Generation of an induced pluripotent stem cell line IGIBi18-A from an Indian patient with Rubinstein Taybi Syndrome.

Rubinstein Taybi Syndrome (RSTS) is a rare genetic disorder which is caused by mutations in either CREBBP or EP300. RSTS with mutations in CREBBP is known as RSTS-1. We have generated an induced pluripotent stem cell (iPSC) line, IGIBi018-A from an Indian RSTS-patient using the episomal reprogramming method. The CREBBP gene in the patient harbours a nonsense mutation at position NM_004380.3(c.6876 del C). IGIBi018-A iPSC showed expression of pluripotent stem cell markers, has a normal karyotype and could be differentiated into three germ layers. This iPSC line will help to explore the role of CREBBP in RSTS associated developmental defects.

Lessons learned from qualitative fieldwork in a multilingual setting.

Qualitative research conducted in a multilingual setting is an arduous, yet essential, endeavour. As part of my PhD research program, I set out to conduct qualitative process evaluation of a stroke trial in 11 languages in the Indian subcontinent. In this article, I reflect upon the challenges, oversights, and successes that I experienced in the hope of offering insight of use to fellow researchers conducting healthcare fieldwork in multicultural contexts where many languages are spoken. My account starts with a description of the setting's context and the necessity of conducting research in multiple languages. I elaborate on the planning of the study which included selection of the sample and preparation of relevant documents, including informed consent in patients' languages. Subsequent steps entailed submission and approval of requisite documents, setup and training of a research team, and conducting interviews using interpreters. During this process, I developed a hybrid technique for conducting interviews that reduced fatigue for both patient interviewees and interpreters while still yielding in-depth insights. Additionally, I discuss the benefits of engaging professional translators for performing translations. Finally, I introduce a stepwise approach to facilitate the thematic analysis of qualitative data. I believe this account will encourage and empower researchers to pave their own way while anticipating and preparing for potential obstacles when conducting research in similar settings.

Phytochemical investigation of Nigella sativa seed extract by HPTLC, HPLC and GC-MS: a comparative geographical study.

This study aimed to ensure the quality of the seed as well as determine the phytochemical composition of Nigella sativa seed extract (NSSE) obtained from three different geographical locations. Pharmacognostic evaluation of the seed includes preliminary phytochemical screening, physicochemical evaluation, and study of heavy metal content, in addition to HPTLC, HPLC, and GC-MS studies of the extract obtained from the seed of the Nigella sativa (NS). HPTLC fingerprinting studies revealed the presence of various bioactive compounds. HPLC analysis confirms the quantitative variation of thymoquinone (TQ) in the extracts, i.e. the maximum quantity of TQ was found in Vizag NSSE, followed by Punjab and Madhya Pradesh. GC-MS analysis reveals the presence of 33, 35, and 32 constituents in the extract obtained from Vizag, Madhya Pradesh, and Punjab, respectively. This study confirms the variation in the phytochemical composition as well as in the biomarker (Thymoquinone) content present in the collected samples.

Quantitative measurement of retinal nerve fiber layer thickness and its correlation with optical coherence tomography angiography vascular biomarker changes in preclinical diabetic retinopathy.

PURPOSE: The present study was done to assess the use of optical coherence tomography angiography (OCTA) in detecting earlier stages of diabetic retinopathy and for the early management and effective blood glucose control in preclinical diabetic patients for preventing retinal nerve fiber layer (RNFL) thinning. METHODS: A tertiary care center-based prospective observational study was conducted from the year 2021 to 2022 in the Department of Ophthalmology. The study included 50 cases and 50 controls. The parameters analyzed by using OCTA (Topcon 3D OCT-1 Maestro2) were RNFL thickness and peripapillary vessel density. RESULTS: We found that the RNFL thickness in the temporal and superior disc in patients with preclinical diabetic retinopathy was significantly (0.041 and 0.044, respectively) decreased. The duration of diabetes and glycated hemoglobin (HbA1c) were the risk factors for peripapillary vessel density reduction in patients with preclinical diabetic retinopathy (P < 0.001). CONCLUSION: RNFL thinning is an early sign of retinal neurodegeneration and is associated with peripapillary vessel density reduction. Early management and effective blood glucose control in diabetes patients may be beneficial for preventing RNFL thinning in superior and temporal disc.

Secondary prevention by structured semi-interactive stroke prevention package in INDIA (SPRINT INDIA): Findings from the process evaluation of a randomized controlled trial.

INTRODUCTION: Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in INDIA Trial delivered secondary stroke awareness intervention to sub-acute stroke patients in form of workbook, videos and SMS across 31 centres in 12 languages. Trial was stopped for futility due to fewer vascular outcomes than anticipated. Trial results indicated that trial intervention, did not lead to reduction in vascular events. We carried out process evaluation, to evaluate trial implementation and participant's perspectives, to comprehend the trial's futile outcomes. MATERIALS AND METHODS: Using mixed methods approach, qualitative interviews and quantitative data from case report forms, workbooks and questionnaires were analysed to measure intervention fidelity and contamination. Using purposive sampling, 115 interviews of patient-caregiver dyads and health professionals at 11 centres and 2 focus group discussions were held. RESULTS AND DISCUSSION: Iterative thematic analysis of qualitative data was done with RE-AIM and realist models. There was good fidelity to intervention and adherence to protocol; however, there was dilution of inclusion criteria by randomly enrolling uneducated and caregiver-dependent patients. Centre coordinators provided counselling to both arms, not specified by protocol, causing bias. Coordinators found it difficult to keep patients motivated to view intervention which was corroborated by fidelity questionnaire showing decreased viewing of intervention for a year. Cardiovascular protection improved in routine care by virtue of participating in trial. No contamination of intervention was reported. CONCLUSION: The intervention was acceptable by patients and caregivers, which could be made a community-based programme. Reasons identified for decreased viewing were repetitive content and non-availability of personal cellular device.

Non-POU Domain-Containing Octomer-Binding (NONO) protein expression and stability promotes the tumorigenicity and activation of Akt/MAPK/ß-catenin pathways in human breast cancer cells.

Breast cancer is one of the most common cancers with a high mortality rate, underscoring the need to identify new therapeutic targets. Here we report that non-POU domain-containing octamer-binding (NONO) protein is overexpressed in breast cancer and validated the interaction of the WW domain of PIN1 with c-terminal threonine-proline (thr-pro) motifs of NONO. The interaction of NONO with PIN1 increases the stability of NONO by inhibiting its proteasomal degradation, and this identifies PIN1 as a positive regulator of NONO in promoting breast tumor development. Functionally, silencing of NONO inhibits the growth, survival, migration, invasion, epithelial to mesenchymal transition (EMT), and stemness of breast cancer cells in vitro. A human metastatic breast cancer cell xenograft was established in transparent zebrafish (Danio rerio) embryos to study the metastatic inability of NONO-silenced breast cancer cells in vivo. Mechanistically, NONO depletion promotes the expression of the PDL1 cell-surface protein in breast cancer cells. The identification of novel interactions of NONO with c-Jun and ß-catenin proteins and activation of the Akt/MAPK/ß-catenin signaling suggests that NONO is a novel regulator of Akt/MAPK/ß-catenin signaling pathways. Taken together, our results indicated an essential role of NONO in the tumorigenicity of breast cancer and could be a potential target for anti-cancerous drugs. Video Abstract.

Ayurvedic Treatment in the Rehabilitation of Ischemic Stroke Patients in India: A Randomized Controlled Trial Study Protocol.

In patients with ischemic stroke, motor and sensory impairments are common and are associated with functional disability. Conventional physiotherapy (CP) is the primary modality of rehabilitation for post-stroke sensorimotor dysfunction. Ayurveda is a commonly practiced alternative system of medicine that offers unique rehabilitative measures for post-stroke recovery. We hypothesize that Ayurvedic rehabilitative treatment (ART) is superior to similar duration CP in improving the sensorimotor recovery of patients with ischemic stroke at 90 days after enrollment. AyuRvedic TrEatment in the Rehabilitation of Ischemic STrOke Patients in India: A Randomized controllEd trial (RESTORE) is an investigator-initiated, multicenter, prospective, randomized, controlled, parallel-arm, blinded outcome assessment trial being conducted under the Indian Stroke Clinical Trial (INSTRuCT) Network across the four comprehensive stroke centers in India. Consecutive hemodynamically stable adult patients with their first acute ischemic stroke between 1 and 3 months from stroke onset are being randomized (1:1) into two treatment groups to receive either 1 month of ART or 1 month of CP. The primary outcome measure is the Fugl Meyer Assessment-upper extremity for physical performance at 90 days. The secondary outcomes are the modified Rankin Scale, Barthel Index, Berg Balance, and SF-36 at 90 days. The safety outcomes include a composite of irreversible morbidity and mortality. A sample size of 140 (70 in each group) patients with ischemic stroke will allow us to detect a minimal clinical important difference of 9.4 (standard deviation) with superiority margin of 5, an attrition rate of 10%, alpha of 5%, and power of 80%. This randomized trial will systematically assess the efficacy and safety of traditional ART compared to CP. The trial has been registered in the Clinical Trial Registry India (CTRI/2018/04/013379).

Circulating Cell-Free DNA Level in Prediction of COVID-19 Severity and Mortality: Correlation of with Haematology and Serum Biochemical Parameters.

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the ß-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6-1258) as compared to MCOV-19 at 219.8 ng/ml (167.7-299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.

Synthesis and CNS Activity of Phenytoin Derivatives.

BACKGROUND: The derivatives of Phenytoin conjugated with various anilines were synthesized. The synthesized derivatives were evaluated for different physicochemical parameters along with log P values using different software programs to discover their ability to cross the blood brain barrier. The pharmacological activities such as antianxiety, skeletal muscle relaxant and anticonvulsant were evaluated by using different models. OBJECTIVE: The new Phenytoin derivatives were synthesized and evaluated for different properties to predict CNS activity. The drugs synthesized by chloroacetylation and then different aniline were added to it. The compounds were evaluated for their different CNS activity by using different methods. METHODS: The compounds were synthesized by firstly chloroacetylating the phenytoin and then different substituted anilines were added to it. The compounds were evaluated for antianxiety activity, muscle relaxant activity and anticonvulsant activity by using different models. RESULTS: The number of derivatives of Phenytoin was synthesized and various physicochemical parameters were optimized which revealed that the compound containing chloro groups such as C2 and C5 exhibited significant potential when compared with the standard drug Diazepam. CONCLUSION: It was portrayed that the synthesis, computational studies and evaluation of anticonvulsant, antianxiety and skeletal muscle relaxant activity of new Phenytoin derivatives were carried out. The compounds were productively synthesized and portrayed by molecular docking studies. The compounds also exhibit mild to moderate similarity with respect to standard drug. The synthesized drugs have the potential to be optimized further to engender new scaffolds to treat various CNS disorders.

Transient Ischemic Attack (TIA) Incidence with Geographic Information Systems (GIS) Mapping for Stroke Prevention Interventions.

OBJECTIVES: GIS mapping as a public health tool has been increasingly applied to chronic disease control. While evaluating TIA incidence from an existing regional stroke registry in Ludhiana city, India, we aim to apply the innovative concept of regional TIA GIS mapping for planning targeted stroke prevention interventions. METHODS: TIA patient data was obtained from hospitals, scan centers and general practitioners from March 2010 to March 2013 using WHO-Stroke STEPS based surveillance as part of establishing a population-based stroke registry in Ludhiana city. From this registry, patients with TIA (diagnosed by MRI image-based stroke rule-out, or clinically) were chosen and data analyzed. RESULTS: A total of 138 TIA patients were included in the final analysis. The annual TIA incidence rate for Ludhiana city was 7.13/100,000 (95% confidence interval: 5.52 to 8.74) for 2012-2013. Mean age was 58.5 ± 13.9 years (range: 22-88 years) and 87 (63%) were men. Majority of the TIA cases had anterior circulation TIAs. Hypertension (87.4%) was the most common risk factor. Using Geographic Information System (GIS) mapping, high TIA incidence was seen in central, western, and southern parts and clustering of TIA cumulative incidence was seen in the central part of Ludhiana city. CONCLUSION: Incidence rate of TIA was lower than that expected from a low- and middle-income country (LMIC). TIA GIS mapping, looking at regional localization, can be a novel option for developing targeted, cost-effective stroke prevention programs.

Systematic review of epigenetic targets in acute myeloid leukemia.

Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal modalities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy.

Synthesis, Physicochemical, Computational and Biological Evaluation of Phenylurea Derivatives as CNS Agents.

BACKGROUND: A series of phenylurea derivatives were designed and synthesized, The target compounds were subjected to pharmacological studies. Various other parameters such as physicochemical properties, computational studies, and % similarity were also calculated. MATERIALS AND METHODS: The synthesis of the target compounds has been carried out by reaction of Phenylurea with chloroacetyl chloride to afford 1-(2-chloroacetyl)-3-phenylurea, which further reacted with substituted anilines. All the reactions were monitored by TLC. All the target compounds were purified by recrystallization and characterized by spectroscopic methods. Physicochemical parameters and Log P values of the synthesized derivatives were also calculated. It identified compounds that have the prospect to cross the blood-brain barrier (BBB) and are CNS active. Skeletal muscle relaxant activity was also carried out using the Rotarod method. RESULTS: The data of Log P indicated that the synthesized compounds have the potential to cross the BBB, so they are CNS active. Pharmacological activities of the derivatives showed that the compounds containing chloro group have moderate skeletal muscle relaxant activity. The test compounds possess significant differences between the control group and the treated group. CONCLUSION: The synthesized derivatives containing chloro group were found to be more potent when compared to standard drug Diazepam. Various others parameters studied revealed that the drug has the potency to cross the blood-brain barrier.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

Systematic Development of Structured Semi-interactive Stroke Prevention Package for Secondary Stroke Prevention.

BACKGROUND: Lack of compliance to medication and uncontrolled risk factors are associated with increased risk of recurrent stroke and acute coronary syndrome in patients with recent stroke. Multimodal patient education may be a strategy to improve the compliance to medication and early adoption of nonpharmacological measures to reduce the vascular risk factor burden in patients with stroke. We thus aim to develop multilingual short messaging services (SMS), print, and audio-visual secondary stroke prevention patient education package. The efficacy of the package will be tested in a randomized control trial to prevent major cardiovascular and cerebrovascular events. METHODS: In the formative stage, intervention materials (SMS, video, and workbook) were developed. In the acceptability stage, the package was independently assessed and modified by the stakeholders involved in the stroke patient care and local language experts. The modified stroke prevention package was tested for implementation issues (implementation stage). RESULTS: Sixty-nine SMS, six videos, and workbook with 11 chapters with 15 activities were developed in English language with a mean ± SD SMOG index of 9.1 ± 0.4. A total of 355 stakeholders including patients (24.8%), caregivers (24.8%), doctors (10.4%), nurses (14.1%), local language experts (2.8%), physiotherapists (13.2%), and research coordinators (9.8%) participated in 10 acceptability stage meetings. The mean Patient Education Material Assessment Tool understandability score in all languages for SMS, video scripts, and workbook was 95.2 ± 2.6%, 95.2 ± 4.4%, and 95.3 ± 3.6%, respectively. The patients [n = 20, mean age of 70.3 ± 10.6 years and median interquartile range (IQR) baseline NIHSS 1 (0-3)] or the research coordinators (n = 2) noted no implementation issues at the end of 1 month. CONCLUSION: An implementable complex multilingual patient education material could be developed in a stepwise manner. The efficacy of the package to prevent major adverse cardiovascular events is being tested in the SPRINT INDIA study.

Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India (SPRINT INDIA) study protocol.

RATIONALE: Recurrent stroke, cardiovascular morbidity, and mortality are important causes of poor outcome in patients with index stroke. Despite the availability of best medical management recurrent stroke occur in up to 15-20% of patients with stroke in India. Education for stroke prevention could be a strategy to prevent recurrent strokes. HYPOTHESIS: We hypothesize that a structured semi-interactive stroke prevention package can reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke at the end of one year. DESIGN: Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in INDIA (SPRINT INDIA) is a multi-center stroke trial involving 25 centers under the Indian Stroke Clinical Trial Network. Patients with first ever sub-acute stroke within two days to three months of onset, age 18-85 years, mRS <5, showing recent stroke in imaging are included. Participants or caregivers able to read and complete tasks suggested in a stroke prevention workbook and have a cellular device for receiving short message service and watching videos. A total of 5830 stroke patients speaking 11 different languages are being randomized to intervention or control arm. Patients in the intervention arm are receiving a stroke prevention workbook, regular educational short messages, and videos. All patients in the control arm are receiving standard of care management. SUMMARY: Structured semi-interactive stroke prevention package may reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke. TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov (NCT03228979) and CTRI (Clinical Trial Registry India; CTRI/2017/09/009600).

Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents.

BACKGROUND: Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products. MATERIALS & METHODS: Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software. RESULTS: The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group. CONCLUSION: Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.

Family-led rehabilitation in India (ATTEND)-Findings from the process evaluation of a randomized controlled trial.

BACKGROUND: Training family carers to provide evidence-based rehabilitation to stroke patients could address the recognized deficiency of access to stroke rehabilitation in low-resource settings. However, our randomized controlled trial in India (ATTEND) found that this model of care was not superior to usual care alone. AIMS: This process evaluation aimed to better understand trial outcomes through assessing trial implementation and exploring patients', carers', and providers' perspectives. METHODS: Our mixed methods study included process, healthcare use data and patient demographics from all sites; observations and semi-structured interviews with participants (22 patients, 22 carers, and 28 health providers) from six sampled sites. RESULTS: Intervention fidelity and adherence to the trial protocol was high across the 14 sites; however, early supported discharge (an intervention component) was not implemented. Within both randomized groups, some form of rehabilitation was widely accessed. ATTEND stroke coordinators provided counseling and perceived that sustaining patients' motivation to continue with rehabilitation in the face of significant emotional and financial stress as a key challenge. The intervention was perceived as an acceptable community-based package with education as an important component in raising the poor awareness of stroke. Many participants viewed family-led rehabilitation as a necessary model of care for poor and rural populations who could not access rehabilitation. CONCLUSION: Difficulty in sustaining patient and carer motivation for rehabilitation without ongoing support, and greater than anticipated access to routine rehabilitation may explain the lack of benefit in the trial. Nonetheless, family-led rehabilitation was seen as a concept worthy of further development.

Use of "Surface Analyzer" to evaluate the Effect of Two Polishing Systems on Surface Texture of Four Newer Composites.

Composites polymerized with a clear matrix on the surface will leave a resin-rich surface layer that is easily abraded in the oral environment, exposing unpolished, rough, inorganic filler material. The purpose of this study was to evaluate the polishing effect of two different polishing systems: One-step (PoGo) system and Sof-Lex (multistep) system on four different resin composites: Synergy D6, Clearfil APX Esthetics, Filtek Z 350 XT, Ceram X Mono. After polishing, the specimens were analyzed for average surface roughness using a two-dimensional surface profilometer. How to cite this article: Garg S, Goel M, Verma S, Mahajan N, Kaul B, Garg V. Use of "Surface Analyzer" to evaluate the Effect of Two Polishing Systems on Surface Texture of Four Newer Composites. Int J Clin Pediatr Dent 2018;11(4):266-270.

A novel approach for restoration of hemisected mandibular first molar with immediately loaded single piece BCS implant: A case report.

Mandibular first molars are the major standpoint for occlusion, and also have a wide peri-cemental area. Under specific conditions, hemisection of the tooth is indicated after an endodontic treatment. The following case report presents the hemisection of grossly carious, endodontically treated mandibular first molar, in a 23 year old female, followed by replacement of the mesial root with a single piece immediate loaded BCS (Bi-Cortical Screw) implant and a single unit porcelain fused to metal crown for the prosthetic rehabilitation of the remaining tooth structure, with the BCS implant providing strength and support to the weakened tooth structure. This procedure is an innovation in prosthetic rehabilitation of tooth structure left after hemisection and enhances the predictability of success rate of hemisection.

Novel Mannich-bases as Potential Anticonvulsants: Syntheses, Characterization and Biological Evaluation.

BACKGROUND: Mannich bases are known to be an important pharmacophore or bioactive leads in the synthesis of various potential agents that have a variety of therapeutic activities like anticancer, antipsychotic, anticonvulsant, antimalarial, anti-inflammatory, antibacterial and so forth. Thus, in the present research, conjugation of moieties like 1,5-benzoxazepines and 1,5-benzothiazepines with secondary amines like piperazine, methyl piperazine and morpholine was carried out in a Mannich base with an anticipation of good anticonvulsant activity. OBJECTIVE: Synthesis, characterization, structure activity relationship and anticonvulsant activity of the Mannich bases of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. METHODS: All the derivatives were synthesized in three steps. In the first step, substituted 4-hydroxy chalconylbenzene was synthesized by the reaction of 4-hydroxyacetophenone and substituted benzaldehyde, in the presence of potassium hydroxide. In the second step, 2,3-dihydro- 1,5- benzothiazepines and 2,3-dihydro-1,5-benzoxazepines were synthesized by the reaction of 2- thio/aminophenol with chalcones in the presence of glacial acetic acid. In the third step, these compounds finally underwent Mannich reaction with different secondary amines to the respective title compounds. All the synthesized derivatives were characterised and evaluated for anticonvulsant activity using MES (Maximal Electroshock Induced Seizure) and INH (Isoniazide Induced Convulsion) models. RESULTS: The synthesized derivatives were found to be more active in the MES model than INH model, with phenytoin and diazepam being the standards respectively. Accordingly, the mode of action of the synthesized compounds may be similar to phenytoin. The methyl piperazine containing compound, at a dose of 30 mg/kg., was found to be the most active and promising compound in the series. CONCLUSION: The benzothiazepine derivatives showed better anticonvulsant activity than the benzoxazepines derivatives.