BACKGROUND AND PURPOSE: Chemical 2, 4-dinitrofluorobenzene (DNFB), commonly called as Sanger’s reagent, is well known as skin sensitizer to cause dermatitis. However, how the DNFB causes skin inflammation remains unknown. In this study we aimed at identifying the molecular target that DNFB acts on. EXPERIMENTAL APPROACH: We used a fluorescent calcium imaging plate reader as an initial screening assay and patch-clamp recordings for validation. Molecular docking in combination with site-directed mutagenesis was carried out to investigate DNFB binding sites in TRPA1 ion channel. KEY RESULTS: We found the chemical DNFB that selectively activates TRPA1 channel with EC50 of 2.36 ± 0.26 µM. Single-channel recording reveals that DNFB increases the channel open probability and acts on three residues C621, Y658 and E625 critical for DNFB-mediated TRPA1 activation. CONCLUSION AND IMPLICATIONS: Our findings not only explain a molecular mechanism underlying the dermatitis and pruritus caused by chemical DNFB, but also provides a molecular tool that is 7.5-time more potent than current AITC molecule and can be used for elucidating TRPA1 channel pharmacology and pathology.
There is limited data about various effect of COVID-19 in pregnancy. The Covid-19 pandemic can increase anxiety or schizophrenia exacerbation. Neonatal malformations from antipsychotic drugs exposures during first trimester of pregnancy have been reported. However, their effect near delivery have been less studied. Keywords: Covid-19, pregnancy, mental health, neonatal malformations
Objective Histopathologically to determine the relationship between penile elastography ultrasonography and erectile dysfunction. Material and Method 12 patients who applied to our clinic for erectile dysfunction in the last 1 year and accepted this study were included . Preoperative two-dimensional shear wave elastography imaging was performed in 12 patients and recorded in the Pascal (kPa) unit. Approximately 0.5x0.5x0.5 cm tissue samples were taken from the right and left spongy tissue during penile prosthesis implantation operation. Tissue samples were sent to the pathology department. The percentage of the area covered by muscle fibers and elastic fibers in the corpus cavernosum was noted semi-quantitatively (ratio of muscle fibers and cavernous body elastic fiber score). All data obtained were compared with each other. Results Cavernous body elastic fiber score data(Grouped Score 1, 2 and 3) and percentage of cavernous body muscle fibers data (Grouped %10,%20,%30… %100) were compared with Shear wave elastography data (kPa). The results were not statistically significant according to the Kruskal Wallis Test and Spearman’s correlation test. Cavernous body elastic fiber score and the percentage of cavernous body muscle fibers were also compared, it was not statistically significant according to the Kruskal Wallis test and Spearman’s correlation test. The data we obtained as a result of our study showed that penile elastographic imaging is not a reliable method in the diagnosis of erectile dysfunction. Conclusions Penile shear wave elastography can be used clinically to quantitatively assess the amount of smooth muscle cells and elastic fibers in the penis, but it deserves to be studied with a larger number of patients and a more specific interpretation of the pathology preparation. Keywords: Penile elastography, erectile dysfunction, penile prosthesis, shear wave
Objectives As a pivotal part of precision therapy, PD‐1/PD‐L1 immunotherapy has been gradually used in head and neck cancer (HNC). We investigated the effect and adverse events of PD‐1/PD‐L1 inhibitors alone or with conventional therapy. Design The groups using PD-1/PD-L1 immunotherapy or combining with conventional therapy were defined as the experimental groups, while the standard of care were the control groups. Cochrane Library, Embase, PubMed, and Web of Science were undertaken to identify literature up to November 20, 2020. Overall survival (OS) and progression-free survival (PFS) were the primary outcome measures. Secondary outcome measures included objective response rate (ORR), disease control rate (DCR), any grade and grade≥3 adverse events (AE). Results Five randomized controlled trials (RCTs) and nine single-arm trials were included in the systematic review. The OS of the experimental groups was better than the control groups (OR = 0.63, 95%CI: 0.49‐0.82, I²=35%, P=0.0004), particularly in patients who smoke current/former or with human papillomavirus negative (HPV-). The experimental groups had longer OS than the control groups in patients with PD-L1 positive (OR = 0.75, 95% CI: 0.65‐0.85, I²=0%, P<0.0001). Patients with HPV positive (HPV+) had more favorable OS than those with HPV- (OR = 0.56, 95%CI:0.44-0.71, I²=39%, P<0.00001). There were statistical differences in AEs (e.g., fatigue, rash, hypothyroidism, etc.) and no statistical differences in PFS, ORR, and DCR. Conclusion PD-1/PD-L1 immunotherapy or combining with conventional therapy can improve the treatment effect and induce fewer adverse events of digestion and blood system, except for hypothyroidism.
Plant carbon transport is controlled by a multitude of parameters both internal and external to the sugar transporting phloem tissue. Sucrose transporter kinetics, conduit hydraulic resistance, and xylem water stress are all hypothesized to impact the amount of carbon delivered to sink tissues. However, the most important traits determining carbon export under drought are not well understood, especially for species with active molecular regulation of sucrose transport. This in turn limits our ability to assess species' resistances to phloem dysfunction under drought. Here, we use an integrated xylem-phloem-stomatal model to calculate leaf water potential from soil dryness, which is then used to determine gas exchange and phloem pressure gradients. We quantitatively compare the impacts of phloem loading kinetics, including feedbacks between loading and phloem pressure, phloem conduit resistances, and stomatal responses to water stress, on the total carbon export to sinks during drought. Regulating sucrose transporter kinetics which downregulates loading at high phloem pressures prevented runaway viscosity in the phloem sap and was the most important determinant of export rates under drought. In contrast to previous models, we found this feedback mechanism decoupled stomatal traits from phloem export efficiency during drought and increased the operational range of phloem hydraulic resistances.
Objective: This study was conducted to determine healthcare professionals’ fear of COVID-19 in and their attitudes towards being vaccinated against COVID-19. Method: The sample of this descriptive study was composed of 302 healthcare professionals working in a university research and training hospital. The data were collected with the help of an online survey method created with the help of Google Forms using the “Form for Determining Healthcare Professionals’ Attitudes towards Being Vaccinated” and “The Fear of COVID-19 Scale” between December 28, 2020 and January 13, 2021. Results: The mean total Fear of COVID-19 Scale score of the healthcare professionals participating in the study was found to be 17.20 ± 6.015. A significant relationship was found between the Fear of COVID-19 Scale total score and participating healthcare professionals’ gender, status of education, status of flu vaccination and status of being diagnosed with COVID-19 (p <0.005). Conclusion: According to research results, it was found that healthcare professionals experienced moderate fear, almost half of them were undecided about the COVID-19 vaccine, their thoughts about vaccination were positive and they were mostly concerned about the side effects of the vaccine.
Situs inversus totalis associated with partial anomalous pulmonary venous connection is a very rare congenital heart malformation. Herein, we describe successful surgical repair of the case of a 30-month-old girl who had situs inversus totalis, partial anomalous pulmonary venous connection , large atrial septal defect, and severe pulmonary hypertension.
Objectives: The aim of this study has been to analyze effects on Quality of Life (QoL) of the multilevel surgery for Obstructive Sleep Apnea (OSA). Also, we have compared the impact on QoL of two different treatments for patients with moderate to severe OSA such as CPAP and transoral robotic surgery (TORS). Design: 67 OSA patients who underwent multilevel robotic surgery and 67 OSA patients treated with CPAP were enrolled in a Group 1 and Group 2 respectively. The Glasgow Benefit Inventory (GBI) questionnaire has been administrated to all patients to evaluate the changes in the QoL after the different OSA treatment. Respiratory outcomes pre and post treatment were evaluated and compared. Results: Group 1 showed a GBI total average value of +30.4, whereas the group 2 a value of +33.2 . No statistical difference emerged (p=0.4). General benefit score showed no difference between groups (p = 0.1). Better values of social status benefit (p= 0.0006) emerged in CPAP Group, whereas greater physical status benefit (p=0.04) was showed in TORS Group. Delta-AHI (-23.7 ± 14.3 vs -31.7 ± 15.6; p = 0.001), Delta-ODI (-24.5 ± 9.5 vs. -29.4 ±10.5; p = 0.001) showed better values in CPAP group. Therapeutic success rate of Multilevel TORS Group was 73.1% and 91% in CPAP group (p = 0.01) respectively. Conclusion: Multilevel TORS and CPAP have a positive effect in quality of life of OSA patients. Greater social support has been reported in CPAP group and better physical health status in TORS group.
Bacteriophage is considered an alternative to antibiotics and environmentally friendly approach to tackle antimicrobial resistance (AMR) in aquaculture. Here, we reported isolation, morphology and genomic characterizations of a newly isolated lytic bacteriophage, designated pAh6.2TG. Host range and stability of pAh6.2TG in different environmental conditions, and protective efficacy against a pathogenic multidrug-resistant (MDR) Aeromonas hydrophila in Nile tilapia were subsequently evaluated. The results showed that pAh6.2TG is a member of the family Myoviridae which has genome size of 51,780 bp, encoding 65 putative open reading frames (ORFs), and is most closely related to Aeromonas phage PVN02 (99.33% nucleotide identity). The pAh6.2TG was highly specific to A. hydrophila and infected 83.3% tested strains of MDR A. hydrophila (10 out of 12) with relative stability at pH 7 9, temperature 0 40 °C and salinity 0 40 ppt. In experimental challenge, pAh6.2TG treatments significantly improved survivability of Nile tilapia exposed to a lethal dose of the pathogenic MDR A. hydrophila, with relative percent survival (RPS) of 73.3% and 50% for phage multiplicity of infection (MOI) 1.0 and 0.1, respectively. Significant reduction of bacterial counts in rearing water at 3 h (6.7 ± 0.5 to 18.1 ± 6.98 folds) and in fish liver at 48 h post-treatment (2.7 ± 0.24 to 34.08 ± 26.4 folds) was observed in phage treatment groups while opposite pattern for bacterial counts was observed in untreated control. Interestingly, the surviving fish provoked specific antibody (IgM) against the challenged A. hydrophila. These results might explain the higher survival in phage treatment groups. In summary, the findings suggested that the lytic bacteriophage pAh6.2TG is an effective alternative to antibiotics to control MDR A. hydrophila in tilapia and possibly other freshwater fish.
The paper deals with the stability problem of neural networks with discrete and leakage interval time-varying delays. Firstly, a novel Lyapunov-Krasovskii functional was constructed based on the neural networks leakage time-varying delay systems model. The delayed decomposition approach (DDA) and integral inequality techniques (IIA) were altogether employed, which can help to estimate the derivative of Lyapunov-Krasovskii functional and effectively extend the application area of the results. Secondly, by taking the lower and upper bounds of time-delays and their derivatives, a criterion on asymptotical was presented in terms of linear matrix inequality (LMI), which can be easily checked by resorting to LMI in Matlab Toolbox. Thirdly, the resulting criteria can be applied for the case when the delay derivative is lower and upper bounded, when the lower bound is unknown, and when no restrictions are cast upon the derivative characteristics. Finally, through numerical examples, the criteria will be compared with relative ones. The smaller delay upper bound was obtained by the criteria, which demonstrates that our stability criterion can reduce the conservatism more efficiently than those earlier ones.
In this study, a chemically defined, animal component-free media was developed to promote Vero growth in suspension. Key media compounds were screened using Plackett-Burman styled experiments to create a media formulation to support suspension growth. Vero cells remained viable in suspension, but their growth rate was extremely low, conversely, other cell types such as CHO-K1, MDCK and HEK293T were able to grow in single cell suspension in the same media. To investigate the slow growth of Vero cells, RNA-Seq analysis was conducted. Vero cells were cultured in three different conditions: adherently in serum-containing medium, adherently in in-house medium, and in suspension in low calcium and magnesium in-house medium. This study illustrates that adherent cells maintain similar gene expression, while the suspension phenotype tends to overexpress genes related to renal tubules.
In this paper, a rapid and high accurate numerical method for pricing discrete single and double barrier knock-out call options is presented. With regard to the well-known Black-Scholes model, the price of an option in each monitoring date could be calculated by computing a recursive integral formula that is based on the heat equation solution. We have approximated these recursive solutions with the aid of Lagrange interpolation on Jacobi polynomial nodes. After that, an operational matrix, that makes our computation significantly fast, has been derived. In some theorems, the convergence of the presented method has been shown and the rate of convergence has been derived. The most important benefit of this method is that its complexity is very low and does not depend on the number of monitoring dates. The numerical results confirm the accuracy and efficiency of the presented numerical algorithm.
Retained Products of Conception as an Etiology for EndometritisPietro Bortoletto, MD1, Phillip A. Romanski, MD1, Nina Schatz-Siemers, DO2, Steven D. Spandorfer, MD11 The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, 1305 York Ave, 7th Floor, New York, NY 10021, USA.2 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY 10021, USA.
Background: Postoperative atrial fibrillation (POAF) occurs in 20% to 50% of patients soon after cardiac surgery, and is associated with subsequent newly developed AF. Left atrial appendage closure is effective in preventing stroke among patients with nonvalvular AF. However, the prophylactic effect of left atrial appendage amputation (LAAA) in stroke prevention among patients with sinus rhythm has not been proven. Methods: We analyzed 977 consecutive patients undergoing off-pump coronary artery bypass grafting (OPCAB) with sinus rhythm, with or without concomitant LAAA, from 2011 to 2017 at our institution in a retrospective observational manner. A total of 550 patients (56.3%) underwent concomitant LAAA, any effect thereof in preventing early (<30 days) and later stroke was examined. Results: The incidences of POAF and early stroke were not significantly different between the groups. The incidence of later stroke was higher in patients without LAAA than in those with LAAA (4.0% vs. 1.6%; p = 0.02). In a subanalysis of patients without LAAA, stroke occurred more frequently in those with POAF than those without POAF (7.5% vs. 2.7%; p = 0.03), while in patients receiving LAAA, stroke incidences did not differ between those with and without POAF. Multivariate cox proportional hazard model showed POAF without LAAA was the only independent predictor of stroke (HR: 2.86; 95% CI: 1.10 to 7.45; p=0.03). Conclusions: Concomitant surgical LAA amputation during OPCAB reduces the risk of stroke.
Objective: This study aims to investigate the mortality factors in hemodialysis patients and kidney transplant patients with COVID-19 patients. Method: The demographic, clinic, laboratory, and radiologic signs of the kidney transplant and hemodialysis patients diagnosed with COVID-19 between 11 March 2020-11 March 2021 were evaluated. Results: To this study, 72 hemodialysis (median age, 57.5 Q1-Q3:43-65; female:36/50%) and 58 kidney transplant (median age, 44.5 Q1-Q3:28.75-55.25; female:21/36.2%) were included. Fifteen HD patients (20.8%) died. To identify the independent predictors of in-hospital mortality, multivariable logistic regression analyses were performed using the variables in the univariate analyses including age, female gender, diabetes mellitus, ferritin, d-dimer, albumin, CRP, procalcitonin, dyspnea. Age (OR:1.12, 95% [CI]: 1.03-1.21, p=0.004), and dyspnea (OR: 9,7 95% CI 1.80-52.2, p=0.008) were found to be associated with in-hospital mortality. Nine (15.5%) of transplant patients died. The median time from the beginning of symptoms to the time of admission was 3 days (2-5). And this rate was 2 (2-3) and 5 (4-5.75) days, respectively, for patients followed up in our center and the external centers (p<0.001). Although an increase in CRP, ferritin, D-dimer levels, dyspnea, and bilateral involvement in CT images was statistically significant in the univariate analysis, no single factor was found to be related to mortality in multivariate analysis. Conclusion: Both HD and renal transplant patients should be followed closely. Early admission of HD and RT patients might be life-saving when suspected. Early inclusion of these patients into the vaccination program might reduce mortality. However, large-scale prospective randomized studies are needed.
Aims: To evaluate the effect of silver nanoparticle, itraconazole and a combination of the two agents on the adherence of Candia albicans, Streptococcus mutans and Enterococcus faecalis on acrylic and silicone tissue conditioners. Materials and Methods: 40 pellets of Group 1 ( GC Soft Liner) and 40 of Group 2 (Sofreliner) were fabricated. The pellets were immersed in a solution of silver nanoparticles or itraconazole or a 1:1 ratio of the combination of the two medicaments. The amount of biofilm formed was assessed by the ELISA reader. Results: A decrease in adherence of Candida albicans was seen in acrylic and silicone-based tissue conditioners when compared to the untreated control samples. Silicone based tissue conditioner showed the least adherence of Candida albicans when treated with 1:1 ratio of silver nanoparticles and itraconazole. There was a statistically significant difference in microbial adhesion between acrylic and silicone tissue conditioner (p<0.001).Pellets treated with silver nanoparticles were studied for adherence of Streptococcus mutans , Candida albicans and Enterococcus faecalis. A statistically significant decrease in all three microbial adherences was observed with this group. (p<0.001) Conclusion: Silver nanoparticles and itraconazole are effective antifungal and antibacterial agents that can potentially decrease microbial colonization of Candia albicans , Streptococcus mutans and Enterococcus faecalis on tissue conditioners. Clinical implications: Silver nanoparticles and itraconazole when used will decrease biofilm formation that will not only improve the overall health of the oral cavity but also prevent denture stomatitis and diseases associated with poor oral hygiene protocols. Keywords: Silver nanoparticles, tissue conditioners, itraconazole, antimicrobial.
Background: Stroke is one of the leading causes of repetitive and disability, affecting the quality of life of the patients negatively, causing depressive symptoms. Aim: The aim of this study was to determine the clinical pharmacist’s contribution on treatment adherence and quality of life (QOL) in patients with stroke, and assessing patient’s satisfaction. Methods: A total of 98 patients with first-ever stroke were included in the study and followed up by for 3 months. This interventional 2-phase study was conducted sequentially at two different university hospitals. Patients in intervention group (IG) was given education by clinical pharmacist and patient in control group (CG) was only given routine care. Medication adherence and QOL was assessed at discharge day, 1st and 3rd month after discharge. Results: The increase in treatment adherence of the patients in IG was significant over time (p<0.001). The scores of the patients in IG from the ‘energy’ and ‘work/productivity’ subscales at 1st and 3rd months after discharge were higher than the patients in CG (p<0.05). The patient’s satisfaction in IG was also higher than the patients in CG (p<0.001). Conclusion: Clinical pharmacist-led education is beneficial to improve treatment adherence and patient’s satisfaction in patients with first ever stroke. Clinical pharmacist should be integrated to improve QOL and treatment adherence multidisciplinary team consisting physician, nurse and physiotherapist. Further studies are needed to assess the impact of clinical pharmacists’ interventions on protection from the second stroke of these patients.
Pulmonary artery and pulmonary valve sarcoma are malignant and very rare vascular tumors with aggressive clinical course and very poor outcomes. Patients affected by coronavirus disease of 2019 (COVID-19) are at higher risk for thromboembolism complication. we describe young woman with history of corona virus pneumonia and progressive dyspnea, hemodynamic disturbance, edema with initial evaluation and clinical diagnosis of pulmonary thromboembolism. But further imaging study and pathology demonstrated, Giant sarcoma of pulmonary valve, obstructing pulmonary valve and extending to right ventricular outflow tract and main of pulmonary artery.