Pediatric high grade gliomas: A comprehensive histopathological, immunohistochemical and molecular integrated approach in routine practice.

Pediatric high grade gliomas have undergone remarkable changes in recent time with discovery of new molecular pathways. They have been added separately in current WHO 2021 blue book. All the entities show characteristic morphology and immunohistochemistry. Methylation data correctly identifies these entities into particular group of clusters. The pediatric group high grade glioma comprises- Diffuse midline glioma, H3K27-altered; Diffuse hemispheric glioma, H3G34-mutant; Diffuse pediatric-type high-grade glioma, H3-wild type & IDH-wild type; Infant hemispheric glioma and Epithelioid glioblastoma/Grade 3 pleomorphic xanthoastrocytoma and very rare IDH-mutant astrocytoma. However it is not always feasible to perform these molecular tests where cost-effective diagnosis is a major concern. Here we discuss the major entities with their characteristic histopathology, immunohistochemistry and molecular findings that may help to reach to suggest the diagnosis and help the clinician for appropriate treatment strategies. We have also made a simple algorithmic flow chart integrated with histopathology, immunohistochemistry and molecular characteristics for better understanding.

Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents.

The study of epigenetic translational modifications had drawn great interest for the last few decades. These processes play a vital role in many diseases and cancer is one of them. Histone acetyltransferase (HAT) and histone deacetylases (HDACs) are key enzymes involved in the acetylation and deacetylation of histones and ultimately in post-translational modifications. Cancer frequently exhibits epigenetic changes, particularly disruption in the expression and activity of HDACs. It includes the capacity to regulate proliferative signalling, circumvent growth inhibitors, escape cell death, enable replicative immortality, promote angiogenesis, stimulate invasion and metastasis, prevent immunological destruction, and genomic instability. The majority of tumours develop and spread as a result of HDAC dysregulation. As a result, HDAC inhibitors (HDACis) were developed, and they today stand as a very promising therapeutic approach. One of the most well-known and efficient therapies for practically all cancer types is chemotherapy. However, the efficiency and safety of treatment are constrained by higher toxicity. The same has been observed with the synthetic HDACi. Natural products, owing to many advantages over synthetic compounds for cancer treatment have always been a choice for therapy. Hence, naturally available molecules are of particular interest for HDAC inhibition and HDAC has drawn the attention of the research fraternity due to their potential to offer a diverse array of chemical structures and bioactive compounds. This diversity opens up new avenues for exploring less toxic HDAC inhibitors to reduce side effects associated with conventional synthetic inhibitors. The review presents comprehensive details on natural product HDACi, their mechanism of action and their biological effects. Moreover, this review provides a brief discussion on the structure activity relationship of selected natural HDAC inhibitors and their analogues which can guide future research to discover selective, more potent HDACi with minimal toxicity.

Targeting the epigenetic reader "BET" as a therapeutic strategy for cancer.

Bromodomain and extraterminal (BET) proteins have the ability to bind to acetylated lysine residues present in both histones and non-histone proteins. This binding is facilitated by the presence of tandem bromodomains. The regulatory role of BET proteins extends to chromatin dynamics, cellular processes, and disease progression. The BET family comprises of BRD 2, 3, 4 and BRDT. The BET proteins are a class of epigenetic readers that regulate the transcriptional activity of a multitude of genes that are involved in the pathogenesis of cancer. Thus, targeting BET proteins has been identified as a potentially efficacious approach for the treatment of cancer. BET inhibitors (BETis) are known to interfere with the binding of BET proteins to acetylated lysine residues of chromatin, thereby leading to the suppression of transcription of several genes, including oncogenic transcription factors. Here in this review, we focus on role of Bromodomain and extra C-terminal (BET) proteins in cancer progression. Furthermore, numerous small-molecule inhibitors with pan-BET activity have been documented, with certain compounds currently undergoing clinical assessment. However, it is apparent that the clinical effectiveness of the present BET inhibitors is restricted, prompting the exploration of novel technologies to enhance their clinical outcomes and mitigate undesired adverse effects. Thus, strategies like development of selective BET-BD1, & BD2 inhibitors, dual and acting BET are also presented in this review and attempts to cover the chemistry needed for proper establishment of designed molecules into BRD have been made. Moreover, the review attempts to summarize the details of research till date and proposes a space for future development of BET inhibitor with diminished side effects. It can be concluded that discovery of isoform selective BET inhibitors can be a way forward in order to develop BET inhibitors with negligible side effects.

Advancing beyond reverse transcriptase inhibitors: The new era of hepatitis B polymerase inhibitors.

Hepatitis B virus (HBV) is a genetically diverse blood-borne virus responsible for chronic hepatitis B. The HBV polymerase plays a key role in viral genome replication within the human body and has been identified as a potential drug target for chronic hepatitis B therapeutics. However, available nucleotide reverse transcriptase inhibitors only target the reverse transcriptase domain of the HBV polymerase; they also pose resistance issues and require lifelong treatment that can burden patients financially. In this study, various chemical classes are reviewed that have been developed to target different domains of the HBV polymerase: Terminal protein, which plays a vital role in the formation of the viral DNA; Reverse transcriptase, which is responsible for the synthesis of the viral DNA from RNA, and; Ribonuclease H, which is responsible for degrading the RNA strand in the RNA-DNA duplex formed during the reverse transcription process. Host factors that interact with the HBV polymerase to achieve HBV replication are also reviewed; these host factors can be targeted by inhibitors to indirectly inhibit polymerase functionality. A detailed analysis of the scope and limitations of these inhibitors from a medicinal chemistry perspective is provided. The structure-activity relationship of these inhibitors and the factors that may affect their potency and selectivity are also examined. This analysis will be useful in supporting the further development of these inhibitors and in designing new inhibitors that can inhibit HBV replication more efficiently.

Impact of preoperative posterior segment evaluation on surgical intervention in camp patients: A retrospective analysis.

Purpose: To retrospectively study impact of preoperative posterior segment evaluation on surgical intervention in camp patients recruited for cataract surgery in Gujarat India. Methods: Retrospective analysis of six months data collected from hospital electronic medical record (EMR) system of 9820 admitted patients recruited from screening camp for cataract surgery from 1/10/2019 to 31/3/2020 in Tertiary Eye Hospital in Gujarat, India, has been done. Comprehensive clinical evaluation, of both anterior and posterior segment which included detailed history; best corrected visual acuity (BCVA); intraocular pressure measurement with non-contact tonometer (NCT) and when required with Goldman applanation tonometer; slit lamp examination; and fundus examination with + 90 diopter lens as well as indirect ophthalmoscope as and when indicated. In case there was no view of retina, a B-scan ultrasound was done to rule out any posterior segment pathology. Immediate surgical intervention done was assessed and results analyzed in percentage. Results: Cataract surgery was advised for 8390 patients (85.43%). Surgical intervention for management of glaucoma was done for 68 patients (0.692%). Retina intervention was done for 86 patients. Posterior segment evaluation changed immediate surgical plane of management for 154 (1.57%) patients. Conclusion: Comprehensive clinical evaluation is economical and should be mandatory especially in community services as comorbid conditions like glaucoma, diabetic retinopathy, retinal vein occlusion, and other varied posterior segment diseases contribute significantly to visual disability in elderly age group. It is difficult to follow these patients later if manageable comorbidity is not informed about and if indicated dealt simultaneously for visual rehabilitation of patient.

A perspective on oligonucleotide therapy: Approaches to patient customization.

It is estimated that the human genome encodes 15% of proteins that are considered to be disease-modifying. Only 2% of these proteins possess a druggable site that the approved clinical candidates target. Due to this disparity, there is an immense need to develop therapeutics that may better mitigate the disease or disorders aroused by non-druggable and druggable proteins or enzymes. The recent surge in approved oligonucleotide therapeutics (OT) indicates the imminent potential of these therapies. Oligonucleotide-based therapeutics are of intermediate size with much-improved selectivity towards the target and fewer off-target effects than small molecules. The OTs include Antisense RNAs, MicroRNA (MIR), small interfering RNA (siRNA), and aptamers, which are currently being explored for their use in neurodegenerative disorders, cancer, and even orphan diseases. The present review is a congregated effort to present the past and present of OTs and the current efforts to make OTs for plausible future therapeutics. The review provides updated literature on the challenges and bottlenecks of OT and recent advancements in OT drug delivery. Further, this review deliberates on a newly emerging approach to personalized treatment for patients with rare and fatal diseases with OT.

Comprehensive Review on Different Analytical Techniques for HIV 1- Integrase Inhibitors: Raltegravir, Dolutegravir, Elvitegravir and Bictegravir.

The advent of HIV-Integrase inhibitors (IN) has marked a significant impact on the lives of HIV patients. Since the launch of the first anti retro-viral drug "Azidothymidine" to the recent advances of IN inhibitors, about 27.4 million people benefit by antiretroviral therapy (ART). The path had been challenging due to many crossroads, leading to the discovery of newer targets. One such recent ART target is Integrase. Use of Integrase inhibitors has surpassed the usage of all other ART owing to a strong barrier to resistance and have been reported to be the first-line therapy. Raltegravir, Elvitegravir, Dolutegravir and Bictegravir are US FDA approved IN inhibitors. The high usage of ART created an opportunity to study various analytical techniques for IN inhibitors. Hitherto, no review encompassing all IN inhibitors is presented. Herein, this review describes the analytical techniques employed for IN inhibitors estimation and quantification reported in the literature and official compendia. Literature suggests that most studies focus on LC-MS/MS and HPLC methods for drug estimation, and few reports suggest spectrophotometric, spectrofluorimetric and electrochemical methods. Furthermore, the review presents the techniques that describe the quantification of integrase drugs in various matrices. Although, antiretroviral drugs are extensively used but data suggests that limited studies have been conducted for determination of impurity profile and stability. This therefore, presents a scope to detect and validate impurities in order to meet ICH guidelines for their limits and further to improve the quality and safety of antiretroviral drugs.

Advances in the colon-targeted chitosan based multiunit drug delivery systems for the treatment of inflammatory bowel disease.

Chitosan is the polymer of choice for delivery of the active moieties to the colon due to its cationic nature that enables strong mucosal attachment. Chitosan is explored for formulations such as pellets, beads, microspheres, nanoparticles and drug-polymer conjugates for colon targeting of various therapeutic agents in inflammatory bowel disease (IBD). The major challenge in the colonic delivery of drugs in IBD is altered physiological pH, which can be addressed via chitosan containing multiparticulate drug delivery systems owing to their biodegradability in the colon. Its ionic interaction with anionic polymers forms gastro-resistant multi-unit systems that ensures safe delivery of payloads to the colon. In contrast to commercial grade gastro-resistant polymers, chitosan has GRAS (generally regarded as safe) status that ensures safety for long-term therapy in case of chronic diseases such as IBD. Here, we review in detail essential properties of chitosan and chitosan based multiunit formulations for treatment/mitigation of IBD.

Fecal microbiota transplantation for induction of remission, maintenance and rescue in patients with corticosteroid-dependent ulcerative colitis: a long-term follow-up real-world cohort study.

BACKGROUND/AIMS: To study role of fecal microbiota transplantation (FMT) in induction, maintenance, and rescue in patients with corticosteroid-dependent ulcerative colitis (CDUC). METHODS: Patients with active CDUC received 3 fortnightly sessions of colonoscopic induction FMT (iFMT) in addition to standard of care. In patients who achieved clinical remission (CR) or response, prednisolone was tapered from week 4 and azathioprine from week 12. Responders were advised maintenance FMT (mFMT) every 6 months. Those with relapse were offered rescue FMT (rFMT), and low dose prednisolone was added if there was no improvement in 2 weeks. RESULTS: All 27 patients enrolled completed iFMT and were followed up for 39 months (range, 9-71 months). The mean Mayo score decreased from 6.4±2.5 at baseline to 2.6±3.7 at week 4, 2.6±3.4 at week 12, and 2.8±3.8 at week 24 (P<0.05). Corticosteroid-free CR and clinical response at week 12 were seen in 13 patients (48%) and 1 patient (3.7%), respectively. Corticosteroid and azathioprine-free CR at week 24 was seen in 13 patients (48%) and in them histological response was seen in 2 patients (15.2%) at week 4, 5 patients (38.4%) at week 12, and 10 patients (76.9%) at week 24. First relapse was seen in 10 of 13 responders (76.9%) at a median of 14.8 months (range, 6-34 months) after iFMT and was less frequent in patients on mFMT. Relapse was treated successfully with rFMT alone in 4 patients (40%) and rFMT with low dose steroids in 5 patients (50%). CONCLUSIONS: iFMT, mFMT, and rFMT may have a role in treatment of selected patients with CDUC.

Radial EBUS-Guided Cryobiopsy of Peripheral Lung Lesions With Flexible Bronchoscopy Without Using Guide-Sheath.

BACKGROUND: A guide-sheath (GS) is conventionally used as a conduit for biopsy forceps under the guidance of radial endobronchial ultrasound (REBUS) for sampling the peripheral pulmonary lesions (PPLs). As compared with forceps, the cryoprobe has the advantage of obtaining larger samples. There is a paucity of literature on the use of cryobiopsy for PPL. We evaluated the diagnostic yield and safety of the REBUS-guided cryobiopsy (REBUS-CB) without using GS for the diagnosis of PPL. METHODS: We retrospectively analyzed the database of 126 patients with PPL between November 2015 and December 2019. The REBUS-CB was performed using a flexible bronchoscopy without GS. Multidisciplinary consensus diagnostic yield was determined and procedural complications were recorded. RESULTS: The histopathologic diagnosis by REBUS-CB, which is the primary objective of the study was obtained in 99 (78.6%) of total 126 cases. Yield was significantly higher in central lesions as compared to adjacent lesions visualized by the REBUS probe (81.4% versus 53.8%, P=0.021) but not significantly different between large (≥30 mm) and small (<30 mm) lesions (81.6% versus 71.8%, P=0.214). The average largest diameter of biopsy specimens was 6.9 mm (range 1-12, SD 2.132). We witnessed moderate bleeding in 7 (5.6%) and post procedure hypoxic respiratory failure in 4 (3.2%) cases which could be managed without escalation of care. CONCLUSION: The REBUS-CB from peripheral lung lesions are feasible even without using GS and significantly large samples can be obtained.

Safety and diagnostic yield of transbronchial lung cryobiopsy by flexible bronchoscopy using laryngeal mask airway in diffuse and localized peripheral lung diseases: A single-center retrospective analysis of 326 cases.

BACKGROUND: Intubation with either an endotracheal tube or a rigid bronchoscope is generally preferred to provide airway protection as well as to manage unpredictable complications during transbronchial lung cryobiopsy (TBLC). The laryngeal mask airway has been described as a safe and convenient tool for airway control during bronchoscopy. AIMS AND OBJECTIVES: In this study, we evaluated the safety and outcome of using a laryngeal mask airway (LMA) as a conduit for performing TBLC by flexible video bronchoscopy (FB). METHODS: We retrospectively analyzed the database of the patients who underwent TBLC between November 2015 and September 2019. The procedure was performed using FB through LMA under general anesthesia. Prophylactic occlusion balloon was routinely used starting January 2017 onwards. Radial endobronchial ultrasound (R-EBUS) guidance was used for TBLC in the localized lung lesions when deemed necessary. Multidisciplinary consensus diagnostic yield was determined and periprocedural complications were recorded. RESULTS: A total of 326 patients were analysed. The overall diagnostic yield was 81.60% (266/326) which included a positive yield of 82.98% (161/194) in patients with diffuse lung disease and 79.54% (105/132) in patients with localized disease. Serious bleeding complication occurred in 3 (0.92%) cases. Pneumothorax was encountered in 8 (2.45%) cases. A total of 9 (2.76%) cases had at least 1 major complication. CONCLUSION: This study demonstrates that the use of LMA during TBLC by flexible bronchoscopy allows for a convenient port of entry, adequate airway support and effective endoscopic management of intrabronchial haemorrhage especially with the use of occlusion balloon.

Design, Synthesis and Evaluation of 2,4,6-substituted Pyrimidine Derivatives as BACE-1 Inhibitor: Plausible Lead for Alzheimer's Disease.

Alzheimer's disease is one of the most common neurodegenerative disorder afflicting a large mass of population. BACE-1 (ß-secretase) is an aspartyl protease of the amyloidogenic pathway considered responsible for Alzheimer's disease (AD). Since it catalyzes the rate-limiting step of Aß-42 production from amyloid precursor protein (APP), its inhibition is considered a viable therapeutic strategy. We have reported the design of small molecular weight compounds supposed to be blood brain permeable as BACE-1 inhibitors. The clue for the design of this series is drawn from the previously designed series from our research group. OBJECTIVE: Design and synthesis of 2,4,6-substituted pyrimidine derivatives has been reported. In vitro FRET-based screening of synthesized derivatives was performed to evaluate the BACE-1 inhibition profile. METHODS: Based on the docking simulation studies, a library of derivatives was designed, synthesized and evaluated for BACE-1 inhibition in-vitro. The docking studies were performed on Glide (Schrodinger suite) and Molegro virtual docker. Theoretical toxicity was predicted using Osiris Property Explorer. The synthesized compounds were tested for BACE-1 inhibition using in vitro assay based on Fluorescence Resonance Energy Transfer technique. The percent inhibition was calculated as a measure of activity. RESULTS: The designed compounds revealed strong interactions with the desired amino acids of BACE-1 active sites. The aromatic rings placed at the fourth and sixth position of the pyrimidine ring occupied S1 and S3 substrate-binding clefts while the amino group formed hydrogen bonding interactions with Asp32 and Asp228. In silico data ensured that the compounds were orally bioavailable and brain permeable. The in vitro testing showed that the compounds inhibited BACE-1 at 10µM concentration. CONCLUSION: Compounds substituted with m-benzyloxy on one aromatic ring and o,p-di-chloro on another aromatic ring displayed maximum BACE-1 inhibition. Compound 2.13A displayed high docking score and was found to be most potent with IC50 of 6.92µM. The series displayed a good correlation between the docking score and BACE-1 inhibition profile.

Harnessing Drug Repurposing for Exploration of New Diseases: An Insight to Strategies and Case Studies.

BACKGROUND: Traditional drug discovery is time consuming, costly, and risky process. Owing to the large investment, excessive attrition, and declined output, drug repurposing has become a blooming approach for the identification and development of new therapeutics. The method has gained momentum in the past few years and has resulted in many excellent discoveries. Industries are resurrecting the failed and shelved drugs to save time and cost. The process accounts for approximately 30% of the new US Food and Drug Administration approved drugs and vaccines in recent years. METHODS: A systematic literature search using appropriate keywords were made to identify articles discussing the different strategies being adopted for repurposing and various drugs that have been/are being repurposed. RESULTS: This review aims to describe the comprehensive data about the various strategies (Blinded search, computational approaches, and experimental approaches) used for the repurposing along with success case studies (treatment for orphan diseases, neglected tropical disease, neurodegenerative diseases, and drugs for pediatric population). It also inculcates an elaborated list of more than 100 drugs that have been repositioned, approaches adopted, and their present clinical status. We have also attempted to incorporate the different databases used for computational repurposing. CONCLUSION: The data presented is proof that drug repurposing is a prolific approach circumventing the issues poised by conventional drug discovery approaches. It is a highly promising approach and when combined with sophisticated computational tools, it also carries high precision. The review would help researches in prioritizing the drugrepositioning method much needed to flourish the drug discovery research.

Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors.

Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and GSK3ß. However, GSK3ß is highly expressed in different areas of the brain and has been implicated in Alzheimer's disease as it is involved in tau phosphorylation. Due to its high specificity concerning substrate recognition, GSK3 has been considered as an important target. In the last decade, several GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the information published in the last decade about the role of GSK3 in Alzheimer's disease and progress in the development of its inhibitors. Using this collated information, medicinal chemists can strategize and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer's disease.

Parental Perception of the Importance of the Permanent First Molar in Their Children.

Purpose: To evaluate parental knowledge of the importance of the permanent first molar (PFM).
Methods: Three hundred and eighty parents filled a 22-item questionnaire assisted by a trained investigator. They were asked to indicate the correct answer from the given list of options in order to assess their awareness about the eruption sequence of primary and permanent teeth and the importance of PFMs. Assessment of parental attitude toward preventive management and treatment of carious or infected permanent teeth was done, together with their willingness to comply with the treatment options suggested for such teeth. The sequelae of caries in PFM and their effect on the growth and development of the face and jaws were assessed as well.
Results: Seventy-five percent and 72.4 percent of parents responded correctly about the number of primary and permanent teeth. When parents were asked about the chronology of tooth eruption, 53.9 percent of parents thought that the PFM erupted between 10 and 12 years of age. Almost 65 percent of the parents said they would start brushing their child's teeth after all the primary teeth erupt. Forty-five percent agreed to the extraction of PFMs, considering them to be primary teeth, as they felt unnecessary to treat a carious tooth that was going to exfoliate.
Conclusion: Parents often based their decision for dental treatment choices for their children on lack of information as they were unaware about the eruption and importance of PFM. There is a need to emphasize the importance of PFM during interaction with parents.

Evaluation of the association between tuftelin gene polymorphism, Streptococcus mutans, and dental caries susceptibility.

CONTEXT: Dental caries can be conceptualized as an interaction between genetic and environmental factors. AIMS: The purpose of this study was to identify any polymorphism in tuftelin gene and its association with dental caries susceptibility, either singly or in combination with the microbial causing agent: Streptococcus mutans. SETTINGS AND DESIGN: The presented study included a total of 30 children of age group 12-16 years categorized into two groups: 15 children with no detectable caries in Group I and 15 children with high caries (DMFS ≥10) in group II. MATERIALS AND METHODS: The stimulated salivary samples were inoculated in mitis salivarius bacitracin agar plates and growth of S. mutans was estimated. DNA extraction was done from whole blood and amplification was done with the help of real-time polymerase chain reaction technique. Oligonucleotide primers were designed to flank single nucleotide polymorphism in the gene. STATISTICAL ANALYSIS USED: The collected data was statistically analyzed by unpaired t-test, paired t-test, Chi-square test, Pearson correlation, and regression analysis. RESULTS: The difference in mean salivary S. mutans counts between the two groups was highly significant. Correlation between tuftelin gene polymorphism and dental caries susceptibility was not significant in both Group I and Group II. Only 4.1% of the variability in dental caries risk can be explained by interaction between tuftelin gene and S. mutans. CONCLUSIONS: Future research studies including parents and siblings should be carried out to focus on further investigation into the mechanism of this gene-environment interaction.

Quinoline, Coumarin and Other Heterocyclic Analogs Based HIV-1 Integrase Inhibitors.

Human Immunodeficiency Virus Type 1 Integrase or HIV-1 integrase (IN) is a 288 amino acid protein that incorporates the retrotranscribed viral DNA into the host chromosomal DNA. Over the past 30 years, large number of derivatives have been evaluated for their inhibitory potential against IN. There is vast literature available which need to be collated to help scientists plan the future drug design. This review discusses the reports of past 25 years on analogs of quinoline, coumarin and other related heterocycles, which exhibit low micromolar inhibitory potency against IN.

Robinow Syndrome and Fusion of Primary Teeth.

Managing patients with rare genetic disorders is a challenge that dentists face often. Robinow syndrome (RS) is one such rare genetic disorder with <200 cases reported worldwide. RS demonstrates multiple craniofacial abnormalities and orodental disorders, which need to be taken into consideration by a dental practitioner while rendering dental care.

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India.

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm3, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.

Design, synthesis and in vitro evaluation studies of sulfonyl-amino-acetamides as small molecule BACE-1 inhibitors.

The identification of a series of sulfonyl-amino-acetamides as BACE-1 (ß-secretase) inhibitors for the treatment of Alzheimer's disease is reported. The derivatives were designed based on the docking simulation study, synthesized and assessed for BACE-1 inhibition in vitro. The designed ligands revealed desired binding interactions with the catalytic aspartate dyad and occupance of S1 and S2' active site regions. These in silico results correlated well with in vitro activity. Out of 33 compounds synthesized, 12 compounds showed significant inhibition at 10µM concentration. The most active compound 2.17S had IC50 of 7.90µM against BACE-1, which was concomitant with results of in silico docking study.