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CDK4: A manuscript Restorative Targeted regarding Extramammary Paget's Condition.
Introduction Fetal growth restriction (FGR), viz., birth weight less then 10th percentile is a common pregnancy complication which increases the risk of adverse fetal and newborn outcomes. The placenta is the key organ for fetal growth as it controls oxygen and nutrient availability. This study aims to elucidate the mechanisms of and identify putative placental biomarkers for FGR using high-resolution metabolomics.Methods Placenta samples from 19 FGR cases and 30 controls were analyzed using proton magnetic resonance (1H NMR) spectroscopy and direct flow injection mass spectrometry with reverse-phase liquid-chromatography mass spectrometry (DI-LC-MS/MS). Significant concentration differences (p-value less then .05) in 179 of the 220 metabolites were measured.Results Of the 179 metabolites, 176 (98.3%) had reduced placental levels in FGR cases. The best performing metabolite model 3-hydroxybutyrate, glycine and PCaaC420 achieved an AUC (95% CI) = 0.912 (0.814-1.000) with a sensitivity of 86.7% and specificity of 84.2% for FGR detection. Metabolite set enrichment analysis (MSEA) revealed significant (p  less then  .05) perturbation of multiple placental metabolite pathways including urea metabolism, ammonia recycling, porphyrin metabolism, bile acid biosynthesis, galactose metabolism and perturbed protein biosynthesis.Conclusion The placental metabolic pathway analysis revealed abnormalities that are consistent with fetal hepatic dysfunction in FGR. Near global reduction of metabolite concentrations was found in the placenta from FGR cases and metabolites demonstrated excellent diagnostic accuracy for FGR detection.Aim Roles of forced running exercise (FE) in remediation of neurogenesis inhibition and radiation-induced cognitive dysfunction were investigated in a whole-brain irradiation mice model via the regulation of DNA 5-hydroxymethylation modification (5 hmC) and its catalytic enzymes ten-eleven translocation (Tet) proteins. Materials & methods Hippocampal neurogenesis and cognitive function, DNA 5 hmC level and Tet expression were determined in mice. Results The expression of DNA 5 hmC and Tet2, brain-derived neurotrophic factor significantly decreased in hippocampus postradiation. FE mitigated radiation-induced neurogenesis deficits and cognitive dysfunction. Furthermore, FE increased 5 hmC and brain-derived neurotrophic factor expression. SC1, a Tet inhibitor, reversed partly such changes. Conclusion Tet-mediated 5 hmC modification represents a kind of diagnostic biomarkers of radiation-induced cognitive dysfunction. Targeting Tet-related epigenetic modification may be a novel therapeutic strategy for radiation-induced brain injury.OBJECTIVE In patients with velocardiofacial syndrome (VCFS), medial displacement of the internal carotid arteries (ICAs) may increase the risk of vascular injury during the surgical correction of velopharyngeal dysfunction (VPD). Some surgeons advocate the use of vascular imaging studies prior to surgery. Nevertheless, the role of preoperative imaging is still controversial. This study aimed to review the current practice of the UK cleft units and also examine our own practice at the Evelina London Children's Hospital in relation to children with VCFS undergoing speech surgery over the previous 7 years. DESIGN A questionnaire was sent to all UK cleft surgeons to enquire about the management and use of preoperative vascular imaging in patients with VPD and VCFS. A retrospective study was also conducted of the unit's 7-year series of patients with VPD and VCFS. RESULTS Thirty-four completed questionnaires were returned (response rate 100%). Most UK surgeons (73.5%) do not regularly order preoperative vascular imaging for patients with VCFS although some reportedly would consider it if a posterior pharyngeal wall pulsation was visible. In our unit, between 2013 and 2019, a total of 40 patients affected by VCFS have been assessed for VPD. A magnetic resonance angiography (MRA) was performed for 23 patients. Medial deviation of the ICAs was identified in 7 (30%) patients. CONCLUSIONS The results of the national survey showed no consensus on routine use of preoperative vascular imaging. Our retrospective study showed a 30% prevalence of medialized ICAs in our patient cohort. In these patients, the MRA findings influenced the choice of speech surgery.Needle biopsy is a well-established component in the evaluation of thyroid nodules. The biopsy is usually performed with an ultrasound guidance and consists of either fine-needle aspiration or core needle biopsy. Although these terms are often used interchangeably, their difference is important. To our knowledge, we discuss the first reported case of biopsy-proven laryngeal nerve injury and permanent vocal fold paralysis following ultrasound-guided core biopsy of the thyroid. We advocate this complication be discussed as part of the consent process.Laryngeal squamous cell carcinoma (LSCC) is one of the most common laryngeal tumors, and its incidence is increasing yearly; however, whether lymph node dissection should be performed during surgery remains unclear. We retrospectively analyzed the clinical and pathological data of 246 cases of LSCC and developed a nomogram for the prediction of lymph node metastasis (LNM) of LSCC. The predictive performance and consistency of the model were evaluated using the consistency coefficient (C-index) and calibration curve, respectively. Among 246 cases of LSCC, 52 cases had metastasis with a positivity rate of 21.14%. Multivariate analyses showed that dysphagia, clinical T stage, and pathological differentiation were independent risk factors for LNM in LSCC. The accuracy of the contour map used to predict the risk for LNM was 0.809. Overall, this nomogram model can be used to evaluate LNM in patients with LSCC before surgery to decide whether to conduct neck dissection and improve patient prognosis.Significance Bioactive sulfur species such as hydrogen sulfide (H2S), persulfide species (R-SnSH, n ≥ 1), hydrogen polysulfide (H2Sn, n ≥ 2), sulfur dioxide (SO2), and carbon disulfide (CS2) participate in various physiological and/or pathological pathways such as vasodilation, apoptosis, inflammation, and energy metabolism regulation. The oxidation state of the individual sulfur species endows them unique biological activities. Recent Advances There have been great strides made in achieving molecular understanding of the sulfur-signaling processes. Critical Issues The development of various chemical tools that deliver reactive sulfur species in a controllable manner has played an important role in understanding the different roles of various sulfur species. In this review, we focus on three types of sulfur species, including persulfide, SO2, and CS2. Starting with a brief introduction of their physiological functions, we will then assess the various drug delivery strategies to generate persulfide species, SO2, and CS2 as research tools and potentially as therapeutic agents. Future Directions Development of donors of various sulfur species that respond to distinct stimulus is critical for this field. Another key to the long-term success of this field is the identification of an area of unmet medical need that can be addressed with these sulfur species.OBJECTIVES (1) To assess the evolution of prepalatoplasty sleep oximetry (PRESO) and postpalatoplasty sleep oximetry (POSSO) in cleft patients and (2) to evaluate the impact of the size of the nasopharynx on PRESO and POSSO values. STUDY DESIGN Retrospective cohort study. PATIENTS AND METHODS In 81 patients with cleft palate and/or cleft lip, the following data were prospectively collected patient demographics and prepalatoplasty cleft palate measurements. All the patients had at least 1 PRESO and POSSO. A Kaplan-Meier curve was obtained from all the sleep oximetry results. Transverse nasopharyngeal area (TNA) pre- and postvalues were compared for each group with paired t tests, while analysis of variance was used to compare TNA pre- and postscores between the groups with a Bonferroni correction for multiple comparisons. RESULTS POSSO results were normal or showed mild desaturations in most patients in the few weeks following palatoplasty. For the cohort, no statistically significant changes were found between PRESO and POSSO values. A 2-fold variation in the area of the TNA was found before palatoplasty within identical cleft malformation cases. No statistically significant association was found between the TNA or the a/30 - b 1 parameter values and the sleep study scores. CONCLUSIONS The patients with the smaller nasopharyngeal areas presented identical PRESO and POSSO results when compared to those with larger nasopharyngeal sizes. Future studies should address the possible association between prepalatoplasty and postpalatoplasty TNAs and the occurrence of velopharyngeal deficiency later in life.Antimicrobial properties of solid copper (Cu) surfaces against various microorganisms have been demonstrated, but little is known about the durability and relative antimicrobial efficacy of different Cu formulations currently used in healthcare. The aim of this study was to assess whether three different formulations of copper-bearing alloys (integral, spray-on and Cu-impregnated surfaces) and a stainless steel control differed in their antimicrobial efficacy, durability, and compatibility with hospital-grade cleaner/disinfectants. The U.S. Environmental Protection Agency draft protocol for the evaluation of bactericidal activity of Cu containing alloys was modified to more accurately reflect cleaning methods in healthcare. The three different Cu alloys were evaluated using 25 × 25 × 3 mm disks subjected to one year of simulated cleaning and disinfection using the Wiperator™ with microfiber cloths presoaked in three common hospital disinfectants accelerated hydrogen peroxide, quaternary ammonium, or sodium hypochlorite solutions. Bactericidal activity was evaluated using Staphylococcus aureus and Pseudomonas aeruginosa. While all Cu formulations exhibited some antimicrobial activity, integral and spray-on Cu alloys showed the greatest efficacy. Assessments of durability included documentation of changes in mass, morphological changes by scanning electron microscopy, chemical composition alteration by energy-dispersive x-ray spectroscopy, and surface roughness alteration using profilometry over one year of simulated use. The integral Cu alloy had the least mass loss (0.20% and 0.19%) and abrasion-corrosion rate (6.28 and 6.09 μm/yr) compared to stainless steel. The integral product also showed the highest durability. Exposure to disinfectants affected both the antimicrobial efficacy and durability of the various copper products.Nanostructured composite thin films showing magnetic exchange coupling at the material interface have attracted great interest for the development of electronic components such as spin-valves. Besides the commonly performed fabrication of multilayer systems, the utilization of nanoparticle building blocks holds great potential for thin films with tailored magnetic properties and allows the facile but controlled combination of materials with complementary magnetic characteristics. In this work, we present the use of prefabricated highly crystalline iron platinum (fcc-FePt) and iron oxide (FexOy) nanoparticles for the preparation of nanocomposite thin films with varying compositions by wet processing from mixed dispersions. The resulting multiphase coatings showed high homogeneity, low surface roughness, and superparamagnetic behavior. By the variation of the amount of incorporated iron oxide, a precise adjustment of the magnetization at high field strength could be achieved. Furthermore, calcination under inert gas atmosphere resulted in a controlled phase transition of the magnetic phases and thus, in purely metallic coatings composed of ferromagnetic fct-FePt and antiferromagnetic fcc-FePt3, a decrease in surface roughness as well as high magnetic coercivity at room temperature.
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