Determining The Effects of Fulvic acid on Biofilm/Planktonic Streptococcus Mutans Growth

poster abstractFulvic acid, a major organic compound extract of Shilajit has been the focus of dental research for the past few years. Shilajit, a sticky tar-like substance of dark brownish color, was used during the ancient times, thousands of years ago and continues to be the traditional method today in India to aid with curing bone/cartilage diseases. Shilajit has also been proven to have anti-inflammatory and pain suppressing effects. This experiment determined the minimum inhibitory concentration (MIC), which is the lowest concentration of fulvic acid, an active component of shilajit that inhibits the visible growth of S. mutans. This experiment also determined the minimum bactericidal concentration (MBC) which is the lowest concentration of fulvic acid that kills S. mutans. A 3-day procedure to determine the growth vs inhibition of the S. mutans was conducted and bacterial readings were recorded using a spectrophotometer after treating S. mutans with 10% formaldehyde, crystal violet stain, and iso-propanol with 30-45 minute incubations between each. The experiment determined that very high concentrations of fulvic acid killed S. mutans, while less concentrated fulvic acid inhibited the growth of S. mutans bacterial cells. A solution comprised of a 5% concentration of fulvic acid killed all of the S. mutans; 5.00%, 2.50%, and 1.25% fulvic acid concentrations had bacterial absorbance of 0.000, 0.009, and 0.027, respectively, as compared to the control group’s normal bacterial growth absorbance of 0.254. Additionally, solutions ranging from a two-fold dilution of fulvic acid to six-fold dilution of fulvic acid inhibited the growth of S. mutans. A similar trend was also observed in planktonic and biofilm formation. For all of the above, in the seventh and eighth dilution (0.078% and 0.039% respectively) of the fulvic acid, the growth of S. mutans bacteria was similar to the control group due to the level of dilution. Overall it was observed that fulvic acid is able to kill bacteria in strong concentrations. Additionally it is able to inhibit further growth of bacteria in lower concentrations, but once the solution becomes too dilute, it does not have an effect on bacterial growth. This contributes greatly to the field of oral health because this data can be utilized for further research on oral bacterial growth inhibitors. Furthermore, the data collected here is a significant starting point for research on the specific minimum concentrations necessary to inhibit oral bacteria growth, because this can be used to determine the smallest amounts of fulvic acid, the bacteria the human body can handle

Determining the Impact of Demographic Factors on Adherence to Glaucoma Treatment in Patients of African Descent

poster abstractPrimary open-angle glaucoma (POAG) affects approximately 2.5 million Americans. Elevated intraocular pressure (IOP) is the only treatable risk factor to slow the progression of the disease and prevent blindness. Topical ocular hypotensive medications, dispensed in the form of eye drops, are the first line of treatment to reduce IOP. Patients are required to use their eye drops once or twice daily throughout the rest of their lives. Patients of African descent are more vulnerable to this chronic disease, with a prevalence six times higher than patients of European descent. They also have worse adherence to the treatment regimen in general. The main purpose of this study was to determine the impact of education, age, gender, household income, marital status, employment and number of prescribed medications on the adherence to the glaucoma treatment. Twenty-one patients were included and adherence was measured using Medication Event Monitoring System caps, which electronically record every time a patient uses their eye drops. After 4 weeks, patients returned with the caps and the compliance level was recorded. During the initial interview, patients answered a questionnaire about the different factors tested in this study. There was a positive correlation between the compliance percentage and age, with patients who are 70 years or older having the highest compliance levels (82% compared to 62% in the 50s and 60s category). Education also affected compliance, with patients who have a high school degree having a lower compliance at 62% compared to the patients with some college or a bachelor’s degree with compliance of 81%. The employment status was another contributor, with higher compliance in full-time employed patients compared to other employment types. The remaining factors did not contribute to the adherence levels. Overall, education, age, and employment status were the only factors that impacted adherence levels

Improving Adherence in African American Patients through Motivational Interviewing

poster abstractGlaucoma is a chronic disease of the eye and African Americans are more susceptible to the disease compared to other races. The medical treatment of glaucoma requires that patients instill eye drops each day for the rest of their lives. Adherence to this regimen be challenging and has been reported to be worse in patients of African American descent (AD), a segment of the population that is disproportionately affected by the disease. Motivational Interviewing (MI) is a goal-oriented, patient-centered counseling style for eliciting behavior change by helping patients to explore and resolve ambivalence. MI can improve adherence and has been shown to be more effective in minority populations. The purpose of the pilot study was to determine whether MI might improve adherence in glaucoma patients of AD. Thirteen patients of African American descent (AD) who received a clinical diagnosis of open-angle glaucoma were included in the study. Patients were included in the study if they used once-a-day prostaglandin analog eye drops and administered their own medication. Adherence was measured using Medical Event Monitoring System (MEMS) bottles. The cap of these bottles electronically records the date and time at which the bottle is opened. At the initial visit patients were instructed to place the eye medication bottle in the MEMS bottle and to continue to use their medication as they normally would. At the second visit (week 3), baseline adherence was assessed. Patients with adherence levels below 75% (n=9) received MI and those with adherence levels over 75% served as controls (n=4). At the last visit (week 9), patients returned and the final adherence was assessed. Baseline and final adherence were compared in each group using a t-test. In the group who received MI, final adherence (67.9% ± 7.68) was significantly higher than baseline adherence (55.95% ± 22.16) (p=0.03). In the control group, no significant difference between baseline adherence (81.38% ± 5.52) and final adherence (82% ± 17.33) (p=0.46) was observed. These preliminary results suggest that motivational interviewing may be effective in improving adherence in patients of AD with glaucoma

Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Cyclosporin a disrupts notch signaling and vascular lumen maintenance.

Cyclosporin A (CSA) suppresses immune function by blocking the cyclophilin A and calcineurin/NFAT signaling pathways. In addition to immunosuppression, CSA has also been shown to have a wide range of effects in the cardiovascular system including disruption of heart valve development, smooth muscle cell proliferation, and angiogenesis inhibition. Circumstantial evidence has suggested that CSA might control Notch signaling which is also a potent regulator of cardiovascular function. Therefore, the goal of this project was to determine if CSA controls Notch and to dissect the molecular mechanism(s) by which CSA impacts cardiovascular homeostasis. We found that CSA blocked JAG1, but not Dll4 mediated Notch1 NICD cleavage in transfected 293T cells and decreased Notch signaling in zebrafish embryos. CSA suppression of Notch was linked to cyclophilin A but not calcineurin/NFAT inhibition since N-MeVal-4-CsA but not FK506 decreased Notch1 NICD cleavage. To examine the effect of CSA on vascular development and function, double transgenic Fli1-GFP/Gata1-RFP zebrafish embryos were treated with CSA and monitored for vasculogenesis, angiogenesis, and overall cardiovascular function. Vascular patterning was not obviously impacted by CSA treatment and contrary to the anti-angiogenic activity ascribed to CSA, angiogenic sprouting of ISV vessels was normal in CSA treated embryos. Most strikingly, CSA treated embryos exhibited a progressive decline in blood flow that was associated with eventual collapse of vascular luminal structures. Vascular collapse in zebrafish embryos was partially rescued by global Notch inhibition with DAPT suggesting that disruption of normal Notch signaling by CSA may be linked to vascular collapse. However, multiple signaling pathways likely cause the vascular collapse phenotype since both cyclophilin A and calcineurin/NFAT were required for normal vascular function. Collectively, these results show that CSA is a novel inhibitor of Notch signaling and vascular function in zebrafish embryos

Vials: Visualizing Alternative Splicing of Genes

Alternative splicing is a process by which the same DNA sequence is used to assemble different proteins, called protein isoforms. Alternative splicing works by selectively omitting some of the coding regions (exons) typically associated with a gene. Detection of alternative splicing is difficult and uses a combination of advanced data acquisition methods and statistical inference. Knowledge about the abundance of isoforms is important for understanding both normal processes and diseases and to eventually improve treatment through targeted therapies. The data, however, is complex and current visualizations for isoforms are neither perceptually efficient nor scalable. To remedy this, we developed Vials, a novel visual analysis tool that enables analysts to explore the various datasets that scientists use to make judgments about isoforms: the abundance of reads associated with the coding regions of the gene, evidence for junctions, i.e., edges connecting the coding regions, and predictions of isoform frequencies. Vials is scalable as it allows for the simultaneous analysis of many samples in multiple groups. Our tool thus enables experts to (a) identify patterns of isoform abundance in groups of samples and (b) evaluate the quality of the data. We demonstrate the value of our tool in case studies using publicly available datasets