C.I. 95%: 7.2-38.6 vs 60.0%, C.I. 95%: 21.6-84.3, p =0.01). Mean BCR-ABL1 levels remained significantly higher in patients who subsequently relapsed. Finally, BCR-ABL1p190 patients showed a significantly faster molecular response than BCR-ABL1p210 patients (p =0.023). Thought the study was not powered to evaluate the role of allogeneic stem cell transplant, allografting positively impacted on overall survival and disease-free survival. A sequential approach with imatinib alone in induction, consolidated by chemotherapy plus imatinib followed by a stem cell transplant is a feasible, well-tolerated and effective strategy for adult Ph+ acute lymphoblastic leukemia, leading to the best long-term survival rates so far reported. Trial ID: NCT00458848.
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Anatomic variations of levator scapulae in a normal cohort: an MRI study Accessory attachments of the levator scapulae (LS) muscle have been described in the literature in previous cadaveric studies, but there is little knowledge about the incidence and distribution. Knowledge of LS accessory attachments is relevant to clinicians working in the fields of radiology, surgery, neurology, and musculoskeletal medicine. The purpose of this study was to explore the incidence and spectrum of LS caudal accessory attachments in vivo using magnetic resonance (MR) imaging in a young cohort. MR images of the cervical spine were obtained from 37 subjects (13 males and 24 females) aged 18-36 years using an axial T1-weighted spin echo sequence acquired from a 3-Tesla MR scanner. The LS muscle was identified, and the presence of caudal accessory attachments was recorded and described. LS caudal accessory attachments were identified in 16 subjects (4 right, 6 left, and 6 bilateral; 12 female). Ten had unilateral accessory attachments to the serratus anterior, serratus posterior superior or the first/second rib. Four had bilateral accessory attachments to serratus anterior. One had bilateral accessory attachments to serratus posterior superior and unilateral accessory attachment to serratus anterior. One had bilateral attachments to both muscles. Both unilateral and bilateral LS caudal accessory attachments were present in nearly half of the subjects examined. They were relatively more frequent in females than males. The findings indicate that these accessory attachments are common, and in some cases, those accessory attachments can occur bilaterally and to more than one site.
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Progestin suppressed inflammation and cell viability of tumor necrosis factor-α -stimulated endometriotic stromal cells Endometriosis is an estrogen - dependent inflammatory disease. Progestins are a first-line treatment for endometriosis via activation of pituitary progesterone receptors and suppression of systemic estrogen: a less than optimal treatment. Increasing evidence is beginning to show that progestins may also influence local endometriotic cells, which may contribute to their clinical efficacy. Endometrial stromal cells (ESC) isolated from women with endometriosis were cultured with TNF-α to simulate an inflammatory environment. ESC were treated with the progestins, medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), or dienogest (DNG) and cytokine mRNA production, protein secretion, and cell viability measured. DNG, NETA, and MPA suppressed the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 from ESC. DNG and NETA only reduced the TNF-α -stimulated mRNA production. All three progestins suppressed TNF-α -stimulated ESC proliferation. Progestins may influence endometriotic stromal cells altering the inflammatory microenvironment and their clinical efficacy.
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Gut Microbiota and Alcoholic Liver Disease The gut-liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic / toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine. Several recent evidences from the literature show how gut microbiota composition can be altered by alcohol, affects IP and can be modulated by several nonpharmacological and pharmacological agents, becoming the target for ALD treatment. In this review we describe the definition of ALD, gut microbiota composition in healthy and ALD, definition and role of IP in ALD physiopathology and emerging evidences on gut microbiota modulation in ALD treatment from preliminary clinical and non-clinical studies.
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Chitosan grafted monomethyl fumaric acid as a potential food preservative The present study aims at in vitro antibacterial and antioxidant activity evaluation of chitosan modified with monomethyl fumaric acid (MFA) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as mediator. Three different kinds of chitosan derivatives Ch-Ds-1, Ch-Ds-2 and Ch-Ds-3 were synthesized by feeding different concentration of MFA. The chemical structures of resulting materials were characterized by (1)H NMR, (13)C NMR, HR-XRD, FT-IR and TNBS assay. The results showed that Ch-Ds-1, Ch-Ds-2 and Ch-Ds-3 were successfully synthesized. The % amino groups of chitosan modified by MFA were evaluated by TNBS assay and ranging from 1.82±0.05% to 7.88±0.04%. All the chitosan derivatives are readily soluble in water and swelled by dimethyl sulfoxide (DMSO), toluene and dimethyl formamide (DMF). The antioxidant activity for all the chitosan derivatives have been significantly improved (P<0.05) compared to the chitosan. Upon antibacterial activity at pH 4.0, all the chitosan derivatives showed significant (P<0.05) antibacterial activity against Gram positive Staphylococcus aureus, Listeria monocytogenes strains and Gram negative Escherichia coli and Salmonella enteritidis strains compared to chitosan. In conclusion, MFA modified chitosan has shown enhanced activities along with solubility, and could be used as a novel food preservative and packaging material for long time food safety and security.
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Transarterial chemoembolization of hepatocellular carcinoma with segmental portal vein tumour thrombus To evaluate the clinical outcome and safety of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with segmental or subsegmental portal vein tumour thrombus (sPVTT) in patients with preserved hepatic function, and to address the efficacy of additional chemoinfusion after TACE (TACE + CI). From January 2003 to December 2012, TACE was conducted on 81 patients with Child-Pugh score ≤7 who had HCC with sPVTT. Thirty-one of them underwent TACE + CI. The overall survival (OS) and serious adverse events (SAEs) were evaluated. The efficacy of TACE + CI was appraised after adjustment with inverse probability of treatment weighting (IPTW). The OS after TACE (median, 15.5 months) was significantly related with aspartate aminotransferase (hazard ratio [HR], 1.011), modified Barcelona Clinic Liver Cancer (BCLC) stage D (HR, 2.841), extrahepatic spread (HR, 4.862), and TACE + CI (HR, .367). The SAE incidence was significantly associated with modified BCLC stages (HR, 10.174 [proper-C] and 24.000 [D]). After IPTW adjustment, TACE + CI significantly improved OS (p = .028; HR, .511), but the SAE incidence was not significantly altered (p = .737; HR, .819). TACE can be an effective and safe treatment option for HCC with sPVTT in patients with preserved hepatic function. Furthermore, additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety. • TACE is effective and safe for treating HCC with sPVTT. • Modified BCLC stages can stratify the risk and benefit of TACE. • Additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety.
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Improved adipose tissue function with initiation of protease inhibitor - only ART Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART - naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI - only ART on SAT function in ART - naive subjects. In the HIVNAT-019 study, 48 HIV-infected, ART - naive Thai adults commencing PI - only ART comprising lopinavir / ritonavir / saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition. In a molecular substudy, 20 subjects underwent SAT biopsies at weeks 0, 2 and 24 for transcriptional, protein, mitochondrial DNA (mtDNA) and histological analyses. ClinicalTrials.gov registration number: NCT00400738. Over 24 weeks, limb fat increased (+416.4 g, P = 0.023), coinciding with larger adipocytes as indicated by decreased adipocyte density in biopsies (-32.3 cells /mm(2), P = 0.047) and increased mRNA expression of adipogenesis regulator PPARG at week 2 (+58.1%, P = 0.003). Increases in mtDNA over 24 weeks (+600 copies/cell, P = 0.041), decreased NRF1 mRNA expression at week 2 (-33.7%, P < 0.001) and increased COX2 / COX4 protein ratio at week 24 (+288%, P = 0.038) indicated improved mitochondrial function. Despite decreased AKT2 mRNA at week 2 (-28.6%, P = 0.002) and increased PTPN1 mRNA at week 24 (+50.3%, P = 0.016) suggesting insulin resistance, clinical insulin sensitivity [by homeostasis model assessment (HOMA-IR)] was unchanged. Initiation of PI - only ART showed little evidence of SAT toxicity, the changes observed being consistent with a return to health rather than contributing to lipodystrophy. icle
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Ambient PM2.5 Exposure and Mortality Due to Lung Cancer and Cardiopulmonary Diseases in Polish Cities Air pollution, one of ten most important causes of premature mortality worldwide, remains a major issue also in the EU, with more than 400,000 premature deaths due to exposure to PM2.5 reported yearly. The issue is particularly significant in Poland, where there is the highest concentration of PM2.5 among the UE countries. This study focused on the proportion of mortality due to lung cancer and cardiopulmonary diseases attributable to PM2.5 in eleven biggest Polish cities in the years 2006-2011. The findings demonstrate that the mean annual concentration of PM2.5 varied from 14.3 to 52.5 μg/m(3). The average population attributable fractions varied from 0.195 to 0.413 in case of lung cancer and from 0.130 to 0.291 for cardiopulmonary diseases. Such substantial values of this ratio translate into a considerable number of deaths, which ranged between 9.6 and 22.8 cases for lung cancer and 48.6 to 136.6 cases for cardiopulmonary diseases per 100,000 inhabitants. We conclude that the impact of PM2.5 concentration on the incidence of premature deaths is unduly high in Polish cities.
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" Predictors of provider - initiated HIV testing and counseling refusal by outpatient department clients in Wolaita zone, Southern Ethiopia: a case control study " "Despite different strategies designed to rapidly identify HIV infected individuals, majority of HIV -infected people are unaware of their sero-status in developing countries. The objective of this study was to assess predictors of provider -initiated HIV testing and counseling (PITC) refusal by outpatient department (OPD) clients in Wolaita zone, Southern Ethiopia. Facility based unmatched case control study was conducted on outpatient department clients in randomly selected seven health facilities in Wolaita zone, Southern Ethiopia in February 2012. A total of 291 participants (97 cases and 194 controls) were included in our study. Cases were patients who refused HIV test while controls were patients who tested for HIV after provider -initiated HIV testing and counseling (PITC) recommendation by outpatient department (OPD) clinicians. We used both quantitative and qualitative methods of data collection. Pretested interviewer administered questionnaires were used to collect quantitative data by trained nurses, and in-depth interview with 14 OPD clinicians was conducted by principal investigator to supplement quantitative findings. Bivariate and multivariate analyses were done to identify independent predictors of provider -initiated HIV testing and counseling refusal by OPD clients. Study participants who had stigmatizing attitude [AOR =6.09, (95 % CI: 1.70, 21.76)], who had perceived risk for HIV infection [AOR =5.23, (95 % CI: 2.22, 12.32)], who did not perceive the benefits of provider -initiated HIV testing and counseling [AOR =4.64, (95 % CI: 1.79, 12.01)], who did not get minimum recommended pretest information from their providers [AOR =2.98, (95 % CI: 1.06, 8.35)], who ever not heard of provider -initiated HIV testing and counseling service [AOR =2.41, (95 % CI: 1.14, 5.09)], and who were from urban area [AOR =2.40, (95 % CI =1.26, 4.57)] were more likely to refuse provider -initiated HIV testing and counseling service than their counterparts. Knowledge on HIV /AIDS, attitude towards people living with HIV /AIDS and perceived risk for HIV infection by clients were the major barriers for provider -initiated HIV testing and counseling acceptance. Health professionals working at outpatient department should give due attention to overcome these barriers so as to enhance HIV testing acceptance by their clients ." "JOURNAL ARTICLE"
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Predictors of Revision Surgery After Anterior Cruciate Ligament Reconstruction Arthroscopically assisted anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure. Graft failure after reconstruction remains a devastating complication, often requiring revision surgery and less aggressive or modified rehabilitation. Worse functional and patient-reported outcomes are reported compared with primary reconstruction. Moreover, both rates and risk factors for revision are variable and inconsistent within the literature. To determine the rate of revision surgery after ACL reconstruction in a large cohort of patients, to assess the influence of patient characteristics on the odds of revision, and to compare revision rates between active-duty military members and non-active-duty beneficiaries. Descriptive epidemiology study. Using administrative data from the Military Health System, a retrospective study was designed to characterize the rate of ACL revision surgery among patients treated within a military facility. All patients ≥18 years at the time of ACL reconstruction were identified using the American Medical Association Current Procedural Terminology (CPT) for ACL reconstruction (CPT code 29888) over 7 years (2005-2011). Revision ACL reconstructions were identified as having ≥2 ACL reconstruction procedure codes on the ipsilateral knee at least 90 days apart. Univariate analysis was performed to calculate odds ratios (ORs) for demographic, perioperative medication use, and concomitant procedure -related risk factors. A multivariate logistic regression model determined risk covariates in the active-duty cohort. The study population consisted of 17,164 ACL reconstruction s performed among 16,336 patients, of whom 83.3% were male with a mean ± SD age of 28.9 ± 7.6 years for the nonrevision group, and was predominantly active duty (89.2%). Patients undergoing ACL reconstruction on both knees only contributed their index knee for analyses. There were 587 patients who underwent revision surgery, corresponding to an overall revision rate of 3.6%. The median time from the index surgery to revision surgery was 500 days (interquartile range, 102-2406 days). Revision rates were higher in the active-duty cohort as compared with non-active-duty beneficiaries (3.8% vs 1.8%, respectively; OR, 2.14; 95% CI, 1.49-3.07). Based on multivariate logistic regression in the active-duty cohort, age ≥35 years (OR, 0.44; 95% CI, 0.33-0.58) and concomitant meniscal repair (OR, 0.69; 95% CI, 0.53-0.91) were found to be protective with regard to the odds of revision surgery. Perioperative medication use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 1.33; 95% CI, 1.12-1.58; number needed to harm [NNH], 100) and COX-2 inhibitors (OR, 1.31; 95% CI, 1.04-1.66; NNH, 333) was associated with increased odds of revision surgery. No significant findings were detected among sex, race, nicotine use, body mass index, or other concomitant procedures of interest. In this large cohort study, the rate of revision ACL reconstruction was 3.6%, which is consistent with the existing l iterature. Increased odds of revision surgery among active-duty personnel were associated with the perioperative use of NSAIDs and COX-2 inhibitors. Age ≥35 years and concomitant meniscal repair were found to be protective against ACL revision.
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[ 1871, 1875 ], [ 1876, 1883 ], [ 1884, 1886 ], [ 1887, 1890 ], [ 1891, 1896 ], [ 1897, 1899 ], [ 1900, 1904 ], [ 1905, 1908 ], [ 1909, 1918 ], [ 1918, 1919 ], [ 1920, 1926 ], [ 1927, 1940 ], [ 1941, 1948 ], [ 1949, 1953 ], [ 1954, 1958 ], [ 1959, 1961 ], [ 1962, 1970 ], [ 1971, 1974 ], [ 1975, 1979 ], [ 1980, 1991 ], [ 1992, 1994 ], [ 1995, 2005 ], [ 2006, 2014 ], [ 2015, 2023 ], [ 2024, 2026 ], [ 2027, 2035 ], [ 2036, 2038 ], [ 2039, 2047 ], [ 2048, 2056 ], [ 2057, 2064 ] ]
Country - specific chemical signatures of persistent organic pollutants (POPs) in breast milk of French, Danish and Finnish women The present study compares concentrations and chemical profiles of an extended range of persistent organic pollutants (dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in breast milk samples from French (n = 96), Danish (n = 438) and Finnish (n = 22) women. Median exposure levels observed in French women (WHO - TEQ 2005 PCDD/F = 6.1 pg/g l.w., WHO - TEQ 2005 dl-PCB = 4.3 pg/g l.w., sum of 6 ndl-PCB = 85.2 ng/g l.w., sum of 7 i-PBDE = 1.5 ng/g l.w.) appeared overall lower than in Danish and Finnish women for all examined POPs, except for α-HBCD (2-fold higher level at 0.6 ng/g l.w.). Furthermore, the observed exposure levels of dioxins and PCBs were higher in Danish women (WHO - TEQ 2005 PCDD/F = 13.2 pg/g l.w., WHO - TEQ 2005 dl-PCB = 6.6 pg/g l.w., sum of 6 ndl-PCB = 162.8 ng/g l.w.) compared to Finnish women (WHO - TEQ 2005 PCDD/F = 9.0 pg/g l.w., WHO - TEQ 2005 dl-PCB = 4.6 pg/g l.w., sum of 6 ndl-PCB = 104.0 ng/g l.w.), whereas the concentrations of PBDEs were similar for Danish and Finnish women (sum of 7 i-PBDE = 4.9 and 5.2 ng/g l.w. respectively). The organochlorine (OC) pesticide contamination profile, determined in a subset of French samples, was dominated by p,p'-DDE (56.6%), followed by β-HCH (14.2%), HCB (9.7%) and dieldrin (5.2%), while other compounds were only minor contributors (<5%). The three countries appeared to be discriminated by the observed contamination patterns of the PCDD/F versus PCB, and the 1,2,3,6,7,8-HxCDD versus 1,2,3,4,7,8-HxCDD ratios, in addition to the relative contributions of specific congeners to the contamination profile (PCBs #118 and #156, PBDEs #28, #47, #99 and #153). In conclusion, unique chemical signatures were observed for each country on the basis of some POP congeners. Future biomonitoring studies will need to consider the high variability of individual exposure profiles in relation to multiple exposure sources but also physiological and metabolic differences.
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Defining the sham environment for post-myocardial infarction studies in mice The purpose of this study was to evaluate the effect of sham surgery in a minimally invasive surgical model of permanent coronary artery occlusion used to generate myocardial infarction (MI) in mice. Adult male C57BL/6J mice (3-6 mo old) were divided into five groups: day (D) 0 (no surgical operation), D1 Sham, D1 MI, D7 Sham, and D7 MI. A refined MI surgery technique was used to approach the coronary artery without the ribs being cut. Both sham and MI mice had the left ventricle (LV) exposed through a small incision. To test the effects of surgery alone, the suture was passed around the coronary artery but not ligated. The MI mice were subjected to permanent coronary artery ligation. The mice were killed at D1 or D7 postsurgical procedure. Compared with D0 no surgery controls, the D1 and D7 sham groups exhibited no surgical mortality and similar necropsy and echocardiographic variables. Surgery alone did not induce an inflammatory cell response, as evidenced by the lack of leukocyte infiltration in the sham groups. Analysis of 165 inflammatory cytokines and extracellular matrix factors in sham revealed that a minor gene response was initiated but not translated to protein levels. Collagen deposition did not occur in the absence of MI. In contrast, the D1 and D7 MI groups showed the expected robust inflammatory and scar formation responses. When a minimally invasive procedure to generate MI in mice was used, the D0 (no surgical operation) control was an adequate replacement for the use of sham surgery groups.
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Core Privileging and Credentialing: Hospitals' Approach to Gynecologic Surgery Privileging and credentialing requirements are determined by medical staff leadership at the hospital level to ensure clinicians provide safe healthcare services. No standardized guidelines exist for gynecologic surgery. The objective of this study is to examine the variability of the criteria used to grant surgical privileges and credentials for gynecologic procedures at 5 high-volume academic and community-based US hospitals. We conducted a cross-sectional study (Canadian Task Force classification III). Data was obtained from obtained from 5 geographically diverse hospital systems. We examined criteria for designating core gynecologic privileges, credentialing, and other training requirements as well as minimum and annual case numbers for initial granting and maintenance of surgical privileges. Major inconsistencies in privileging were found alacross the 5 institutions. Hospitals varied widely in procedures designated as core versus those requiring advanced training. Institutions greatly contrasted in the case numbers and temporal factors used to define experience. Of particular concern was absent privileging criteria for 38.4% to 76.9% of minor procedures, 26.7% to 46.7% of endoscopic procedures, and 6.67% to 56.7% of major procedures. Initial and maintenance privileging requirements for special procedures (i.e., robotic-assisted surgery) were likewise discrepant, with minimum annual case numbers ranging from 3 to 48 across hospitals. Considerable variability exists in the criteria used by hospitals for granting and maintaining surgical privileges for gynecologic procedures. Standardization will likely require efforts at a national leadership level.
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Development and Validation of a 10-Year Mortality Prediction Model: Meta-Analysis of Individual Participant Data From Five Cohorts of Older Adults in Developed and Developing Countries Existing mortality prediction models for older adults have been each developed using a single study from the United States or Western Europe. We aimed to develop and validate a 10-year mortality prediction model for older adults using data from developed and developing countries. We used data from five cohorts, including data from 16 developed and developing countries: ELSA (English Longitudinal Study of Aging), HRS (Health and Retirement Study), MHAS (Mexican Health and Aging Study), SABE-Sao Paulo (The Health, Well-being and Aging), and SHARE (Survey on Health, Ageing and Retirement in Europe). 35,367 older adults were split into training (two thirds) and test (one third) data sets. Baseline predictors included age, sex, comorbidities, and functional and cognitive measures. We performed an individual participant data meta-analysis using a sex-stratified Cox proportional hazards model, with time to death as the time scale. We validated the model using Harrell's C statistic (discrimination) and the estimated slope between observed and predicted 10-year mortality risk across deciles of risk (calibration). During a median of 8.6 years, 8,325 participants died. The final model included age, sex, diabetes, heart disease, lung disease, cancer, smoking, alcohol use, body mass index, physical activity, self-reported health, difficulty with bathing, walking several blocks, and reporting date correctly. The model showed good discrimination (Harrell's C = 0.76) and calibration (slope = 1.005). Models for developed versus developing country cohorts performed equally well when applied to data from developing countries. A parsimonious mortality prediction model using data from multiple cohorts in developed and developing countries can be used to predict mortality in older adults in both settings.
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Outcomes of Subaortic Obstruction Resection in Children Studies of long-term outcomes of discrete subaortic stenosis are rare. Therefore, we reviewed the long-term outcomes of fibromuscular resection in children with subaortic stenosis over 26 years from a single institution. We conducted a retrospective review of all children (n=72) who underwent resection of subaortic obstruction for discrete subaortic stenosis between 1989 and 2015. Median age at surgery was 5.0 years (2.7-7.6 years). There were no operative deaths but three late deaths (4.2%, 3/72). Overall Kaplan-Meier survival at 10 years was 93.0 ± 3.9% (95% CI: 79.6, 97.7). Peak instantaneous left ventricular outflow tract Doppler gradient decreased from 74.2±36.7mmHg (16.0-242.0mmHg) preoperatively to 12.8±7.4mmHg (2.6-36.0mmHg) postoperatively (p<0.001). Mean left ventricular outflow tract Doppler gradient decreased from 42.4±17.2mmHg (12.0-98.0) preoperatively to 7.5±2.7mmHg (1.4-19.3mmHg) postoperatively (p<0.001). However, over the mean follow-up period of 7.8±6.1 years (0.1-25.2 years), 29.0% (20/69) of patients had recurrence and 18.8% (13/69) required reoperation at median time of 4.8 years (3.1-9.1 years) after the initial repair. Freedom from reoperation at 10 years was 71.1±7.1% (95% CI: 54.6, 82.3). Risk factors for reoperation were age less than five years at initial repair (p=0.036) and extension of the membrane to the aortic valve (p=0.001). Aortic insufficiency was present in 54.2% (39/72) of patients preoperatively. Progression of aortic insufficiency occurred in 38.9% (28/72). Involvement of the aortic valve at initial repair was associated with need for subsequent aortic valve repair or replacement (p=0.01). Resection of subaortic obstruction is associated with low mortality and morbidity. Recurrence and reoperation rates are high and progression of aortic insufficiency following subaortic resection is common. Therefore, these patients warrant close follow-up into adult life.
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Temperature and Plant Genotype Alter Alkaloid Concentrations in Ryegrass Infected with an Epichloë Endophyte and This Affects an Insect Herbivore Asexual Epichloë endophytes colonize agricultural forage grasses in a relationship which is mutually beneficial and provides the host plant with protection against herbivorous insects. The endophyte strain AR37 (Epichloë festucae var. lolii) produces epoxy-janthitrem alkaloids and is the only endophyte known to provide ryegrass with resistance against porina larvae (Wiseana cervinata (Walker)), a major pasture pest in cooler areas of New Zealand. This study examined the effect of temperature on concentrations of epoxy-janthitrems in AR37 - infected ryegrass and determined how the resulting variations in concentration affected consumption, growth and survival of porina larvae. Twenty replicate pairs of perennial (Lolium perenne L.) and Italian ryegrass (L. multiflorum Lam.) plants with and without endophyte were prepared by cloning, with one of each pair grown at either high (20°C) or low (7°C) temperature. After 10 weeks, herbage on each plant was harvested, divided into leaf and pseudostem, then freeze dried and ground. Leaf and pseudostem material was then incorporated separately into semi - synthetic diets which were fed to porina larvae in a bioassay over 3 weeks. Epoxy-janthitrem concentrations within the plant materials and the semi - synthetic diets were analyzed by high performance liquid chromatography. AR37 - infected ryegrass grown at high temperature contained high in plant a concentrations of epoxy-janthitrem (30.6 μg/g in leaves and 83.9 μg/g in pseudostems) that had a strong anti-feedant effect on porina larvae when incorporated into their diets, reducing their survival by 25-42% on pseudostems. In comparison, in planta epoxy-janthitrem concentrations in AR37 - infected ryegrass grown at low temperature were very low (0.67 μg/g in leaves and 7.4 μg/g in pseudostems) resulting in a small anti-feedant effect in perennial but not in Italian ryegrass. Although alkaloid concentrations were greatly reduced by low temperature this reduction did not occur until after 4 weeks of exposure. Alkaloid concentrations were slightly lower in Italian than in perennial ryegrass and concentrations were higher in the pseudostems when compared with the leaves. In conclusion, epoxy-janthitrems expressed by the AR37 endophyte show strong activity against porina larvae. However, when ryegrass plants are grown at a constant low temperature for an extended period of time in planta epoxy-janthitrem concentrations are greatly reduced and are less effective against this pasture pest.
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Three zinc-finger RNA-binding proteins in cabbage (Brassica rapa) play diverse roles in seed germination and plant growth under normal and abiotic stress conditions Despite the increasing understanding of the stress-responsive roles of zinc-finger RNA-binding proteins (RZs) in several plant species, such as Arabidopsis thaliana, wheat (Triticum aestivum) and rice (Oryza sativa), the functions of RZs in cabbage (Brassica rapa) have not yet been elucidated. In this study, the functional roles of the three RZ family members present in the cabbage genome, designated as BrRZ1, BrRZ2 and BrRZ3, were investigated in transgenic Arabidopsis under normal and environmental stress conditions. Subcellular localization analysis revealed that all BrRZ proteins were exclusively localized in the nucleus. The expression levels of each BrRZ were markedly increased by cold, drought or salt stress and by abscisic acid (ABA) treatment. Expression of BrRZ3 in Arabidopsis retarded seed germination and stem growth and reduced seed yield of Arabidopsis plants under normal growth conditions. Germination of BrRZ2 - or BrRZ3 - expressing Arabidopsis seeds was delayed compared with that of wild-type seeds under dehydration or salt stress conditions and cold stress conditions, respectively. Seedling growth of BrRZ3 - expressing transgenic Arabidopsis plants was significantly inhibited under salt, dehydration or cold stress conditions. Notably, seedling growth of all three BrRZ- expressing transgenic Arabidopsis plants was inhibited upon ABA treatment. Importantly, all BrRZs possessed RNA chaperone activity. Taken together, these results indicate that the three cabbage BrRZs harboring RNA chaperone activity play diverse roles in seed germination and seedling growth of plants under abiotic stress conditions as well as in the presence of ABA.
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Longitudinal Associations Between Cyberbullying Involvement and Adolescent Mental Health Cyberbullying differs from face-to-face bullying and may negatively influence adolescent mental health, but there is a lack of definitive research on this topic. This study examines longitudinal associations between cyberbullying involvement and adolescent mental health. Participants were 2,480 teenagers taking part in the Olympic Regeneration in East London study. We collected information from participants when they were 12-13 years old and again 1 year later to examine links between involvement in cyberbullying and future symptoms of depression and social anxiety, and mental well-being. At baseline, 14% reported being cybervictims, 8% reported being cyberbullies, and 20% reported being cyberbully-victims in the previous year. Compared to uninvolved adolescents, cybervictims and cyberbully-victims were significantly more likely to report symptoms of depression (cybervictims: odds ratio [OR] = 1.44, 95% confidence interval [CI] [1.00, 2.06]; cyberbully-victims: OR = 1.54, 95% CI [1.13, 2.09]) and social anxiety (cybervictims: OR = 1.52, 95% CI [1.11, 2.07]; cyberbully-victims: OR = 1.44, 95% CI [1.10, 1.89]) but not below average well-being (cybervictims: relative risk ratio = 1.28, 95% CI [.86, 1.91]; cyberbully-victims: relative risk ratio = 1.38, 95% CI [.95, 1.99]) at 1 year follow-up, after adjustment for confounding factors including baseline mental health. This study emphasizes the high prevalence of cyberbullying and the potential of cybervictimization as a risk factor for future depressive symptoms, social anxiety symptoms, and below average well-being among adolescents. Future research should identify protective factors and possible interventions to reduce adolescent cyberbullying.
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A proteomic evaluation of urinary changes associated with cardiopulmonary bypass The urinary proteome of patients undergoing cardiopulmonary bypass (CPB) may provide important insights into systemic and renal changes associated with the procedure. Such information may ultimately provide a basis to differentiate changes or properties associated with the development of acute kidney injury. While mass spectrometry (MS) analysis offers the potential for in-depth compositional analysis it is often limited in coverage and relative quantitation capacity. The aim of this study was to develop a process flow for the preparation and comparison of the intraoperative urinary proteome. Urines were collected from patients at the start of CPB and 1-h into CPB. Pooled samples (n = 5) from each time point were processed using a modified Filter Assisted Sample Preparation protocol. The resulting peptides were analyzed by 2D-LC-MS / MS and by 1D-LC-MS / MS SWATH (Sequential Window acquisition of All Theoretical fragment ion spectra). The 2D-LC-MS / MS analysis identified 1324 proteins in the two pools, of which 744 were quantifiable. The SWATH approach provided quantitation for 730 proteins, 552 of which overlapped with the common population from the 2D-IDA results. Intensity correlation filtering between the two methods gave 475 proteins for biological interpretation. Proteins displaying greater than threefold changes (>log2 1.59) at 1-hour CPB relative to the initiation of CPB (26 down-regulated and 22 up-regulated) were selected for further analysis. Up-regulated proteins were enriched in GO terms related to humoral immune response, predominantly innate immunity (C4b, lactotransferrin, protein S100-A8, cathelicidin, myeloperoxidase) and extracellular matrix reorganization (e.g. MMP-9). This study describes a scheme for processing urine from patients undergoing CPB for mass spectrometry -based analysis. The introduction of SWATH into the workflow offers a sample and instrument sparing approach to obtaining consistent in-depth sample analysis. The design of the methodology is such that it can be readily applied to large numbers of clinical samples with the potential for automation. The results also suggest that activation of the innate immune responses occur during cardiac bypass surgery.
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Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS - induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS - stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1 - 3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy.
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Drug-drug interactions of cytostatics with regular medicines in lung cancer patients Lung cancer patients have a high risk for drug-drug interactions, as they use numerous types of concomitant medicines including antineoplastic agents, cancer treatment co-medication, and medicines aimed at several types of comorbidities. The primary objective of this study is to determine the incidence and the clinical relevance of the drug-drug interactions between antineoplastic agents and regular medication used by lung cancer patients. Secondary objectives are (i) to determine the effectiveness of the medication review by the hospital pharmacists concerned, (ii) to establish which patients are most at risk of drug-drug interactions and (iii) to determine whether physicians comply with advice given by hospital pharmacists. This prospective study was undertaken in a Dutch hospital pharmacy, at Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. All lung cancer patients receiving one or more cytotoxic agents during the period 21 June 2010 till 2 December 2014 at OLVG were included. The medication list of the patients was obtained electronically from the community pharmacy and checked for interactions by a hospital pharmacist. Interactions that required intervention according to the national database were the only ones taken into account. Interventions were recorded in the patients ' electronic chart s. All medication reviews were cross-checked and analyzed by an independent pharmacist at the end of the study period. Prevalence and clinical relevance of drug-drug interactions between antineoplastic agents and other types of medication in lung cancer patients. A total of 298 lung cancer patients were included in this study. In 53 patients (18%), a total of 73 interactions with potential clinical relevance were found. The most frequent interaction was between cytostatics and coumarins while the most relevant one was between cisplatin and furosemide. According to statistical analysis, gender as well as the number of drugs prescribed were significant predictors for drug-drug interactions. Eighty-four percent of the interactions were discovered by pharmacists during daily routine. In 92% of the cases, the pulmonary physicians complied with the advice of the pharmacist. Eighteen percent of lung cancer patients treated with cytotoxic therapy had one or more relevant drug-drug interactions. This study shows that medication surveillance by a hospital pharmacist is necessary to prevent possible negative drug-drug interactions. Further research should focus on the clinical outcome of the interactions as well as on interactions between cytostatics and alternative medicines and/or over-the-counter medicines.
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Relation of Plasma Lipoprotein(a) to Subclinical Coronary Plaque Volumes, Three-Vessel and Left Main Coronary Disease, and Severe Coronary Stenoses in Apparently Healthy African-Americans With a Family History of Early-Onset Coronary Artery Disease Serum lipoprotein(a) [Lp(a)] is a coronary artery disease (CAD) risk factor in persons of European ancestry. Levels are twofold to threefold higher in African-Americans (AAs), but reported associations with CAD have been inconsistent. The relation of Lp(a) with the extent and severity of subclinical coronary plaque has not been described in AAs. We screened 269 apparently healthy AAs for risk factors and coronary plaque using advanced coronary computed tomographic angiography. Total coronary plaque (TCP), noncalcified coronary plaque, and calcified coronary plaque volumes (mm(3)) were quantified using a validated automated method. Lp(a) was measured by ELISA. Multivariable modeling was performed with adjustment for traditional CAD risk factors and intrafamilial correlations. Mean age was 51 ± 11 years and 64% were female. Plaque was present in 41%. Lp(a) was independently associated with TCP volume [log(TCP + 1)] (p = 0.04), 3-vessel and/or left main involvement (p = 0.04), and at least 1 stenosis >50% (p = 0.006). Best-fit regression analyses showed that subjects with Lp(a) >40 mg/dl were threefold more likely to have 3-vessel and/or left main disease (95% confidence interval 1.4 to 6.8, p = 0.005) and fourfold more likely to have stenosis >50% (95% confidence interval 1.3 to 15.0, p = 0.02). In subjects with plaque (n = 110), multivariable models showed the Lp(a) level was significantly and independently associated with TCP (p = 0.009), noncalcified coronary plaque (p = 0.01), and calcified coronary plaque (p = 0.003) and affected vessel length (p = 0.01). In conclusion, high Lp(a) is strongly associated with coronary plaque volumes, extent, and severity in apparently healthy AAs. High levels of Lp(a) may be particularly important in the pathogenesis of CAD in AAs.
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Palliative care in mental health facilities from the perspective of nurses: a mixed-methods study WHAT IS KNOWN ON THE SUBJECT?: Nurses play an important role in monitoring and supporting patients and their relatives at the end of life. To date, there is a lack of recent empirical research on the experiences of psychiatric nurses in providing palliative care to psychiatric patients who suffer from life-threatening physical co-morbidity. The limited literature available indicates that palliative care for psychiatric patients needs to be improved. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This explorative study is unique in offering an insight into current palliative care practice for psychiatric patients and showed that one in three nurses working in Dutch mental health facilities is involved in palliative care provision. Important elements of palliative care, i.e.: care domains, multidisciplinary approach, early recognition and family care are recognized by nurses. Moreover, in palliative care for psychiatric patients there is more attention for psychosocial and spiritual care compared to palliative care for patients without psychiatric disorders. Patient characteristics and little attention for palliative care within mental health facilities were found to hamper timely and adequate palliative care provision by nurses. WHAT ARE THE IMPLICATIONS FOR RESEARCH AND PRACTICE?: Educating psychiatric nurses about palliative care and close collaboration between physical and mental health care are crucial to address the palliative care needs of this vulnerable patient group. Since mental health care is increasingly provided ambulatory, the development of palliative care for psychiatric patients outside mental health facilities should be closely monitored. Introduction Recent empirical research on palliative care for psychiatric patients is lacking. Aim The aim of this study was to explore nurses ' experiences with and identify barriers to providing palliative care to psychiatric patients in Dutch mental health facilities. Methods Mixed-methods; 137 nurses working in Dutch mental health facilities completed a survey. Nine participated in in-depth interviews. Results Thirty-six percent of nurses had experience with providing palliative care to psychiatric patients with physical co-morbidity in the past 2 years. Of all patients, 63% received physical care before death, 46% psychosocial care and 33% spiritual care. In 91% of all cases, care was provided by multidisciplinary teams. Patient characteristics and little attention to palliative care were barriers for timely and adequate palliative care. Discussion In palliative care for psychiatric patients, there is more attention for psychosocial and spiritual care compared to palliative care for patients without psychiatric disorders. Yet there are barriers to adequate palliative care provision. Implications for practice Educating psychiatric nurses about palliative care and close collaboration between physical and mental health care are crucial to address the palliative care needs of psychiatric patients. Since mental health care is increasingly provided ambulatory, palliative care for psychiatric patients outside mental health facilities should be closely monitored.
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Untoward events associated with aberrant fluid infusion during cataract surgery: Laboratory study with corroborative clinical observations To determine the relationship between untoward events noted during phacoemulsification surgery associated with aberrant infusion misdirection and their causal relationship to current infusion sleeve design. The New York Eye & Ear Infirmary of Mt. Sinai, New York, New York, USA. Retrospective case reports and experimental study. Observations of live cataract surgery were documented with high-definition videography using 3 commercial phacoemulsification platforms. Laboratory studies using a Photron MC2 high-speed camera and the Kitaro cataract surgical system were used to simulate surgical maneuvers and assess flow patterns and visualize the dynamics of fluid movement in the anterior chamber. Color-flow Doppler ultrasound studies were used to demonstrate the effect of infusion fluid on the iris during surgery. Misdirected infusion and floppy-iris leaflets were determined to be secondary to a fulcrum effect at the corneal wound that constrained movement of the standard silicone sleeves. The phacoemulsification needles could therefore decenter independently of the infusion sleeve, attenuating infusion volume down 1 side of the sleeve and, as a result, obstructing fluid exiting the ipsilateral port. Untoward events associated with aberrant fluid infusion during phacoemulsification surgery were secondary to a fulcrum effect at the corneal wound. Complications included misdirected infusion that facilitated the transport of retained nuclear fragments to the vitreous, inconsistent lens followability during phacoemulsification, and exaggerated movements of the iris particularly consistent with intraoperative floppy-iris syndrome and pseudoexfoliation. None of the authors has a financial or proprietary interest in any material or method mentioned.
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Self-Cloning CRISPR CRISPR/Cas9 - gene editing has emerged as a revolutionary technology to easily modify specific genomic loci by designing complementary sgRNA sequences and introducing these into cells along with Cas9. Self-cloning CRISPR/Cas9 (scCRISPR) uses a self-cleaving palindromic sgRNA plasmid (sgPal) that recombines with short PCR - amplified site-specific sgRNA sequences within the target cell by homologous recombination to circumvent the process of sgRNA plasmid construction. Through this mechanism, scCRISPR enables gene editing within 2 hr once sgRNA oligos are available, with high efficiency equivalent to conventional sgRNA targeting: >90% gene knockout in both mouse and human embryonic stem cells and cancer cell lines. Furthermore, using PCR-based addition of short homology arms, we achieve efficient site-specific knock-in of transgenes such as GFP without traditional plasmid cloning or genome-integrated selection cassette (2% to 4% knock-in rate). The methods in this paper describe the most rapid and efficient means of CRISPR gene editing. © 2016 by John Wiley & Sons, Inc. Journal Article 2016-08-18 00:00:00
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Contemporary use of ticagrelor in patients with acute coronary syndrome: insights from Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) The platelet inhibitor ticagrelor is strongly recommended during 12 months post - acute coronary syndrome (ACS) in European guidelines. We analysed clinical characteristics of patients given ticagrelor for ACS in the real world. We studied the use of ticagrelor in patients admitted for ACS in Sweden between 1 January 2012 and 31 December 2013 who were enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Clinical characteristics were investigated for patients prescribed ticagrelor at discharge as well as for patients undergoing percutaneous coronary intervention who were prescribed ticagrelor. Independent factors associated with selecting ticagrelor were analysed in logistic regression. We found that 44.0% (n = 12 601) out of a total of 28 639 patients had been prescribed ticagrelor at discharge. After adjusting for age and sex, prior cardiovascular disease was less common in patients discharged on ticagrelor (myocardial infarction, ischaemic stroke, and peripheral vascular disease; P for all <0.001). The risk of death as predicted by GRACE score and the risk of major bleeding as predicted by CRUSADE score were both lower in ticagrelor - treated patients vs. others (median 99 vs. 126 and median 23 vs. 25, respectively; P for both < 0.001). The intended treatment duration at discharge was 12 months in 82.5% of patients and <12 months in 9.3%. Ticagrelor is preferentially being used in patients at lower risk. A minority of patients are recommended ticagrelor during <12 months.
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Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells Diversity within the p53 transcriptional network can arise from a matrix of changes that include target response element sequences and p53 expression level variations. We previously found that wild type p53 (WT p53) can regulate expression of most innate immune -related Toll-like-receptor genes (TLRs) in human cells, thereby affecting immune responses. Since many tumor-associated p53 mutants exhibit change-of-spectrum transactivation from various p53 targets, we examined the ability of twenty-five p53 mutants to activate endogenous expression of the TLR gene family in p53 null human cancer cell lines following transfection with p53 mutant expression vectors. While many mutants retained the ability to drive TLR expression at WT levels, others exhibited null, limited, or change-of-spectrum transactivation of TLR genes. Using TLR3 signaling as a model, we show that some cancer -associated p53 mutants amplify cytokine, chemokine and apoptotic responses after stimulation by the cognate ligand poly(I:C). Furthermore, restoration of WT p53 activity for loss-of-function p53 mutants by the p53 reactivating drug RITA restored p53 regulation of TLR3 gene expression and enhanced DNA damage-induced apoptosis via TLR3 signaling. Overall, our findings have many implications for understanding the impact of WT and mutant p53 in immunological responses and cancer therapy.
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Nursing ancestry now easier to trace as RCN records are published online Records of more than 1.5 million nurses dating back 125 years have been digitised for the first time.
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Olive oil's extra benefits Could a Mediterranean diet including extra virgin olive oil reduce the risk of breast cancer? Niki Mourouti and Demosthenes Panagiotakos ' study in Evidence Based Nursing examined the effects on cancer risks of a Mediterranean diet supplemented with extra virgin olive oil.
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Steroid Sulfates from Ophiuroids (Brittle Stars): Action on Some Factors of Innate and Adaptive Immunity The action of seven polyhydroxylated sterol mono- and disulfates (1-7), isolated from ophiuroids, on innate and adaptive immunity was examined in in vitro and in vivo experiments. At least, three of them (1, 2 and 4) increased the functional activities of neutrophils, including levels of oxygen - dependent metabolism, adhesive and phagocytic properties, and induced the expression of pro-inflammatory cytokines TNF-α and IL-8. Compound 4 was the most active for enhancing the production of antibody forming cells in the mouse spleen.
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Mobility Experience of Persons with Visual Impairments in Indian Railway Station Environments Mobility for persons with visual impairments in Indian railway stations poses multidimensional challenges for access to an inclusive travel experience. India is a home to about twenty million persons with diverse disabilities out of which about five million are persons with visual impairments. Diversity of passenger movements on a railway station including persons with visual impairments requires a Universal Design approach to respond to the accessibility issues in these contexts. This research study is based on a series of live on-site experiences conducted along with persons with visual impairments at New Delhi Railway Station. It also includes the generic studies carried out with other diversities of railway passengers including aging, gender and diverse physical abilities. It employs research methods like ethnography, focus group interactions and trace study to develop a deeper understanding of human and spatial parameters of mobility in railway station environments. A Universal Design perspective with a holistic understanding remains critical to the foundation of this research study. While it deals in specific requirements of persons with visual impairments, it also brings an illustration of handling diversity on a railway station from a unique Indian perspective. It concludes by highlighting and reinterpreting the Universal Design India Principles integrating the needs of persons with visual impairments in railway station environments. Brief recommendation for an inclusive mobility experience on railway station forms a vital part of this grounded research study.
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2016 Updated MASCC / ESMO consensus recommendations: Management of nausea and vomiting in advanced cancer The aim of this paper is to review the existing literature related to the management of nausea and vomiting (N & V) in advanced cancer and derive clinical evidence -based recommendations for its management. Available systematic reviews on antiemetic drug effectiveness were used. One generic systematic review of antiemetics in advanced cancer (to 2009) was updated to February 2016. Agreement on recommendations was reached between panel members, and these were voted in favor unanimously by the larger antiemetic committee membership (n = 37). The evidence base in this field is minimal with largely poor quality trials or uncontrolled trials and case studies. The level of evidence in most studies is low. The drug of choice for managing N & V in advanced cancer is metoclopramide titrated to effect. Alternative options include haloperidol, levomepromazine, or olanzapine. For bowel obstruction, the recommendation is to use octreotide given alongside an antiemetic (haloperidol) and where octreotide is not an option to use an anticholinergic antisecretory agent. For opioid - induced N & V, no recommendation could be made. These new guidelines, based on the existing (but poor) evidence, could help clinicians manage more effectively the complex and challenging symptoms of N & V in advanced cancer.
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Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models 1. Hesperetin (HDND) possesses extensive bioactivities, however, its poor solubility and low bioavailability limit its application. HDND-7, a derivative of HDND, has better solubility and high bioavailability. In this study, we investigated the intestinal absorption mechanisms of HDND-7. 2. MDCK cells were used to examine the transport mechanisms of HDND-7 in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of HDND-7. The concentration of HDND-7 was determined by HPLC. 3. In MDCK cells, HDND-7 was effectively absorbed in a concentration - dependent manner in both directions. Moreover, HDND-7 showed pH - dependent and TEER - independent transport in both directions. The transport of HDND-7 was significantly reduced at 4 °C or in the presence of NaN3. Furthermore, the efflux of HDND-7 was apparently reduced in the presence of MRP2 inhibitors MK-571 or probenecid. However, P-gp inhibitor verapamil had no effect on the transport of HDND-7. The in situ intestinal perfusion study indicated HDND-7 was well-absorbed in four intestinal segments. Furthermore, MRP2 inhibitors may slightly increase the absorption of HDND-7 in jejunum. 4. In summary, all results indicated that HDND-7 might be absorbed mainly by passive diffusion via transcellular pathway, MRP2 but P-gp may participate in the efflux of HDND-7.
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RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients ' specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin - induced apoptosis by RBBP6 targeting suggests a promising tool for halting cervical cancer progression.
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The Modified 3-square Flap Method for Reconstruction of Toe Syndactyly Bandoh reported the 3-square-flap method as a procedure for interdigital space reconstruction in patients with minor syndactyly. We recently modified this flap design so that it could be used in the treatment of toe syndactyly involving fusion of the areas distal to the proximal interphalangeal joint. With our method, the reconstructed interdigital space consists of 4 oblong flaps (A through D). Flaps A and D are designed on the dorsal side, flap B is designed on the frontal plane of the interdigital space, and flap C is designed on the plantar side. Flaps A, B, and C are raised immediately below the dermis in a manner that allowed slight fat tissue to adhere to each flap. Flap D is freed to a degree minimally needed for dislocation, while leaving a thick subcutaneous pedicle. Flaps A, B, and C are each folded in 90 degrees; flap D is dislocated to the proximal plane of the reconstructed digit, followed by skin suturing. In this process, suturing is avoided between flaps A and C, between flaps A and D, and between flaps B and D. During the period of 2011 to 2015, we treated 8 patients of toe syndactyly involving fusion distal to the proximal interphalangeal joint. Cases of congenital syndactyly received surgery between the ages of 8 and 11 months. Using this technique, flap ischemia / necrosis was not observed. During the postoperative follow-up period, the interdigital space retained sufficient depth without developing any scar contracture. No case required additional surgery.
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Multicenter Trial of Rivaroxaban for Early Discharge of Pulmonary Embolism From the Emergency Department (MERCURY PE): Rationale and Design Traditionally, patients with pulmonary embolism (PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment. We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome. Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board. The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study.
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The Development and Psychometric Properties of the Children's Sleep Assessment Questionnaire in Taiwan To develop and examine the validity and reliability of the Children's Sleep Assessment Questionnaire (CSAQ) for school-aged children in Taiwan. We used a cross-sectional study design with stratified random sampling. Pairs of children and parents were recruited from a school -based sample of third- and fourth-grade students, enrolling 362 child and parent pairs. The content validity, construct validity, convergent validity, internal consistency, and inter-rater reliability of the CSAQ were assessed. The CSAQ comprised three parts: sleep hygiene, sleep quality, and sleep disturbance. Sleep hygiene showed a moderate intra-class correlation coefficient (0.37-0.66) between children and parents. Results of exploratory factor analysis suggested a four-factor structure model for sleep quality with 64.9% of variance and a two-factor structure for sleep disturbance with 57.7% of variance. These two models also demonstrated good fit with the confirmatory factor analysis. The CSAQ is a valid and reliable instrument for assessing sleep problems in school-aged children. Both clinicians and researchers can use the CSAQ to screen or elucidate the children ' sleep problems.
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Altered Effects of Perspective-Taking on Functional Connectivity during Self- and Other-Referential Processing in Adults with Autism Spectrum Disorder In interactive social situations, it is often crucial to be able to take another person's perspective when evaluating one's own or another person's specific trait; individuals with ASD critically lack this social skill. To examine how perspective - dependent self- and other- evaluation processes modulate functional connectivity in ASD, we conducted an fMRI study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself (" self ") or the participant's mother ("other") by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD.
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Effects of Smoke Generated by Electrocautery on the Larynx The aim of this study was to investigate effects of smoke produced by electrocautery on the laryngeal mucosa. We used 16 healthy, adult female Wistar albino rats. We divided the rats into two groups. Eight rats were exposed to smoke for 60 min/d for 4 weeks, and eight rats were not exposed to smoke and served as controls. The experimental group was maintained in a plexiglass cabin during exposure to smoke. At the end of 4 weeks, rats were sacrificed under high-dose ketamine anesthesia. Each vocal fold was removed. An expert pathologist blinded to the experimental group evaluated the tissues for the following: epithelial distribution, inflammation, hyperplasia, and metaplasia. Mucosal cellular activities were assessed by immunohistochemical staining for Ki67. Results taken before and after effect were compared statistically. There was a significant difference in the extent of inflammation between the experimental group and the control group. Squamous metaplasia was detected in each group, but the difference was not significant. None of the larynges in either group developed hyperplasia. We showed increased tissue inflammation due to irritation by the smoke.
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7-Hydroxytropolone produced and utilized as an iron - scavenger by Pseudomonas donghuensis Pseudomonas donghuensis can excrete large quantities of iron chelating substances in iron-restricted environments. At least two kinds of iron - chelator can be found in the culture supernatant: fluorescent siderophores pyoverdins, and an ethyl acetate -extractable non-fluorescent substance. The non-fluorescent substance was the dominant contributor to the iron chelating activity of the culture supernatant of P. donghuensis. Electron ionization mass spectrometry, NMR spectroscopy, and IR spectroscopy identified the non-fluorescent iron - chelator as 7-hydroxytropolone. The stoichiometry of 7-hydroxytropolone ferric complex was determined to be 2:1 by the continuous variation method. The production of 7-hydroxytropolone was repressible by iron in the medium. Moreover, the inhibited growth of doubly siderophore-deficient strain of P. donghuensis under iron-limiting conditions could be partly restored by 7-hydroxytropolone. Thus, 7-hydroxytropolone was considered to play a previously undiscovered role as an iron - scavenger for P. donghuensis.
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Drivers' eye movements as a function of collision avoidance warning conditions in red light running scenarios The intersection collision avoidance warning systems (ICAWSs) have substantial potentials in improving driving performance and reducing the number and severity of intersection collisions, through helping drivers timely detect hazardous conflicting vehicles in precrash scenarios. However, the influences of ICAWS on drivers' visual performance have barely been discussed. This study focuses on exploring the patterns in drivers' eye movements as a function of ICAWS's warning conditions in red light running scenarios based on a driving simulation experiment. Two types of speech warning conditions including warning timings (varied form 2.5s to 5.5s) and directional information (with or without) are examined, and the no - warning condition is the baseline. The results revealed that more subjects would be likely to benefit from the ICWAS under the earlier warning timings. The warning condition of 4.5s ahead of a collision had the best effectiveness in terms of visual performances. Under such a warning timing, drivers had shorter fixation duration and higher frequency of searching for the red light running (RLR) vehicles. Compared to the warning condition without directional information, the directional warning information could capture drivers' attention more efficiently, help driver direct fixations toward the RLR vehicles more quickly and lead to more scanning activities. Compared to female drivers, male drivers had more scanning activities when approaching intersections, detected the RLR vehicles more quickly and were more likely to avoid the RLR collisions. Besides, the experiment results indicated that the female drivers were more inclined to trust the warning information and got more benefits from the RLR - ICAWS in terms of the crash risk reduction rate than male drivers. Finally, the conclusions lead the way toward warning condition design recommendations for improving the effectiveness of the RLR - ICAWSs.
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An electrochemically reduced graphene oxide chemiresistive sensor for sensitive detection of Hg(2+) ion in water samples Divalent mercuric (Hg(2+)) ion is one of the most prevalent forms of mercury species in waters with high toxicity and bioaccumulation in the human body, for which sensitive and selective detection methods are highly necessary to carry out its recognition and quantification. Here an electrochemically reduced graphene oxide (RGO) based chemiresistive sensor was constructed and used for the detection of Hg(2+) ion in various water samples. Monolayer GO sheets were assembled onto interdigitated electrodes, followed by reduction through linear sweep voltammetry and then modification with a single-stranded DNA aptamer. The electrochemically derived RGO based sensor showed selective response to as low as 0.5nM Hg(2+) ion in presence of other metal ions and matrices. A comparison between chemiresistive sensors prepared with electrochemically and chemically derived RGO showed that the former had better response performance for sensing Hg(2+) ion. The proposed method provides a simple tool for rapid, selective and sensitive monitoring of Hg(2+) ion in environmental samples.
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The Effect of Image Review before Patient Discharge on Study Completeness and Sonographer Job Satisfaction in a Pediatric Echocardiographic Laboratory Incomplete echocardiographic assessment accounts for approximately 10% of preventable diagnostic errors and may place children at risk for adverse outcomes or increased testing. The aim of this study was to determine if physician review of images improves study completeness. A prospective quality improvement (QI) study initiated physician review of first-time echocardiographic studies for completeness before patient discharge. Studies were incomplete if not all anatomic structures were diagnostically demonstrated. QI examinations were compared with controls obtained before study initiation. Demographic and clinical information and duration of scan were collected during the control and QI periods. An anonymous survey was administered to the sonographers to assess perceptions of the intervention. There were no differences between the QI (n = 63) and control (n = 63) groups in age, height, weight, and technical barriers. After study completion, 35% of control scans versus 5% of QI scans were incomplete (P < .001). In the QI group, the sonographer, physician, or both returned to scan in 12 (19%), nine (14%), and two (3%) studies, respectively. QI studies were longer than control studies (44 vs 36 min, P = .003) before review. Physician review added a median of 6 min (range, 1-28 min). The majority of sonographers believed that immediate review improved communication, and 50% believed that it improved their job satisfaction. Review of initial outpatient echocardiographic examinations before patient discharge significantly improves study completeness. Review adds a nominal amount of time to total study duration, improves sonographer - physician communication, and may prevent unnecessary testing, potentially reducing the cost of care.
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Gastrocnemius muscle-tendon interaction during walking in typically-developing adults and children, and in children with spastic cerebral palsy Our understanding of the interaction of muscle bellies and their tendons in individuals with muscle pathology is limited. Knowledge of these interactions may inform us of the effects of musculoskeletal pathologies on muscle-tendon dynamics and the subsequent neurological control strategies used in gait. Here, we investigate gastrocnemius muscle-tendon interaction in typically-developing (TD) adults and children, and in children with spastic cerebral palsy (SCP). We recruited six TD adults (4 female; mean age: 34 yrs. (24-54)), eight TD children (5 female; mean age: 10 yrs. (6-12)) and eight independently ambulant children with SCP (5 female; mean age 9 yrs. (6-12); 3 unilaterally-affected). A combination of 3D motion capture and 2D real-time ultrasound imaging were used to compute the gastrocnemius musculo-tendinous unit (MTU) length and estimate muscle belly and tendon length s during walking. For the TD subjects, the measurements were made for heel-toe walking and voluntary toe-walking. The gastrocnemius muscle bellies of children with SCP lengthened during single support (p = 0.003). In contrast, the muscle bellies of TD subjects did not demonstrate an increase in length over the period of single support under heel-toe or toe-walking conditions. We observed lengthening of the gastrocnemius muscle bellies in children with SCP during single support, a phase of the gait cycle in which the muscle is reported consistently to be active. Repeated lengthening of muscle bellies while they are active may lead to muscle damage and have implications for the natural history of gait in this group.
[ "O", "O", "O", "O", "O", "O", "O", "B-T082", "O", "O", "O", "O", "O", "B-T082", "B-T170", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-T037", "I-T037", "I-T037", "O", "O", "B-T170", "I-T170", "I-T170", "O", "O", "B-T062", "I-T062" ]
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Dramatic demographic changes in spine trauma mortality over the past quarter century in Finland Commentary On: Thesleff T, Niskakangas T, Luoto TM, Öhman J, Ronkainen A. Fatal cervical spine injuries: a Finnish nationwide register -based epidemiological study on data from 1987 to 2010. Spine J 2016:16:918-26 (in this issue).
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Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP - pesticide interaction effects, we also performed exploratory analyses of gene- pesticide interactions at the gene level. None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP - level tests; α = 2.1E-06 for gene - level tests). Top results in the SNP - level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene - level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene - pesticide interactions reached statistical support in this genome-wide screen. Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.
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High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice Human pancreatic polypeptide (hPP) is known to suppress appetite and food intake, thereby representing a potential therapeutic approach against obesity and associated metabolic disorders. The aim of this study was to improve hPP stability by covalent PEGylation with diverse molecular weight polyethylene glycols (PEGs) at two positions using promising lead structures while maintaining target activity. Modified peptides were synthesized by combined solid-phase and solution-phase peptide synthesis. Their potency was investigated in constitutively expressing human epithelial cells and isolated human colonic mucosa as well as receptor-transfected artificial cell lines. Human blood plasma and porcine liver homogenates were used to examine the in vitro stability of the analogues. The most promising variants were injected s.c. in C57BL/6JRj mice to monitor fasting-induced food intake and bioavailability. In human epithelia and colonic mucosal preparations, activity of the modified hPP peptides depended on the core sequence and latency of the peptides was related to PEG size. Peptides modified with a 22 kDa PEG (PEG22) remained intact in blood plasma and on incubation with liver homogenates for more than 96 h. Finally, hPP2-36, [K(22) (PEG22)] hPP2-36 and [K(22) (PEG22),Q(34)] hPP significantly reduced cumulative food intake in mice over 16 h after s.c. administration. Modification with PEG22 at position 22 stabilizes hPP significantly while extending its biological activities and could be used in drug development prospectively.
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Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography / tandem mass spectrometry A remediable cause of poor treatment response in drug - susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first-line anti-TB drugs. The aim of this work was to develop an accurate and precise LC-MS / MS method for simultaneous quantification of all four first-line anti-TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed-Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5-10 mg/L, for rifampicin 0.75-30 mg/L, for ethambutol 0.25-10 mg/L and for pyrazinamide 4-80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC-MS / MS method can readily be used for simultaneous quantification of first-line anti-TB drugs in plasma and is well suited for TDM.
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The relationship between social functioning and subjective memory complaints in older persons: a population -based longitudinal cohort study Poor social functioning is associated with cognitive decline in older adults. It is unclear whether social functioning is also associated with subjective memory complaints (SMC). We investigated the association between social functioning and incident SMC and SMC recovery. A population -based sample of 8762 older adults (aged ≥65 years) with good objective cognitive functioning at baseline (MMSE ≥26) from the LifeLines Cohort Study were followed for 1.5 years. Self-reported SMC were measured at baseline and after 1.5 years follow-up. Aspects of social functioning included marital status, household composition, social network size, social activity, quality of social relationships, social support, affection, behavioral confirmation, and status. Thirteen percent (513/3963) developed SMC during follow-up (incident SMC). Multivariate logistic regression analyses (adjusted for age, gender, education level, physical activity, alcohol use, smoking status, depression, arrhythmia, myocardial infarction, heart failure, stroke) showed that participants with better feelings of affection, behavioral confirmation and stable good social support had a lower risk of incident SMC. Thirty-four percent (1632/4799) reported recovery. Participants with good social functioning at baseline on all determinants reported more SMC recovery. People who remained stable in a relationship, stable in good quality of social relationships or increased in quality of social relationships more often report SMC recovery. Good social functioning is associated with less incident SMC and more SMC recovery over a follow-up period of 1.5 years. Albeit future confirmative studies are needed, we argue for targeting also social functioning when designing multidomain interventions to prevent or slow down cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.
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Fitness implications of seasonal climate variation in Columbian ground squirrels The influence of climate change on the fitness of wild populations is often studied in the context of the spring onset of the reproductive season. This focus is relevant for climate influences on reproductive success, but neglects other fitness -relevant periods (e.g., autumn preparation for overwintering). We examined variation in climate variables (temperature, rainfall, snowfall, and snowpack) across the full annual cycle of Columbian ground squirrels (Urocitellus columbianus) for 21 years. We investigated seasonal climate variables that were associated with fitness variables, climate variables that exhibited directional changes across the study period, and finally observed declines in fitness (-0.03 units/year; total decline = 37%) that were associated with directional changes in climate variables. Annual fitness of adult female ground squirrels was positively associated with spring temperature (r = 0.69) and early summer rainfall (r = 0.56) and negatively associated with spring snow conditions (r = -0.44 to -0.66). Across the 21 years, spring snowmelt has become significantly delayed (r = 0.48) and summer rainfall became significantly reduced (r = -0.53). Using a standardized partial regression model, we found that directional changes in the timing of spring snowmelt and early summer rainfall (i.e., progressively drier summers) had moderate influences on annual fitness, with the latter statistically significant (ρ = -0.314 and 0.437, respectively). The summer period corresponds to prehibernation fattening of young and adult ground squirrels. Had we focused on a single point in time (viz. the onset of the breeding season), we would have underestimated the influences of climate change on our population. Rather, we obtained a comprehensive understanding of the influences of climate change on individual fitness by investigating the full lifecycle.
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Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal area s, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior / anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis.
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Flash visual evoked potentials in diurnal birds of prey The objective of this pilot study was to evaluate the feasibility of Flash Visual Evoked Potentials (FVEPs) testing in birds of prey in a clinical setting and to describe the protocol and the baseline data for normal vision in this species. FVEP recordings were obtained from 6 normal adult birds of prey: n. 2 Harris's Hawks (Parabuteo unicinctus), n. 1 Lanner Falcon (Falco biarmicus), n. 2 Gyrfalcons (Falco rusticolus) and n. 1 Saker Falcon (Falco cherrug). Before carrying out VEP tests, all animals underwent neurologic and ophthalmic routine examination. Waveforms were analysed to identify reproducible peaks from random variation of baseline. At least three positive and negative peaks were highlighted in all tracks with elevated repeatability. Measurements consisted of the absolute and relative latencies of these peaks (P1, N1, P2, N2, P3, and N3) and their peak-to-peak amplitudes. Both the peak latency and wave morphology achieved from normal animals were similar to those obtained previously in other animal species. This test can be easily and safely performed in a clinical setting in birds of prey and could be useful for an objective assessment of visual function.
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Acute Kinematic and Kinetic Adaptations to Wearable Resistance During Sprint Acceleration Macadam, P, Simperingham, KD, and Cronin, JB. Acute kinematic and kinetic adaptations to wearable resistance during sprint acceleration. J Strength Cond Res 31(5): 1297-1304, 2017- Wearable resistance (WR) in the form of weighted vests and shorts enables movement-specific sprint running to be performed under load. The purpose of this study was to determine the acute changes in kinematics and kinetics when an additional load equivalent to 3% body mass (BM) was attached to the anterior or posterior surface of the lower limbs during sprint running. Nineteen male rugby athletes (age: 19.7 ± 2.3 years; body mass: 96.1 ± 16.5 kg; height: 181 ± 6.5 cm) volunteered to participate in the study. Subjects performed six 20 m sprints in a randomized fashion wearing no resistance or 3% BM affixed to the anterior (quadriceps and tibialis anterior) or posterior (hamstring and gastrocnemius) surface of the lower limbs (2 sprints per condition). Optojump and radar were used to quantify sprint times, horizontal velocity, contact and flight times, and step length and frequency. A repeated measures analysis of variance with post hoc contrasts was used to determine differences (p ≤ 0.05) between conditions. No significant differences were found between the anterior and posterior WR conditions in any of the variables of interest. There was no significant change in sprint times over the initial 10 m, however, the 10-20 m split times were significantly slower (-2.2 to -2.9%) for the WR conditions compared with the unloaded sprints. A significant change in the relative force-velocity (F-v) slope (-10.5 to -10.9%) and theoretical maximum velocity (V0) (-5.4 to -6.5%) was found, whereas a nonsignificant increase in theoretical maximum force (F0) (4.9-5.2%) occurred. Wearable resistance of 3% BM may be a suitable training modality to enhance sprint acceleration performance by overloading the athlete without negatively affecting sprint running technique.
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[ 1736, 1743 ], [ 1744, 1754 ], [ 1755, 1758 ], [ 1759, 1763 ], [ 1764, 1774 ], [ 1774, 1775 ], [ 1776, 1784 ], [ 1785, 1791 ] ]
Perceptual Learning in Children With Infantile Nystagmus: Effects on Visual Performance To evaluate whether computerized training with a crowded or uncrowded letter-discrimination task reduces visual impairment (VI) in 6- to 11- year-old children with infantile nystagmus (IN) who suffer from increased foveal crowding, reduced visual acuity, and reduced stereopsis. Thirty-six children with IN were included. Eighteen had idiopathic IN and 18 had oculocutaneous albinism. These children were divided in two training groups matched on age and diagnosis: a crowded training group (n = 18) and an uncrowded training group (n = 18). Training occurred two times per week during 5 weeks (3500 trials per training). Eleven age - matched children with normal vision were included to assess baseline differences in task performance and test-retest learning. Main outcome measures were task - specific performance, distance and near visual acuity (DVA and NVA), intensity and extent of (foveal) crowding at 5 m and 40 cm, and stereopsis. Training resulted in task - specific improvements. Both training groups also showed uncrowded and crowded DVA improvements (0.10 ± 0.02 and 0.11 ± 0.02 logMAR) and improved stereopsis (670 ± 249″). Crowded NVA improved only in the crowded training group (0.15 ± 0.02 logMAR), which was also the only group showing a reduction in near crowding intensity (0.08 ± 0.03 logMAR). Effects were not due to test-retest learning. Perceptual learning with or without distractors reduces the extent of crowding and improves visual acuity in children with IN. Training with distractors improves near vision more than training with single optotypes. Perceptual learning also transfers to DVA and NVA under uncrowded and crowded conditions and even stereopsis. Learning curves indicated that improvements may be larger after longer training.
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Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study Developmental dyslexia is a language - based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here, we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n = 29) and without (FHD-, n = 21) a family history of developmental dyslexia. We further controlled for socioeconomic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior / middle frontal and right fusiform gyri in FHD- compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD- children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models.
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Laparascopic Splenectomy Due to Splenic Injury after Colonoscopy Colonoscopy, which is routinely performed in diagnosis and treatment of colorectal disorders, is a reliable procedure. Its most frequent complications are bleeding and perforation. Splenic rupture is a very rarely met complication of colonoscopy, and delay in its diagnosis leads to increased morbidity and mortality. We presented a 69 years old female patient, who was diagnosed by computerized abdominal tomography, performed for her abdominal pain, which started following the colonoscopy. After 15 days of medical treatment and follow-up, laparoscopic splenectomy was performed one month after her colonoscopy. The patient was discharged on her 4(th) postoperative day, with uneventful recovery. In patients who have complaint of abdominal pain following colonoscopy, an intraabdominal pathological condition should be considered and computerized abdominal tomography should be performed. If there is no detected intraperitoneal bleeding, in other words, if there is a sub-capsular hematoma of the spleen, medical management by monitoring the vital signs may be preferred. Then, splenectomy should be performed at an appropriate time.
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NAPS - MS: Natalizumab Effects on Parameters of Sleep in Patients with Multiple Sclerosis Patients with multiple sclerosis (MS) have higher rates of fatigue, mood disturbance, and cognitive impairments than healthy populations. Disease -modifying agents may affect sleep. Although patients taking natalizumab often show improvement in fatigue during the first year of therapy, the mechanism behind this effect is unknown. The aim of the NAPS - MS study was to investigate whether natalizumab affected objective measures of sleep as determined by polysomnography (PSG) and multiple sleep latency testing (MSLT) in patients with MS with fatigue or sleepiness initiating therapy. Additional goals were to evaluate changes in measures of fatigue, mood, and cognition and to correlate these measures with objective sleep measures. Patients underwent PSG and MSLT before their first natalizumab infusion and after their seventh. Patients completed the Modified Fatigue Impact Scale, Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and visual analogue scale for fatigue (VAS-F) at their first, fourth, and seventh natalizumab infusions. NeuroTrax cognitive tests and the Hospital Anxiety and Depression Scale (HADS) were performed at the first and seventh natalizumab infusions. Changes in sleep efficiency, wakefulness after sleep onset, and multiple sleep latency from baseline to 6 months of therapy did not reach significance. The FSS, VAS-F, ESS, and HADS scores were significantly improved after 6 months of therapy; cognitive scores were not significantly improved. Although treatment with natalizumab was associated with improvements in fatigue, sleepiness, and mood, changes in objective measures of sleep were not significant.
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Effectiveness of the Consecutive Alternating Administration Course of a Triple Antiviral Combination in Coxsackievirus B3 Infections in Mice Anti-enteroviral chemotherapeutics for clinical use are not registered so far, mainly due to the rapid development of drug-resistance. One of the possible approaches to overcome this problem is the use of combined chemotherapy. However, its application consisting of simultaneously given drugs, is not efficacious because of the development of multiple resistance. Here we present a novel approach for combined application of anti-enteroviral compounds, consisting of a consecutive alternating administration (CAA) course. CAA was tested on 2 in vivo models of Coxsackievirus B3 infection in newborn mice at inoculation dose of 20 MLD50 (50% mouse lethal dose): neurotropic (Nancy strain) and cardiotropic (Woodruff strain) infections. Compounds partnering in a triple combination were selected as enterovirus (EV) replication inhibitors with different mode of action - disoxaril (a VP1 blocker), guanidine.HCl (targeting 2C protein) and oxoglaucine (attacking 3A coding region). The application of this combination by CAA course resulted in around 40 and 60% survival rate in mice infected with Nancy and Woodruff virus, respectively, accompanied by a marked lengthening of the mean survival time (MST). The results obtained are proofs for the prospect of the treatment course by a triple combination through the CAA scheme as an approach interfering the occurrence of drug resistance at EV infections.
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Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety Systemic activation of cannabinoid receptors often induces biphasic effects on emotional memory and anxiety depending on the levels of emotional arousal associated to the experimental context. The basolateral nucleus of the amygdala (BLA) represents a crucial structure for the ability of endocannabinoid (eCB) signaling to modulate emotional behaviour, and receives dense projections from brainstem arousal system nuclei. We examined whether changes in emotional arousal state would influence the ability of acute eCB manipulations within the BLA to modulate anxiety. Rats were tested in an elevated plus maze (EPM) under low or high arousal conditions. The low emotional arousal group was extensively handled and habituated to the experimental room and tested under red light condition, the high emotional arousal group was not handled or habituated and tested under high light condition. We examined amygdalar eCB anandamide (AEA) and 2-arachidonoylglycerol (2-AG) levels immediately after the EPM and the effects of intra- BLA administration of the AEA hydrolysis inhibitor URB597 or the 2-AG hydrolysis inhibitor KML29 on anxiety behaviour. The modulation of anxiety -like behaviour by eCB s in the BLA was strictly dependent on the environmental -associated emotional arousal. Pharmacologically - induced elevations of AEA or 2-AG in the BLA decreased anxiety under conditions of low emotional arousal. Conversely, when the level of emotional arousal increased, local eCB manipulation was ineffective in the modulation of the emotional arousal - induced anxiety response. These findings suggest that, depending on the emotional arousal state, eCB system is differentially activated to regulate the anxiety response in the amygdala and help to understand the state-dependency of many interventions on anxiety.
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Initial stabilisation of preterm infants: a new resuscitation system with low imposed work of breathing for use with face mask or nasal prongs T-piece resuscitation systems are pressure unstable and have high imposed work of breathing (iWOB). Pressure stable respiratory support with low iWOB might improve outcome. We have developed a new resuscitation system that can be used with nasal prongs or face mask. The aim of the study was to describe the in vitro performance of the new system and to perform a clinical feasibility trial of initial stabilisation of preterm infants. A mechanical lung model was used to determine iWOB at increasing levels of continuous positive airway pressure (CPAP). The feasibility trial included 36 infants (27-34 weeks of gestation), who were randomised into three groups (T-piece, new system with face mask or new system with prongs). Collected data included problems with usage, safety, time to stable breathing, need for positive pressure ventilation and intubation. In the mechanical lung model, the new system reduced iWOB with 91.5% (mask) and 86.6% (medium prongs) compared with Neopuff (4 cm CPAP, p<0.001). Informed consent was obtained from 45 patients, 39 were randomised and 36 needed support. Randomisation resulted in an imbalance: The group of new system infants had lower gestational age compared with the T-piece group. Thirteen patients needed positive pressure ventilation (median 20 cm H2O). One infant was intubated. The study did not reveal problems with the equipment or safety. Compared with T-piece systems, the new system had a marked reduction in iWOB in bench tests. The feasibility trial did not reveal problems with usability or safety.
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Hydrogen -rich water regulates effects of ROS balance on morphology, growth and secondary metabolism via glutathione peroxidase in Ganoderma lucidum Ganoderma lucidum is one of the most important medicinal fungi, but the lack of basic study on the fungus has hindered the further development of its value. To investigate the roles of the redox system in G. lucidum, acetic acid (HAc) was applied as a reactive oxygen species (ROS) stress inducer, and hydrogen -rich water (HRW) was used to relieve the ROS stress in this study. Our results demonstrate that the treatment of 5% HRW significantly decreased the ROS content, maintained biomass and polar growth morphology of mycelium, and decreased secondary metabolism under HAc - induced oxidative stress. Furthermore, the roles of HRW were largely dependent on restoring the glutathione system under HAc stress in G. lucidum. To provide further evidence, we used two glutathione peroxidase (GPX)- defective strains, the gpxi strain, the mercaptosuccinic acid (MS, a GPX inhibitor)-treated wide-type (WT) strain, and gpx overexpression strains for further research. The results show that HRW was unable to relieve the HAc - induced ROS overproduction, decreased biomass, mycelium morphology change and increased secondary metabolism biosynthesis in the absence of GPX function. The gpx overexpression strains exhibited resistance to HAc - induced oxidative stress. Thus, we propose that HRW regulates morphology, growth and secondary metabolism via glutathione peroxidase under HAc stress in the fungus G. lucidum. Furthermore, our research also provides a method to study the ROS system in other fungi.
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Activation of the Na(+)/H(+) exchanger in isolated cardiomyocytes through β-Raf dependent pathways. Role of Thr(653) of the cytosolic tail The mammalian Na(+)/H(+) exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes. A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain. In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy. We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf. Endothelin stimulated NHE1 activity and activated Erk-dependent pathways. Inhibition of β-Raf reduced NHE1 activity and Erk-pathway activation. We demonstrated that myocardial β-Raf binds to the C-terminal 182 amino acids of the NHE1 protein and that β-Raf is associated with NHE1 in intact cardiomyocytes. NHE1 was phosphorylated in vivo and the protein kinase inhibitor sorafenib reduced NHE1 phosphorylation levels. Immunoprecipitates of β-Raf from cardiomyocytes phosphorylated the C-terminal 182 amino acids of NHE1 and mass spectrometry analysis showed that amino acid Thr(653) was phosphorylated. Mutation of this amino acid to Ala resulted in defective activity while mutation to Asp restored the activity. The results demonstrate that Thr(653) is an important regulator y amino acid of NHE1 that is activated through β-Raf dependent pathways by phosphorylation either directly or indirectly by β-Raf, and this affects NHE1 activity.
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The Latin American Biological Dosimetry Network (LBDNet) Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included.
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[ "Delayed", "Axillary", "Artery", "Occlusion", "after", "Reverse", "Total", "Shoulder", "Arthroplasty", "Axillary", "artery", "injury", "has", "been", "associated", "with", "shoulder", "dislocation", "and", "surgery", ".", "We", "describe", "a", "case", "of", "delayed", "axillary", "artery", "occlusion", "after", "reverse", "total", "shoulder", "arthroplasty", ".", "The", "injury", "was", "confirmed", "by", "Doppler", "and", "angiography", "and", "was", "treated", "with", "angioplasty", "and", "stenting", ".", "Early", "recognition", "and", "treatment", "of", "this", "injury", "are", "mandatory", "for", "patients", "'", "recovery" ]
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Delayed Axillary Artery Occlusion after Reverse Total Shoulder Arthroplasty Axillary artery injury has been associated with shoulder dislocation and surgery. We describe a case of delayed axillary artery occlusion after reverse total shoulder arthroplasty. The injury was confirmed by Doppler and angiography and was treated with angioplasty and stenting. Early recognition and treatment of this injury are mandatory for patients' recovery.
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Options in treating trigeminal neuralgia: Experience with 195 patients For patients with medically unresponsive trigeminal neuralgia (TN), surgical options include microvascular decompression (MVD), radiofrequency rhizotomy (RF), and stereotactic radiosurgery (SRS). In an attempt to identify the risks and benefits and cost inherent with each of the three modalities, we performed a retrospective review of our experience with 195 cases of TN treated over the past 15 years. Since 2001, 195 patients with previously untreated TN were managed: with MVD in 79, RF in 36, and SRS in 80. All patients reported herein underwent preoperative MRI. Women outnumbered men 122/73 (p=0.045). Follow-up after surgery was 32±46 months. The patients qualifying for MVD were generally healthier and younger, with a mean age ± SD of 57±14, compared to those undergoing RF (75±15) or SRS (73±13, p<0.0001). In case of relapse, medical treatment was always tried and failed prior to consideration of surgical intervention. A second surgical procedure was necessary in 2, 23, and 18 patients initially treated with MVD, RF, and SRS respectively (p<0.0001). In the patients treated with MVD, RF, and SRS, the average number of procedures per patient necessary to achieve pain control was 1.1, 2.0, and 1.3 respectively (p=0.001). There were 7 complications in the patients treated with MVD but no deaths. Numbness was present in 13, 18, and 29 patients treated with MVD, RF, and SRS respectively (p=0.008). MVD for TN is the treatment least likely to fail or require additional treatment. Patients who underwent MVD were younger than those undergoing RF or SRS. The highest rate of recurrence of TN was encountered in patients undergoing RF (64%). Facial numbness was least likely to occur with MVD (16%) compared to RF and SRS (50% and 36% respectively).