Expression of Toll-like receptors in Haemonchus Contortus resistant sheep: An innate immune parameter for host defense against gastrointestinal nematode infection.

Innate immune parameters, a first line of defense against invading pathogens like bacteria, parasites, fungi, etc, play a significant role in the prevention and elimination of aetiological agents primarily by recognition of invading pathogen-specific molecules by different pattern recognition receptors. Toll-like receptors (TLRs), a type-I transmembrane glycoprotein, cause innate immune responses mainly by produing inflammatory cytokines, chemokines and interferons. The objective of present study was to determine the role of TLRs in parasite resistance in Malpura sheep. In the current study, transcript variation of TLRs and its downstream signalling molecules namely MyD88, TRIF, IRF-3, TRAF, TGF-ß, NFκB, and CD14 were ascertained by real-time PCR in Haemonchus contortus resistant (R) and susceptible (S) Malpura sheep. Results have shown significantly (P<0.05) up-regulated expression of TLR-2, TLR-4, TLR-5, TLR-8 and TLR-10 in July however down-regulated patterns were observed in August and September in R-line sheep compared to S-line sheep. This indicates that at more or less equal parasite load, the TLR genes in R sheep produce more transcripts, but after parasite loads have increased hugely in the S line, they easily surpass the levels seen in the S line. Result suggests that transcriptional activity of the TLR genes was related to parasite load and there were differences between the lines at different infection intensities. Three-point transcript expression observation of the signalling molecules namely TRIF, IRF-3, TRAF, a similar pattern was observed in R sheep compared with S sheep.

Assessment of Physician Needs and Access to Inflammatory Bowel Disease Specialty Care Resources in a National Integrated Health System.

BACKGROUND: The barriers to providing high-quality inflammatory bowel disease (IBD) care go beyond educational needs alone to include access to IBD-related resources such as medications, laboratory testing, and multidisciplinary teams. We assessed the needs and resource constraints of physicians caring for Veterans with IBD to inform efforts to improve access to high-quality care. METHODS: We conducted a national observational survey study in July 2021 of gastroenterologists (GIs) and primary care providers (PCPs) caring for Veterans with IBD within the Veterans Health Administration with the intent of including physicians from all 18 Veterans Integrated Service Networks (VISN). We reported descriptive statistics and compared responses between gastroenterologists (GIs) and primary care providers (PCPs), practice locations, and years of experience using χ2 tests. RESULTS: Overall, 173 of 2241 eligible physicians completed the survey, representing an individual physician response rate of 7.7% and VISN response rate of 18 out of 18 (100%). We identified several areas of IBD care where GIs and PCPs reported discomfort including medication prescribing, treatment strategies, and special populations. Further, variability in access to IBD services and awareness of the availability of IBD-targeted medications and laboratory tests was common. This survey also highlights the frequency with which PCPs were identified among the highest volume IBD providers in their facility. CONCLUSIONS: Variation in GIs' and PCPs' comfort with IBD treatment and access to IBD resources is common and needs to be considered in leveraging virtual care and educational programs and managing the expansion of IBD support and resources within VA.

Modeling maize growth and nitrogen dynamics using CERES-Maize (DSSAT) under diverse nitrogen management options in a conservation agriculture-based maize-wheat system.

Agricultural field experiments are costly and time-consuming, and often struggling to capture spatial and temporal variability. Mechanistic crop growth models offer a solution to understand intricate crop-soil-weather system, aiding farm-level management decisions throughout the growing season. The objective of this study was to calibrate and the Crop Environment Resource Synthesis CERES-Maize (DSSAT v 4.8) model to simulate crop growth, yield, and nitrogen dynamics in a long-term conservation agriculture (CA) based maize system. The model was also used to investigate the relationship between, temperature, nitrate and ammoniacal concentration in soil, and nitrogen uptake by the crop. Additionally, the study explored the impact of contrasting tillage practices and fertilizer nitrogen management options on maize yields. Using field data from 2019 and 2020, the DSSAT-CERES-Maize model was calibrated for plant growth stages, leaf area index-LAI, biomass, and yield. Data from 2021 were used to evaluate the model's performance. The treatments consisted of four nitrogen management options, viz., N0 (without nitrogen), N150 (150 kg N/ha through urea), GS (Green seeker-based urea application) and USG (urea super granules @150kg N/ha) in two contrasting tillage systems, i.e., CA-based zero tillage-ZT and conventional tillage-CT. The model accurately simulated maize cultivar's anthesis and physiological maturity, with observed value falling within 5% of the model's predictions range. LAI predictions by the model aligned well with measured values (RMSE 0.57 and nRMSE 10.33%), with a 14.6% prediction error at 60 days. The simulated grain yields generally matched with measured values (with prediction error ranging from 0 to 3%), except for plots without nitrogen application, where the model overestimated yields by 9-16%. The study also demonstrated the model's ability to accurately capture soil nitrate-N levels (RMSE 12.63 kg/ha and nRMSE 12.84%). The study concludes that the DSSAT-CERES-Maize model accurately assessed the impacts of tillage and nitrogen management practices on maize crop's growth, yield, and soil nitrogen dynamics. By providing reliable simulations during the growing season, this modelling approach can facilitate better planning and more efficient resource management. Future research should focus on expanding the model's capabilities and improving its predictions further.

A Case Report on Iris Disk Positioning on a Custom-Made Ocular Prosthesis Using an Adjustable Trial Frame.

Trauma, cancer, and congenital defects may all result in the loss of an eye. This leads to significant emotional and physical challenges in an individual's life. In such cases, cautious preoperative, surgical, and prosthetic planning employing a multidisciplinary approach is essential for effective rehabilitation. Iris positioning is one of the crucial steps in the fabrication of a customized ocular prosthesis. Iris positioning is a technique-sensitive process, hence visual evaluation by itself could not provide reliable results. This case report illustrates a method of iris disk positioning on a custom-made ocular prosthesis using an adjustable trial frame. The advantage of the adjustable mechanism of the adjustable trial frame was utilized here to position the iris on the scleral blank. Since the iris disk on the ocular prosthesis was positioned in symmetry with that of the natural eye, the patient's aesthetics were restored.

Evaluation of structural and compositional changes on the root surface exposed to diode laser (810 nm): An In-vitro study.

Background: The laser therapy has been used as an adjuvant for conventional periodontal disease as they exhibit a bactericidal effect on scaling and root planning by its thermal and photo disruptive effects on the pathogens. This study focuses on the structural and compositional changes induced on the root surfaces of teeth following diode laser (DL) application with increasing quantum of exposure time. Objective: The objective of this study was to evaluate the structural and compositional changes on the root surface of extracted human permanent teeth after application of DLs (810 nm) with varying time interval. Materials and Methods: Twenty samples of single-rooted periodontally compromised extracted teeth were utilized for this study. Root planning was done and the roughness caused by the instrumentation was measured using profilometric analysis. Then, the samples were divided into four groups, with DL application time: Group 1 - laser application for 15 s, Group 2 - laser application for 30 s, Group 3 - laser application for 45 s, and Group 4 - laser application for 60 s. A scanning electron microscope was used to examine the cemental surface and energy-dispersive X-ray analysis software assesses the compositional changes of the teeth in each group. Results: This study reveals that on exposure of DL (810 nm) on the root surface when time of exposure increases, there were relative increases in surface irregularities and charring. There were significant changes in the chemical composition of the tooth surface.

Rehabilitation of an Orofacial Cleft through Presurgical Nasoalveolar Molding with a 1-year Follow-up.

Aim: To highlight the effectiveness of Presurgical Nasoalveolar Molding (PNAM) technique and the appliance used prior to the surgical reconstruction of cleft lip and palate in newborns. Background: In underdeveloped and developing countries, babies born with oral clefts, are generally anemic with low birth weight and may be unfit for surgery immediately. Feeding these babies is also difficult as the air leaks through the cleft and they cannot create the suction needed for suckling. Case description: Two newborn babies, presented with unilateral midfacial clefts involving the lip, alveolus and palate. Conclusion: The PNAM appliance enabled breast Feeding while lessening the soft tissue and cartilaginous deformity and allowing surgical soft tissue repair with minor scar formations. Clinical significance: PNAM can reduce the surgical burden and reduce the number of surgical revisions when initiated early. How to cite this article: Ferreira AN, Eswaramurthy P, Aras MA, et al. Rehabilitation of an Orofacial Cleft through Presurgical Nasoalveolar Molding with a 1-year follow-up. Int J Clin Pediatr Dent 2023;16(1):162-165.

Impact of Thymectomy on Crisis Incidence and Quality of Life amongst Generalised Myasthenia Gravis Patients.

Background: Thymectomy, combined with corticosteroids, immunosuppressive agents, and cholinesterase inhibitors, has been accepted as the standard treatment for myasthenia gravis (MG) patients. Data on the effect of thymectomy on occurrence of myasthenic crisis are few. Objectives: To assess the long-term impact of thymectomy in patients with generalized Myasthenia gravis (GMG) in terms of occurrence of myasthenia crisis and quality of life. Methods: A retrospective analysis of 274 clinical records of patients diagnosed with myasthenia gravis (MG) in Nizam's institute of medical sciences (NIMS), a tertiary level teaching hospital between January 2000 and December 2015 was done. Severity of the disease was assessed using Myasthenia Gravis Foundation of America (MGFA) classification and quantitative myasthenia gravis (QMG) score. Myasthenia crisis was diagnosed in our patients when they required ventilator assistance due to respiratory failure caused by muscle weakness (MGFA class V). Quality of life (QoL) was assessed. Results: Of 230 cases included in the final analysis, 108 (46.9%) underwent thymectomy. Posttreatment crisis occurred in 53.3% of the nonthymectomy subjects, and 25.9% of thymectomy group (P < 0.001). In multivariate logistic regression analysis, after controlling for the effect of gender, age at diagnosis and grade of the disease, the odds ratio of myasthenic crisis in people with thymectomy was 0.186.(95% CI 0.087 to 0.387, P = 0.001). No statistically significant differences were observed in quality of life scores between thymectomy and nonthymectomy groups, either before (P = 0.86) or after surgery (P = 0.939). Conclusions: The odds of myasthenia crisis was lesser in people, who underwent thymectomy even after controlling for MGFA grade and other potential confounders but no significant differences in quality of life were found with thymectomy.

Association of HLA DRB1-DQB1 Haplotypes with the Risk for Neuromyelitis Optica among South Indians.

Background: Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder, mainly characterized by severe optic neuritis, transverse myelitis and the high levels of antibodies against NMO-immunoglobulin G (IgG) or aquaporin-4 (AQP4). HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are known to play a significant role in several autoimmune diseases including NMO. The rationale of the current case-control study is to explore the association of HLA-DRB1 and HLA-DQB1 alleles with the risk of NMO and its association with the clinical and serological markers. Methods: A total of 158 samples (38 NMO cases and 120-age and ethnicity matched controls) were genotyped for the HLA-DRB1 and HLA-DQB1 alleles by using PCR-SSP method. Results: Our analysis showed significant association of HLA-DRB1*10 allele (OR 2.63, 95% CI: 1.18-5.83, p=0.02) with NMO whereas DRB1*14 showed protective role against NMO (OR 0.33: 95% CI: 0.11-0.94, p=0.043). HLA-DRB1*10 allele also showed significant association in patients with NMO-IgG positive antibody (OR 3.28: 95% CI: 1.42-7.5, p=0.006). There was no association of HLA DQB1 alleles with NMO and also with NMO-IgG antibody. Among the haplotypes groups, HLA-DRB1*10-DQB1*05 (OR 2.61, 95% CI: 1.11-6.1, p=0.03), HLA-DRB1*15-DQB1*03 (OR 4.5, 95% CI: 1.81-11.5, p=0.001) were strongly associated with the risk of NMO, whereas DRB1*14-DQB1*05 (OR 0.20, 95% CI: 0.060-0.721, p=0.008) showed negative association with NMO. Conclusion: From this study, it is concluded that the HLA-DRB1*10 and DRB1*10-DQB1*05 and HLA-DRB1*15-DQB1*03 haplotypes may influence the susceptibility to NMO among the South Indians. Additionally we found DRB1*14 allele and DRB1*14-DQB1*05 haplotype showed protective role for NMO.

Gaz Alafi: A Traditional Dessert in the Middle East With Anticancer, Immunomodulatory, and Antimicrobial Activities.

Background: From the earliest times, manna has been widely used as a tasty local sweet or folk medicine. The type of manna being investigated in the present study is called Gaz-alafi, a mixture of insect and Quercus brantii leaves secretions from oak forests in the north of Iraq and west of Iran. Methods: Aqueous and ethanol extracts were prepared as decoction. Various phytochemical tests were conducted to analyze manna composition, including total phenolic contents using the Folin-Ciocalteu method and LC-MS. Gallic acid and catechin were detected in both extracts, in addition to tiliroside presence in ethanol extract, which added more value to the phenolic content of ethanol extract. Cytotoxic activities of Gaz alafi were evaluated against breast cancer cell lines and compared to normal cell lines and doxorubicin using the MTT assay. Antimicrobial properties were assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Candida albicans using the dilution method of the micro-titer plate. Serum levels of IFN-γ, interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) were measured using ELISA. The effect of extracts on splenocyte proliferation was evaluated using the lymphocytes proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay, whereas pinocytosis was evaluated using the neutral red uptake assay. Ten days after tumor inoculation, changes in tumor size, survival rates, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured. Results: The growth of cancer cells was inhibited by Gaz alafi ethanol extract. An alteration in IFN- γ, IL-2, and IL-4 levels toward antiproliferation immune response were reported for both extracts. The aqueous extract efficiently stimulated lymphocyte proliferation, phagocytosis, and pinocytosis, followed by the ethanol extracts with moderate activity. After treating the mice with ethanol extracts, a significant reduction in tumor size and several undetected tumors were recorded. Conclusions: Gaz alafi extracts (aqueous and ethanol) are promising sources for anticancer and immunostimulatory agents. Further studies are needed to fully identify the chemical composition of Gaz alafi extracts.

The Bethesda System for reporting cervical cytology.

The seminal observations of Dr. George Papanicolaou have grown, through the untiring efforts of many authors, into a universally accepted format of cytology reporting. This has helped immensely to improve the understanding of pathogenesis of cervical cancer. The insights into the complexity of interaction of the etiological and the host factors have further helped in reframing of the reporting system. The Bethesda System (TBS) stands out as a model of standardized reporting in cervicovaginal cytology. Apart from its reproducibility, it reflects the most current understanding of cervical cancer. The most important feature is its clinical relevance. Each category of this classification has clear clinical implications, which are based on solid evidence and worldwide consensus. Moreover, the authors have tried to keep it updated through continuous revisions, incorporating the technological and scientific advances. The component of specimen adequacy reflects the importance it has given to the quality assurance of the laboratory preparation. The minimization of categories, simple terminology, and the supporting image atlas - both in the print form and the web-based form, have made TBS an exemplary teaching-learning resource. The wide accessibility of TBS has been the most important factor in being adopted by a majority of pathology community all over the world.

Total knee arthroplasty in valgus knee deformity: is it still a challenge in 2021?

Total knee arthroplasty in valgus knee deformities continues to be a challenge for a surgeon. Approximately 10% of patients who undergo total knee arthroplasty have a valgus deformity. While performing total knee arthroplasty in a severe valgus knee, one should aware with the technical aspects of surgical exposure, bone cuts of the distal femur and proximal tibia, medial and lateral ligament balancing, flexion and extension gap balancing, creating an appropriate tibiofemoral joint line, balancing the patellofemoral joint, preserving peroneal nerve function, and selection of the implant regarding constraint. Restoration of neutral mechanical axis and correct ligament balance are important factors for stability and longevity of the prosthesis and for good functional outcome. Thus, our review aims to provide step by step comprehensive knowledge about different surgical techniques for the correction of severe valgus deformity in total knee arthroplasty.

Sporadic Inclusion Body Myositis: A Clinicopathological Study.

BACKGROUND: Sporadic inclusion body myositis (s-IBM) is rare in India. AIM: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011. MATERIALS AND METHODS: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed. RESULTS: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1-5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57-2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies. CONCLUSIONS: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.

The Effect of Dual Tasking and Deep Brain Stimulation Frequency Parameters on Gait in Advanced Parkinson's Disease.

OBJECTIVE: To study the effect of dual tasking and deep brain stimulation frequency parameters on gait in advanced Parkinson's disease. MATERIALS AND METHODS: This is an open label interventional study evaluating 40 post STN-DBS patients with gait disturbances. All patients were diagnosed as PD by a movement disorder specialist using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria. Patients underwent bilateral subthalamic deep brain stimulation by a qualified neurosurgeon. Patients were managed on a combination of dopamine replacement therapy as well as deep brain stimulation. Patients were assessed by stand walk sit (SWS) test for a 5 meter distance and FOG scoring during medication 'ON' state and device "ON" state, at four frequencies 180, 130, 90, 60 HZ and device "OFF" state. RESULTS: Out of 40 patients, 38 patients showed a significant improvement in gait at a single frequency (best response frequency) which is different for each patient. The mean FOG score showed significant improvement at all stimulation frequencies when compared to OFF stimulation (P < 0.05). The mean number of steps was 18.9 at best response frequency and 21.48 at 130 Hz (P < 0.0001). Number of freezing episodes also were significantly less with best frequency when compared to 130 Hz stimulation (0.28 and 0.65 respectively, (P < 0.0001). The mean FOG score was 6.45 at best frequency and 9.48 at 130 Hz (P < 0.0001). Mean Dual tasking score was 3.53 at best frequency and 5.15 at 130 Hz (P < 0.0002). CONCLUSION: Optimization of frequency setting for each patient can improve gait and that each patient may have a different optimal frequency.

Clinicoradiological Profile of Superficial Middle Cerebral Vein Thrombosis.

BACKGROUND: The diagnosis of isolated cortical vein thrombosis (ICVT) involving superficial middle cerebral vein (SMCV) remains challenging even in the present era of modern MRI protocols. OBJECTIVE: The purpose of this study is to review the clinical and radiological characteristics of SMCV thrombosis in our hospital. METHODS: Chart review of cases of SMCV thrombosis admitted in a tertiary care university hospital in South India during a 1-year period from September 2015 to August 2016. RESULTS: Five SMCV thrombosis patients were identified and presented with focal seizures. Neuroimaging showed edema (with or without hemorrhage) of cortex and white matter of inferior frontal gyrus, temporal pole, superior temporal gyrus, insular cortex, and external capsule. The thrombosis of SMCV was demonstrated by Spin echo T1-weighted, GRE-weighted axial, and postcontrast T1-weighted images in coronal and sagittal planes, with a slice thickness of <3 mm. Four received anticoagulation and all improved rapidly and completely. CONCLUSION: SMCV thrombosis should be considered in patients having recent onset seizures in appropriate setting based on MRI evidence of parenchymal edema and/or hemorrhage in the perisylvian region along with evidence of thrombosed vein in that region. Appropriate imaging sequences help in confirmation of diagnosis.

Functional Outcome of Bilateral Subthalamic Nucleus-Deep Brain Stimulation in Advanced Parkinson's Disease Patients: A Prospective Study.

BACKGROUND: Deep brain stimulation (DBS) is an accepted modality of treatment in patients with Parkinson's disease (PD). Although DBS was approved in advanced PD, it is being done in early PD as well. It was mainly developed to help the patients of PD to overcome the adverse motor effects associated with treatment and treatment failure. OBJECTIVE: The objective is to study the efficacy of subthalamic nucleus (STN)-DBS procedure in patients with PD. MATERIALS AND METHODS: This was a prospective, single-center, follow-up observational study using a direct, structured interview of 40 selected PD patients. Preoperative assessment using Unified PD Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MOCA), and Parkinson's Disease Questionnaire-39 were done. All the patients underwent DBS. Postoperatively, similar assessment was done during follow-up period of 6 months. The results were analyzed using Student's t-test. RESULTS: The total score of UPDRS-III was reduced by 35% after STN-DBS intervention which was statistically significant (P < 0.05). STN-DBS intervention was successful in significantly reducing all UPDRS-III subscores but failed to reduce the scores in case of postural stability. MOCA scores of the patients were not found to be affected by STN-DBS intervention (P = 0.1466). Similar findings were also observed for MOCA subscores, but there was significant improvement of verbal fluency in all patients. Quality of life(QoL) improved significantly in all patients after STN-DBS intervention in all areas. Lower baseline UPDRS-III scores were found to enhance the QoL both in "off" and "on" state. However, prolonged disease duration and older age at PD onset were found to be hampering factors in the improvement of QoL. CONCLUSIONS: STN-DBS is a safe procedure and can be performed in all patients of PD who develop disabling motor fluctuations to improve their QoL irrespective early or advanced disease.

Serum B12, Homocysteine Levels, and their Effect on Peripheral Neuropathy in Parkinson's Disease: Indian Cohort.

BACKGROUND: Cobalamin deficiency, either due to dietary inadequacy or increased consumption attributable to levodopa-mediated metabolic disturbance, and resultant hyperhomocysteinemia may contribute to peripheral neuropathy (PN) in Parkinson's disease (PD). AIM: The aim of the study is to assess the prevalence of Vitamin B12 deficiency, hyperhomocysteinemia in Indian PD patients, and their association with PN. MATERIALS AND METHODS: Clinical details were collected in 93 patients over a period of 2 years. Seventy controls were included in the study. Serum B12, homocysteine, folate, electroneurography, and autonomic function tests were done. The prevalence of B12 deficiency and hyperhomocysteinemia in PD patients and controls was assessed. The association of B12 and homocysteine levels with patients' age, disease duration, levodopa equivalent daily dose, cumulative levodopa dose, Unified Parkinson's Disease Rating Scale-III off score, modified Hoehn and Yahr score, and presence or absence of PN was studied. RESULTS: Serum B12, homocysteine levels, prevalence of B12 deficiency, and hyperhomocysteinemia were no different between cases and controls. Seven of 93 (9.68%) PD patients had PN. The median values of serum B12, folate, and homocysteine levels across patients with or without PN could not be compared as only seven of our patients had PN. CONCLUSION: The prevalence of B12 deficiency, hyperhomocysteinemia, and incidence of PN among our patients is very less when compared to the Western population. The conjecture that PN in PD patients may be secondary to B12 deficiency/hyperhomocysteinemia stands as a speculation.

Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents.

We designed a series of substituted flavones and aurones as non-competitive H1N1 neuraminidase (NA) inhibitors and anti-influenza agents. The molecular docking studies showed that the designed flavones and aurones occupied 150-cavity and 430-cavity of H1N1-NA. We then synthesized these compounds and evaluated these for cytotoxicity, reduction in H1N1 virus yield, H1N1-NA inhibition and kinetics of inhibition. The virus yield reduction assay and H1N1-NA inhibition assay demonstrated that the compound 1f (4-methoxyflavone) had the lowest EC50 of 9.36 nM and IC50 of 8.74 µM respectively. Moreover, kinetic studies illustrated that compounds 1f and 2f had non-competitive inhibition mechanism.

Validation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorders in a cohort of South Indian patients.

BACKGROUND: Neuromyelitis Optica spectrum disorders (NMOSD) are one of the most common CNS demyelinating disorders as they will present with disabling recurrent demyelinating attacks. Hence, it is of paramount importance to diagnose early, and early diagnoses and intervention will prevent further relapses associated with NMOSD. New international consensus criteria have been proposed and studies validating its application towards diagnoses of NMOSD in south Asian population are meagre. Hence we validated the proposed International Panel for NMO Diagnosis (IPND), 2015 criteria to study the clinical, demographic profile and sero-status of patients who are presenting with core clinical symptoms of NMOSD in South India and compare it with 2006 criteria. METHODS: A retrospective study was conducted in a tertiary hospital for a period of one year. Patients who had at least one core clinical feature of NMOSD were included. Demographics and clinical data were recorded and analysed. Cases were evaluated using 2015 IPND and 2006 criteria for all patients, data was analysed using SPSS. RESULTS: A total of 110 patients were included and 91(82.72%) patients fulfilled IPND 2015 criteria. Out of 91 patients, 70 patients were AQP4 antibody positive and 21 were negative. Out of 110, only 30 (27.2%) satisfied 2006 criteria (24 or 80% were seropositive). 2015 criteria were more sensitive in identifying 61 new NMOSD cases juxtaposed to 2006 criteria, this difference was statistically significant (P<0.05). CONCLUSION: The 2015 IPND criteria were more sensitive and specific than previous 2006 criteria as it covered diverse clinical manifestations of NMOSD. Applying this criteria, NMOSD could be diagnosed among patients with monophasic illness, isolated recurrent optic neuritis, isolated recurrent myelitis, cerebral syndrome, diencephalic syndrome, brainstem syndrome and area postrema syndrome, thus improving the diagnostic yield.

Molecular and Histopathological Characterization of Patients Presenting with the Duchenne Muscular Dystrophy Phenotype in a Tertiary Care Center in Southern India.

OBJECTIVE: To study the histopathological characteristics and mutation spectrum of patients presenting with the Duchenne muscular dystrophy (DMD) phenotype. METHODS: This was a descriptive study conducted over a period of 8 years. Multiplex ligation-dependent probe amplification (MLPA) was done in patients presenting with the DMD phenotype. If MLPA was negative, patients were offered muscle biopsy for histopathological studies and/or next generation sequencing (NGS) based multigene panel testing for muscular dystrophies. RESULTS: Of the 510 patients included, mutation in the DMD gene was detected by MLPA in 372 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonic duplications. Exons 45-55 were most commonly involved in large deletions and exons 1-10 were the commonest exons involved in duplications. In the MLPA-negative cohort, 27 proceeded for muscle biopsy. NGS was done in 14 patients, 10 of whom had pathogenic mutations in the DMD gene, 3 were non dystrophinopathies and no pathogenic variant could be identified in one patient. CONCLUSIONS: For patients presenting with the DMD phenotype, MLPA of the DMD gene has a high diagnostic rate of about 73%, and non-dystrophinopathies may constitute a small but significant proportion.