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Primary closure versus delayed or no closure for traumatic wounds due to mammalian bite.Mammalian bites are a common presentation in emergency and primary healthcare facilities across the world. The World Health Organization recommends postponing the suturing of a bite wound but this has not been evaluated through a systematic review.
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Allergic Rhinitis to Weed Pollen in Germany: Dominance by Plantain, Rising Prevalence, and Polysensitization Rates over 20 Years.In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy.
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Dietary Intervention: An Essential Part of the Management of Patients Affected by Hidradenitis Suppurativa.
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Fork pausing complex engages topoisomerases at the replisome.Replication forks temporarily or terminally pause at hundreds of hard-to-replicate regions around the genome. A conserved pair of budding yeast replisome components Tof1-Csm3 (fission yeast Swi1-Swi3 and human TIMELESS-TIPIN) act as a "molecular brake" and promote fork slowdown at proteinaceous replication fork barriers (RFBs), while the accessory helicase Rrm3 assists the replisome in removing protein obstacles. Here we show that the Tof1-Csm3 complex promotes fork pausing independently of Rrm3 helicase by recruiting topoisomerase I (Top1) to the replisome. Topoisomerase II (Top2) partially compensates for the pausing decrease in cells when Top1 is lost from the replisome. The C terminus of Tof1 is specifically required for Top1 recruitment to the replisome and fork pausing but not for DNA replication checkpoint (DRC) activation. We propose that forks pause at proteinaceous RFBs through a "sTOP" mechanism ("slowing down with topoisomerases I-II"), which we show also contributes to protecting cells from topoisomerase-blocking agents.
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A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes.The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is important. Here, we describe a single mechanism incorporating features of both models. We show that termination is completely abolished by rapid elimination of CPSF73, which causes very extensive transcriptional readthrough genome-wide. This is because CPSF73 functions upstream of modifications to the elongation complex and provides an entry site for the XRN2 torpedo. Rapid depletion of XRN2 enriches these events that we show are underpinned by protein phosphatase 1 (PP1) activity, the inhibition of which extends readthrough in the absence of XRN2. Our results suggest a combined allosteric/torpedo mechanism, in which PP1-dependent slowing down of polymerases over termination regions facilitates their pursuit/capture by XRN2 following PAS processing.
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Differences in obsessive-compulsive symptom dimensions between patients with epilepsy with obsessive-compulsive symptoms and patients with OCD.Clinical correlates of obsessive-compulsive symptoms (OCS) were evaluated in 100 adult consecutive outpatients with epilepsy, using the Obsessive-Compulsive Inventory (OCI-R), Beck Depression Inventory (BDI), Dissociative Experiences Scale (DES-II), and the Schizotypal Personality Questionnaire (SPQ). Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) was applied to determine the types and severity of OCS to the 45 patients with epilepsy who were over 21 points on the OCI-R scale and 30 patients who were with diagnosed obsessive-compulsive disorder (OCD) among the patients in the psychiatry outpatient clinic, as a control group. As a result, it was found that patients with epilepsy with OCS tend to have more symmetry/exactness obsessions and compulsions, whereas patients with OCD had significantly more contamination/cleaning and aggressiveness obsessions and compulsions. In addition, OCS was found to be significantly higher in temporal lobe epilepsy (TLE) and extratemporal epilepsy than generalized epilepsy. However, OCS were correlated with depression, dissociation, and schizotypy in patients with epilepsy, while only depression was predictive when regression analysis was performed for OCS. This study is the first study to compare patients with OCD with patients with epilepsy in terms of the nature of OCS and first identified the differences in OCS dimensions between patients with epilepsy with OCS and patients with OCD.
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Exploring non-pharmacological management among anesthesia providers to reduce preoperative distress in children.Preparation for surgery with the induction of general anesthesia is one of the most stressful events that a child can experience. It produces several threats to the child, including physical harm, parent separation, and fear of the unknown. Anesthesia providers utilize non-pharmacological and pharmacological interventions to decrease this preoperatively. However, little is known about the non-pharmacological interventions utilized by anesthesia providers in practice. The purpose of this study was to explore non-pharmacological interventions utilized by anesthesia providers before and during the induction of general anesthesia to reduce preoperative distress in children ages one to six years old. A qualitative descriptive approach was used in this study. Twenty anesthesia providers, fourteen registered nurse anesthetists and six anesthesiologists, participated in face to face, in-depth interviews in South Florida. Content analysis was used to identify and define the major themes that emerged from the interviews. A total of seven main themes were identified. Only the three themes directly related to parent-provider-child relationship are discussed in this paper: (I) Communication, (II) Observational Skills, and (III) Parental Presence. The anesthesia providers who participated in this study offered an opportunity to better understand the non-pharmacological interventions used to impact the management of preoperative distress among children. Study findings provide evidence about non-pharmacological anesthesia providers' clinical work not found elsewhere in the literature. Non-pharmacological interventions are effective in reducing preoperative distress in children.
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Interferon regulatory factor 2 plays a positive role in interferon gamma expression in golden pompano, Trachinotus ovatus (Linnaeus 1758).In fish, interferon (IFN) regulatory factor 2 (IRF2) is a regulator of the type I IFN-dependent immune response, thereby playing a crucial role in innate immunity. However, the specific mechanism by which IRF2 regulates type II IFN in fish remains unclear. In the present study, first, to analyse the potential role of golden pompano (Trachinotus ovatus) IRF2 (ToIRF2) in the immune response, the mRNA level of ToIRF2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) after parasite infection. ToIRF2 was upregulated at early time points in both local infection sites (skin and gill) and system immune tissues (liver, spleen, and head-kidney) after stimulation with Cryptocaryon irritans. Second, to investigate the modulation effect of ToIRF2 on type II IFN (interferon gamma, IFNγ) expression, a promoter analysis was performed using progressive deletion mutations of ToIFNγ. The expression level of IFNγ-5 was highest among the five truncated mutants in response to ToIRF2, indicating that the core promoter region was located from -189 bp to +120 bp, which included the IRF2 binding sites. Mutation analyses showed that the activity of the ToIFNγ promoter dramatically decreased after the targeted mutation of the M1, M2 or M3 binding sites. Additionally, electrophoretic mobile shift assay (EMSA) confirmed that IRF2 interacted with the M1 binding site in the ToIFNγ promoter region to dominate ToIFNγ expression. Finally, overexpressing ToIRF2 in vitro notably increased ToIFNγ and the transcription of several type II IFN/IRF-based signalling pathway genes. These results suggested that ToIRF2 might be involved in the host defence against C. irritans infection and contribute to a better understanding of the transcriptional mechanisms by which ToIRF2 regulates type II IFN in fish.
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Ectonucleotide pyrophosphatase 2 (ENPP2) plays a crucial role in myogenic differentiation through the regulation by WNT/β-Catenin signaling.Ectonucleotide pyrophosphate phosphodiesterase type II (ENPP2), also known as Autotaxin (ATX), is an enzyme present in blood circulation that converts lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA). While LPA has been demonstrated to play diverse roles in skeletal myogenesis, mainly through in vitro studies, the role of ENPP2 in skeletal myogenesis has not been determined. We previously found that Enpp2 is induced by a positive WNT/β-Catenin signaling regulator, R-spondin2 (RSPO2), in C2C12 myoblast cells. As RSPO2 promotes myogenic differentiation via the WNT/β-Catenin signaling pathway, we hypothesized that ENPP2 may act as a key mediator for the crosstalk between WNT and LPA signaling during myogenic differentiation. Herein, we found that ENPP2 function is essential for myogenic differentiation in C2C12 cells. Pharmacological ENPP2 inhibitors or RNAi-mediated Enpp2 gene knockdown severely impaired the myogenic differentiation, including the cell fusion process, whereas administration of the recombinant ENPP2 protein enhanced myogenic differentiation. Consistent with the in vitro results, mice lacking the Enpp2 gene showed a disrupted muscle regeneration after acute muscle injury. The size of newly regenerated myofibers in Enpp2 mutant muscle was significantly reduced compared with wild-type regenerated muscle. Modified expression patterns of myogenic markers in Enpp2 mutant muscle further emphasized the impaired muscle regeneration process. Finally, we convincingly demonstrate that the Enpp2 gene is a direct transcriptional target for WNT/β-Catenin signaling. Functional TCF/LEF1 binding sites within the upstream region of Enpp2 gene were identified by chromatin immunoprecipitation using anti-β-Catenin antibodies and reporter assay. Our study reveals that ENPP2 is regulated by WNT/β-Catenin signaling and plays a key positive role in myogenic differentiation.
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A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells.Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (HO)-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the HO-mediated conversion of boronate to free phenol. The boronate-protected Nap (PNap) can exploit increased levels of HO in HepG2 cells to in situ release Nap followed by its efflux via conjugation with reduced glutathione (GSH), allowing that the Nap-GSH adduct works as a Cu(II) ionophore to induce continuously GSH depletion via a reduction-dependent releasing of Cu(I) by GSH. This strategy endows PNap with the unprecedented ability to hit multi-redox characteristics (increased levels of HO, GSH and copper) of HepG2 cells, leading to ROS generation preferentially in HepG2 cells along with their selective death.
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