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Aims: Our study aimed to find the incidence of fallopian canal dehiscence during surgery for cholesteatoma, to compare this incidence with a homogenous control group (otosclerosis) and to find the incidence of a labyrinthine fistula if fallopian canal dehiscence is present., Material and Methods: Prospective case control study design was used in the setting of a tertiary care referral center. Subjects included 60 patients. 30 patients diagnosed with cholesteatoma were taken as cases and 30 patients with conductive or mixed hearing loss suspected of otosclerosis were taken as controls. The method was identification of bony dehiscence under operating microscope. In case of finding of dehiscence of fallopian canal, presence of labyrinthine fistula was searched. The cases underwent modified radical mastoidectomy and controls underwent exploratory tympanotomy after giving a written informed consent. Institutional ethics committee clearance was obtained., Results: Fallopian canal dehiscence was recorded in all subjects. 50% of cases and 3.3% of controls showed presence of fallopian canal dehiscence. This correlation was statistically significant (p < 0.001). Also 26.7% cases with fallopian canal dehiscence had a semicircular canal fistula (4 out of 15),but this finding was not significant (p = 0.100)., Conclusion: From our study it was evident that there were very high chances of finding a fallopian canal dehiscence in cases of cholesteatoma than in cases undergoing exploratory tympanotomy. Also, presence of labyrinthine fistula with fallopian canal dehiscence was likely but not significant., (© Association of Otolaryngologists of India 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The objective of this study was to evaluate the efficacy and outcome using the maxillary swing approach for the management of extensive nasopharyngeal angiofibroma. A retrospective case series analysis in a tertiary care centre revealed eighteen cases with extensive nasal angiofibroma operated using the maxillary swing approach between 2011 and 2017. All patients had tumour extension to the lateral most portions of the infratemporal fossa with complete occupation and destruction of the lateral wall of the sphenoid sinus causing abutment to the cavernous sinus and complete involvement of the pterygopalatine fossa and pterygoid base. One patient displayed full occupancy of the maxillary sinus as a consequence of erosion of the posterior and medial walls of the maxillary sinus. All patients underwent tumour excision using the maxillary swing approach. Patients were followed up for a minimum period of 1 year after surgery. The maxillary swing approach gave optimal exposure of the entire central skull base including the infratemporal fossa and its extreme lateral and superior aspects. Adequate tumour exposure and vascular control could be achieved in all cases resulting in complete tumour excision. The mean operative time was 3 h 15 min. Post-operative healing was satisfactory with palatal fistula formation in four cases and all patients remaining disease-free up to the present time. One had minimal misalignment of the halves of the upper jaw and two had epiphora, of which one required dacryocystorhinostomy. The maxillary swing is an effective approach in the management of extensive nasopharyngeal angiofibroma and leads to optimal anatomical exposure with minimal morbidity., Competing Interests: Conflict of InterestThe author declare that they don’t have conflict of interest., (© Association of Otolaryngologists of India 2021.)

Fibromyxoma is a rare benign odontogenic tumor of mesenchymal origin which has a potential for a highly aggressive turnout. We present the case of a 30 year old lady who came with a slow-growing swelling in the oral cavity, which turned out to be a fibromyxoma in an unusual location-maxilla. The lesion was excised completely without any bony or soft tissue remnant and the histopathological examination confirmed the diagnosis. The rest of the course was uneventful and the patient is in follow up without any recurrence., (© Association of Otolaryngologists of India 2020.)

To study the presence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection in our set up. Longitudinal study, 1st March 2020-15th August 2020, at a tertiary care hospital. RT PCR positive for SARSCoV-2 patients, above 18 years age included. Excluding patients with previous history of changes in smell or taste sensation, severely ill at the time of admission, history of taking drugs at the time of COVID 19 infection that affect the smell or taste sensation. 435 patients included after obtaining an institutional ethical clearance. After an informed consent, these patients were followed up telephonically, to record any subjective improvement in olfactory or gustatory symptoms and an approximate duration of recovery. Olfactory and/or gustatory dysfunction 10.8% (47/435). Mean (SD) age-34.53(10.8) years. Females affected significantly more [X2 (1, N  = 435) = 7.45, p value is 0.006, significant at p  < 0.05]. Olfactory dysfunction significantly associated with gustatory dysfunction [X2 (1, n  = 435) = 182.29, p  < 0.00001]. 19.8% ( N  = 435) of individuals remained asymptomatic. Nasal symptoms rare (4%, N  = 47). Mean (SD) recovery olfactory and gustatory dysfunction 12.1 (7.7) and10.8 (6.3) days respectively. Subjective loss of smell or taste dysfunction was far less common. Women and younger population reported olfactory or gustatory dysfunction commonly. Olfactory and gustatory changes without nasal symptoms, suspicion of COVID-19 infection is relevant. Recovery is complete and early., (© Association of Otolaryngologists of India 2021.)

Background: Disease-specific human induced pluripotent stem cells (hiPSCs) can be generated directly from individuals with known disease characteristics or alternatively be modified using genome editing approaches to introduce disease causing genetic mutations to study the biological response of those mutations. The genome editing procedure in hiPSCs is still inefficient, particularly when it comes to homology directed repair (HDR) of genetic mutations or targeted transgene insertion in the genome and single cell cloning of edited cells. In addition, genome editing processes also involve additional cellular stresses such as poor cell viability and genetic stability of hiPSCs. Therefore, efficient workflows are desired to increase genome editing application to hiPSC disease models and therapeutic applications., Methods and Results: To this end, we demonstrate an efficient workflow for feeder-free single cell clone generation and expansion in both CRISPR-mediated knock-out (KO) and knock-in (KI) hiPSC lines. Using StemFlex medium and CloneR supplement in conjunction with Matrigel cell culture matrix, we show that cell viability and expansion during single-cell cloning in edited and unedited cells is significantly enhanced. Keeping all factors into account, we have successfully achieved hiPSC single-cell survival and cloning in both edited and unedited cells with rates as maximum as 70% in less than 2 weeks., Conclusion: This simplified and efficient workflow will allow for a new level of sophistication in generating hiPSC-based disease models to promote rapid advancement in basic research and also the development of novel cellular therapeutics., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

S-matrix bootstrap and positivity bounds are usually viewed as constraints on low-energy theories imposed by the requirement of a standard UV completion. By considering graviton-photon scattering in the standard model, we argue that the low-energy theory can be used to put constraints on the UV behavior of the gravitational scattering amplitudes.

β-thalassemia (BT) is a hereditary blood disorder caused by mutations in the β-globin (HBB) gene leading to severely reduced or no synthesis of the β-chain of adult hemoglobin. IVS1-5 (G > C) is the most common BT mutation in Indian population and yet no patient-specific cellular models have been generated. Here, we have established an induced pluripotent stem cell (iPSC) line, IGIBi002-A from a thalassemia patient with a homozygous IVS1-5(G > C) mutation. Characterization of IGIBi002-A demonstrated that these iPSCs are free of exogenous reprogramming genes and expressed pluripotent stem cell markers, exhibited a normal karyotype and were potential of three germ layer differentiation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients., Methods: These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP., Results: As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0-11.6) years; median follow-up time was 5.2 (range 0-10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias., Conclusions: Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab., Trial Registration Number: NCT00493298., Competing Interests: Competing interests: HB has received compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Oxford Pharmagenesis and Teva and research support from Biogen, Merck, Novartis, MS Research Australia, NHMRC Australia and the UK MS Trust. LK’s institution (University Hospital Basel) has received the following in the last 3 years and used exclusively for research support at the department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi, Santhera, Teva and Vianex, as well as royalties for Neurostatus-UHB products; the Research of the MS Centre in Basel has been supported by grants from Bayer, Biogen, Novartis, the European Union, the Roche Research Foundations, the Swiss MS Society and the Swiss National Research Foundation. HW has received honoraria from AbbVie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche, MedDay, Merck Serono, Novartis, Roche Pharma AG, Sanofi Genzyme and Teva and research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG and Sanofi Genzyme. MT has received compensation for consulting from Biogen, Merck Serono and Novartis; speaker honoraria from Biogen, Merck Serono, Novartis, Sanofi and Teva; and research grants from Biogen, Merck Serono and Novartis. TS has received honoraria for consultancy and funding for travel from Biogen and Novartis. IC, NC, P-RH and SL are employees of and may hold stock and/or stock options in Biogen. RK and SJ were employees of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sickle cell disease (SCD) is an autosomal recessive disorder caused by a mutation in β-globin (HBB) gene. We have generated an induced pluripotent stem cell (iPSC) line, IGIBi001-A from an Indian sickle cell patient with a homozygous HBB gene mutation using Sendai virus reprogramming system. Characterization of IGIBi001-A showed that these iPSCs are transgene-free and expressed pluripotent stem cell markers. They had a normal karyotype and were able to differentiate into all three germ layers. This new SCD-iPSC line will contribute to better understanding of the disease biology of sickle cell anemia and for screening of small molecule drugs., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

In this article, we describe three patients with heart failure whose 2D echocardiograms showed left ventricular non-compaction cardiomyopathy characterized by prominent trabeculation with deep intertrabecular spaces in the myocardium.