DNASCANNER v2: A Web-Based Tool to Analyze the Characteristic Properties of Nucleotide Sequences.

Throughout the process of evolution, DNA undergoes the accumulation of distinct mutations, which can often result in highly organized patterns that serve various essential biological functions. These patterns encompass various genomic elements and provide valuable insights into the regulatory and functional aspects of DNA. The physicochemical, mechanical, thermodynamic, and structural properties of DNA sequences play a crucial role in the formation of specific patterns. These properties contribute to the three-dimensional structure of DNA and influence their interactions with proteins, regulatory elements, and other molecules. In this study, we introduce DNASCANNER v2, an advanced version of our previously published algorithm DNASCANNER for analyzing DNA properties. The current tool is built using the FLASK framework in Python language. Featuring a user-friendly interface tailored for nonspecialized researchers, it offers an extensive analysis of 158 DNA properties, including mono/di/trinucleotide frequencies, structural, physicochemical, thermodynamics, and mechanical properties of DNA sequences. The tool provides downloadable results and offers interactive plots for easy interpretation and comparison between different features. We also demonstrate the utility of DNASCANNER v2 in analyzing splice-site junctions, casposon insertion sequences, and transposon insertion sites (TIS) within the bacterial and human genomes, respectively. We also developed a deep learning module for the prediction of potential TIS in a given nucleotide sequence. In the future, we aim to optimize the performance of this prediction model through extensive training on larger data sets.

Efficacy of Caudal Epidural Steroid Injections in Chronic Low Backache Patients.

Background: Caudal epidural steroid injections are the popular treatment for patients with chronic low back aches (LBA) and radiculopathy, pain that radiates down the legs. These injections are typically given in the lower back, and their purpose is to reduce inflammation and pain caused by a herniated disc or other issues in the lumbosacral spine. Studies have generally found that caudal epidural steroid injections effectively manage chronic LBP, although they may not provide long-term relief in all cases. It is essential to remember that these injections should be combined with other forms of conservative management, such as physical therapy, before considering more invasive interventions. Materials and Methods: A prospective analysis is performed at the Orthopedics Department At The Hind Institute Of Medical Sciences In Sitapur, Uttar Pradesh, India, over two years. In the study, 80 patients with chronic low back pain and symptoms that did not improve with conservative therapies. The patients are clinically examined before and after receiving a cervical epidural steroid injection (CESI) based on their ability to perform daily activities and work using the Oswestry disability index (ODI) and visual analog scale (VAS). Results: The experiment was conducted with 165 CESI administered to 120 patients. A single injection is given to 85 patients; two injections are given to 25 patients, and 10 patients receive three injections. Of the 120 patients, 50 were male, and 70 were female, all of whom had chronic LBA. Of the 120 cases of LBA, 37 were diagnosed with lumbar disc herniation, 11 with lumbar canal stenosis, and 22 with degenerative disc disease. The remaining 50 cases were classified as non-specific LBA. Follow-up evaluations were conducted 1 week, 1 month, and 3 months after that, till 12 months of treatment. The mean pre-CESI VAS score was 7.11, and the mean post-CESI VAS score was 4.82 after one year of treatment. The mean ODI score before CESI treatment was 59.12; after CESI treatment for a full year, it was 44.64. We observed excellent outcomes in 27.5% of patients, good outcomes in 38.33%, fair outcomes in 21.67%, and bad outcomes in 12.5% of patients. Conclusion: Patients who experience chronic function aches can dramatically reduce their discomfort with the help of CESIs.

Right Superior Ophthalmic Vein Thrombosis Induced by Pansinusitis.

Superior ophthalmic vein thrombosis (SOVT) is a rare, sight-threatening condition. It can be clinically challenging to distinguish from pre-septal cellulitis or cavernous sinus thrombosis. Imaging is often a key to identifying SOVT, and multi-disciplinary input is paramount to ensuring the optimum outcome. This often involves the paediatricians, ophthalmologists and paediatric neurologists if necessary. We report a case of a young boy with right SOVT that had initially been diagnosed as pre-septal cellulitis. A contrast-enhanced computed tomography scan was performed, as the patient developed limited eye movement on elevation, which showed dilatation of the right ophthalmic vein with pansinusitis. He was successfully treated with anticoagulation and antibiotics.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

BACKGROUND: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. METHODS: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as "failing" standard dosing at 42 weeks who were not dose escalated. RESULTS: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. CONCLUSION: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

Novel Nondietary Therapies for Celiac Disease.

Celiac Disease (CeD) is defined as a chronic small intestinal immune-mediated enteropathy that is precipitated by exposure to dietary gluten in genetically predisposed individuals. CeD is one of the most common autoimmune disorders affecting around 1% of the population worldwide. Currently, the only acceptable treatment for CeD is strict, lifelong adherence to a gluten-free diet (GFD) which can often present a challenging task. A GFD alone is not sufficient to control symptoms and prevent mucosal damage that can result from unintentional gluten exposure. Moreover, long-term complications can occur in many patients. Consequently, there is an unmet need for non-dietary therapies for the management of CeD. Such therapies could serve as an adjunct to the GFD but eventually may replace it. This review will focus on and discuss non-dietary therapies currently in clinical development for the management of CeD. METHODOLOGY: We searched clinicaltrials.gov and PubMed to extract articles about celiac disease. We used keywords including, but not limited to, "celiac disease," "non-dietary," "therapeutics," "pathophysiology," "Endopeptidases," "tight junction modulators," "vaccine," and "Nexvax2". We focused mainly on articles that conducted pathophysiologic and therapeutic research in human trials.

Meta-analysis of dye-based chromoendoscopy compared with standard- and high-definition white-light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer.

BACKGROUND: Patients with ulcerative colitis have an increased risk of colorectal cancer. We sought to assess the comparative efficacy of standard white-light endoscopy (SDWLE) or high-definition white-light endoscopy (HDWLE) versus dye-based chromoendoscopy through a meta-analysis and rate the quality of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. METHODS: A systematic review of the literature in PubMed, EMBASE, and Web of Science was performed in April 2018. The primary outcome was the number of patients in whom dysplasia was identified using a per patient analysis in randomized controlled trials (RCT) and analyzed separately for non-RCTs. Analysis was performed using RevMan 5.3 reporting random-effects risk ratios. RESULTS: Of the 27,904 studies identified, 10 studies were included 6 of which were RCTs (3 SDWLE and 3 HDWLE). Seventeen percent (84/494) of patients were noted to have dysplasia using chromoendoscopy compared with 11% (55/496) with white-light endoscopy (relative risk [RR] 1.50; 95% confidence interval [CI], 1.08-2.10). When analyzed separately, chromoendoscopy (n = 249) was more effective at identifying dysplasia than SDWLE (n = 248) (RR, 2.12; 95% CI, 1.15-3.91), but chromoendoscopy (n = 245) was not more effective compared with HDWLE (n = 248) (RR, 1.36; 95% CI, 0.84-2.18). The quality of evidence was moderate. In non-RCTs, dysplasia was identified in 16% (114/698) of patients with chromoendoscopy compared with 6% (62/1069) with white-light endoscopy (RR, 3.41; 95% CI, 2.13-5.47). Chromoendoscopy (n = 58) was more effective than SDWLE (n = 141) for identification of dysplasia (RR, 3.52; 95% CI, 1.38-8.99), and chromoendoscopy (n = 113) was also more effective than HDWLE (n = 257) (RR, 3.15; 95% CI, 1.62-6.13). The quality of the evidence was very low. CONCLUSION: Based on this meta-analysis, non-RCTs demonstrate a benefit of chromoendoscopy over SDWLE and HDWLE, whereas RCTs only show a small benefit of chromoendoscopy over SDWLE, but not over HDWLE.

Variations in Insurance Policies Regarding Adherence to the AGA Guideline for Therapeutic Drug Monitoring in IBD.

BACKGROUND: The American Gastroenterological Association (AGA) published guidelines on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) in August 2017 recommending use of reactive TDM to guide treatment changes in patients with active IBD who are being treated with anti-tumor necrosis factor (anti-TNF) agents or thiopurines. We sought to determine if changes in national clinical practice guidelines result in changes in health care insurance policies within 6 months of publication. METHODS: Using the National Association of Insurance Commissioners Market Share Reports of the top 125 insurance companies by market share in 2016, we reviewed the largest 50 companies for their publicly available online policies regarding TDM of anti-TNF and thiopurine in IBD. For those with available policies, we looked for whether proactive and/or reactive TDM was covered. Policies were also looked for genetic or enzymatic activity of thiopurine methyltransferase (TPMT) testing before use of thiopurine. All these policies were reviewed within the week of publication of the AGA guideline. They were reviewed again 1, 3, and 6 months later for evaluation of any policy changes after the published AGA guidelines. RESULTS: Fifty of the largest insurance company policies were included. With regards to TDM policy for anti-TNF, we did not find a difference between baseline and 6 months values (P=0.38). With regards to TDM policy for thiopurine, we did not find a difference between baseline and 6 months values (P=1.00). About half of the companies did not have a policy regarding TPMT testing for thiopurine use. Of those with available policies for TPMT testing, there was no difference between baseline and 6 months values (P=0.13). CONCLUSIONS: Even after publication of national guidelines, a large number of the largest health insurance companies do not have a policy regarding reactive TDM for anti-TNF and/or thiopurines. Majority of those with a policy, fail to meet the current standards set forth by the practice guidelines. A significant gap remains between the insurance policies and AGA guidelines. Further studies are needed to determine how to effectuate change to improve insurance company adherence to clinical practice guidelines.

Meta-analysis comparing the efficacy and adverse events of biologics and thiopurines for Crohn's Disease after surgery for ulcerative colitis.

BACKGROUND: Long-term inflammatory complications of IPAA include Crohn's Disease (CD) or "CD-like" (CDL) condition. We performed a meta-analysis to evaluate the efficacy of anti-tumor necrosis factor (anti-TNF) with or without immunomodulator (IM) therapy in this group of patients. METHODS: Literature databases were searched from inception to October 4, 2017. Further searches using references from papers of interest were conducted and, abstracts from major GI conferences were searched. The primary endpoint was: complete clinical response in the two arms. RESULTS: Out of 9 identified studies 4 were included for quantitative analysis. 48% (84/175) were female and mean age was 30.7 years. There was no significant difference in complete clinical response rates, RR 0.58 (95%CI 0.13-2.54, p = 0.5) or partial clinical response rates of RR 0.98 (95%CI 0.52-1.83, p = 0.94). All patients achieved endoscopic and deep remission in the only study reporting these outcomes comparatively in the two arms. There was a trend towards higher risk of major [RR 3.89, (95%C 0.92-16.45 p = 0.09)], and minor adverse events [RR 3.07 (95%CI 0.7-13.52 p = 0.28)] when using anti-TNF therapy compared to anti-TNF with IM. CONCLUSION: We found no difference in outcomes with anti-TNF monotherapy compared to concurrent anti-TNF therapy with IM. Additional studies are needed to define the optimal therapy for CD after IPAA.

Biologics and immunomodulators for treating Crohn's disease developing after surgery for an initial diagnosis of ulcerative colitis: a review of current literature.

Crohn's Disease (CD) or CD-like (CDL) conditions of the pouch are rare long-term inflammatory complications of patients who were initially diagnosed with ulcerative colitis (UC) who undergo total proctocolectomy with ileo-anal anastomosis (IPAA). There are no societal guidelines nor a consensus on their treatment, resulting in significant challenges for clinicians for their diagnosis and management. It is important to differentiate them from other more common pouch-related complications like pouchitis, cuffitis, irritable pouch syndrome, surgery associated stricture, and fistula. In this review, we focus on the less common presentation of CD and CDL conditions of the pouch and their treatment with the use of anti-TNF therapy with or without immunomodulator.

Anomalous Lateral Rectus Muscle Band in a Case of Duane Retraction Syndrome.

Anomalous orbital structures are suspected in restrictive strabismus with features of severe globe retractions, overshoots, or synergistic movements. We report a case of suspected Duane syndrome that was found to have an anomalous band beneath the lateral rectus muscle. Such abnormal structures are rare, but it is important to identify and manage them to optimize outcomes.

Variations in Health Insurance Policies Regarding Biologic Therapy Use in Inflammatory Bowel Disease.

BACKGROUND: The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. METHODS: Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available. Policies were reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and for compliance with the current AGA clinical pathway recommendations. RESULTS: Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis pathway and require step-wise drug failure before approval of an anti-TNF. Only 11% of the policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 21% required the failure of two or more anti-TNF agents. Ninety percent of the policies are inconsistent with AGA CD pathway and require step-wise drug failure before approval of an anti-TNF. Seventy-four percent allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight percent required failing of at least two or more drugs before starting anti-TNF. Only 8% policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 28% required the failure of two anti-TNF agents. CONCLUSIONS: The majority of the policies reviewed fail to adhere to the current AGA pathway recommendations for ulcerative colitis and CD. Further interventions are needed to better align policies with optimal evidence-based drug therapy.

Current and novel therapeutic strategies in celiac disease.

INTRODUCTION: A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD. AREAS COVERED: We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including 'celiac disease' and 'refractory celiac disease' (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.

Impact of hyperbaric oxygen on diabetic ulcers is unaffected by glycemic control.

Hyperbaric oxygen (HBO2) therapy is an established intervention for treating chronic diabetic lower extremity ulcers, but the impact of glycemic control on its efficacy has not been determined. The purpose of this study was to evaluate the impact of blood glucose control at initiation of HBO2 treatment on wound healing. Hemoglobin A1c (HbA1c) was measured at start of HBO2 therapy for 22 patients undergoing treatment of chronic lower extremity ulcers at two regional wound care centers. Patients with HbA1c < 7.5% were stratified into a "good glycemic control" group (n = 12, mean HbA1c 6.5 ± 0.8%), and patients with HbA1c ≥ 7.5% were stratified into a "poor glycemic control" group (n = 10, mean HbA1c 8.8 ± 1.4%, p = 0.004 compared to "good glycemic control group"). After 20 HBO2 sessions over 30 days in addition to standard wound care interventions, there was no difference in wound healing between the two glycemic control groups as indicated by. reduction from baseline in ulcer surface area, depth, or volume. The diabetic lower extremity wound response to HBO2 therapy is unaffected by glycemic control prior to treatment, and HBO2 treatment should not be delayed for suboptimal blood glucose control.