Development of Digit in Noise Test in Hindi.

BACKGROUND: The digit in the noise test is a simple hearing screening tool that can identify hearing loss at the early stage. This screening tool takes less time than traditional pure-tone audiometry. There is a scarcity of hearing health professionals with few resources for carrying out hearing screening on a large scale in India. Hence, a hearing screening tool for the Hindi-speaking population is needed. AIM AND OBJECTIVE: The study aimed to develop and validate the Digit in Noise test in Hindi (DIN-H). METHODS: A native Hindi female speaker recorded single digits from 1 to 9 made into triplet combinations, which were binaurally presented to 20 normal hearing subjects having hearing thresholds less than 25 dBHL from 250 to 8000 Hz in the presence of broadband speech-shaped noise. The digit triplets were homogenized using speech intelligibility function for similar difficulty levels across stimuli. The homogenized stimuli were evaluated by obtaining the Speech Recognition Threshold (SRT) of 20 normal hearing subjects. RESULTS: The Mean SRT was - 10.4 and - 11.3 dB before and after homogenization. A strong positive correlation existed between test and retest SRTs (0.78). Mean SRT and slope obtained before and after optimization were comparable to other languages like Korean and English. This test can act as a reliable screening tool for assessing individuals. The test was administered to 106 normal hearing participants. The 95th percentile of the SRT value obtained was - 5.6 dB, which was kept as a cut-off score for the screening test. CONCLUSION: DIN-H can be used as a screening tool for assessing the integrity of the auditory system on a large scale in less time for the Hindi-speaking population.

Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination.

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker Dlc1 in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.

Failure of Autophagy in Pompe Disease.

Autophagy is an evolutionarily conserved lysosome-dependent degradation of cytoplasmic constituents. The system operates as a critical cellular pro-survival mechanism in response to nutrient deprivation and a variety of stress conditions. On top of that, autophagy is involved in maintaining cellular homeostasis through selective elimination of worn-out or damaged proteins and organelles. The autophagic pathway is largely responsible for the delivery of cytosolic glycogen to the lysosome where it is degraded to glucose via acid α-glucosidase. Although the physiological role of lysosomal glycogenolysis is not fully understood, its significance is highlighted by the manifestations of Pompe disease, which is caused by a deficiency of this lysosomal enzyme. Pompe disease is a severe lysosomal glycogen storage disorder that affects skeletal and cardiac muscles most. In this review, we discuss the basics of autophagy and describe its involvement in the pathogenesis of muscle damage in Pompe disease. Finally, we outline how autophagic pathology in the diseased muscles can be used as a tool to fast track the efficacy of therapeutic interventions.

Fabrication of orbital prosthesis by two different methods in patients with post-COVID-19 rhino-orbital maxillary mucormycosis: A case series.

Neoplasms, congenital disorders, fungal infections, and traumatic injuries are the predominant causes of orbital defects. Various retentive mechanisms such as application of adhesive, utilization of mechanical undercuts, and implant-supported attachments are generally used in the maxillofacial prosthesis. In the orbital region, the result of magnet-retained attachments is favorable compared with other mechanisms. Different advantages of the magnet-retained prosthesis are less manual dexterity needed during insertion or removal and better maintenance of hygiene. The skin-implant interface and thick tissues in the maxillofacial region are the critically important points that should be given importance during the planning and placement of implants. Ideally, implant sites for orbital prosthesis are the lateral, infra-, and supraorbital rims of the orbital region. The following case series describes two different methods to rehabilitate patients with an exenterated eye due to mucormycosis by individually designed implant with magnetic attachment and mechanical undercut-retained orbital prosthesis.

The immediate impact of mandatory helmet law on maxillo-facial trauma: A comparative study in a major trauma center, Uttar Pradesh.

Aim: To analyze the effect of the mandatory helmet rule in helmet usage among motorcycle riders and on facial trauma and to determine the significance of difference in the possibility of facial trauma between the helmeted and non-helmeted motorcycle riders. Setting and Design: A retrospective comparative study conducted in a major trauma center at Uttar Pradesh. Material and Method: Data for the present study was obtained from records of the Emergency Department of Trauma Center, for a period of two months before and after the implementation of The Motor Vehicles Act in UP. The study included patients with a history of non-fatal motorcycle accidents who sustained facial injuries regardless of the presence of injuries to other areas of the body during the study period. Information regarding helmet usage during the accident was also recorded. The results were compared between the pre-law period and post-law period. Statistical Analysis Used: Sample t-test was applied to find the level of significance. Results: Out of 219 injured patients, 152 (69.40%) subjects were not wearing helmets, whereas only 67 (30.59%) subjects were wearing helmets. It was observed that around 68.18% of people stated wearing helmets after law implementation with a statistical significance (P value < 0.05). Conclusion: Our study shows that the mandatory helmet rule with elevated penalty rates has significantly increased the usage of helmet among the motorcycle riders, and it also proves that the possibility of facial trauma is significantly higher in non-helmeted riders when compared to helmeted riders.

Pilot Evaluation of Perioperative High Dose Rate Brachytherapy in Head Neck Cancers.

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

Metformin-Induced Chronic Diarrhea Misdiagnosed as Irritable Bowel Syndrome for Years.

Metformin is the most prescribed and recommended drug for type 2 diabetes mellitus because of its better tolerability, pleiotropic benefits, and cost-effectiveness. Metformin inhibits hepatic glucose production and increases muscle glucose uptake. Metformin is also associated with gastrointestinal side effects like abdominal bloating, flatulence, diarrhea, nausea, and vomiting. Metformin-related gastrointestinal side effects are mainly due to alteration in gut microbiota, raised intestinal glucose, and increased ileal bile salt reabsorption. We report a case of a 62-year-old diabetic patient who presented with chronic diarrhea with a weight loss of 6 kg from the last six years after initiation of metformin. He underwent multiple investigations and was finally misdiagnosed with irritable bowel syndrome for years. After discontinuation of metformin, there was a significant improvement in gastrointestinal symptoms. Our case highlights the importance of metformin-induced chronic diarrhea if no other causes for the diarrhea are obvious in patients with type 2 diabetes taking metformin. Consideration of this potential side effect of metformin must be valuable to avoid unwarranted investigations, additional drug therapy, and annoyance of the patients.

Assessment of Shame and Stigma in Head and Neck Cancer: A Meta-Analysis.

Background: Head and neck cancer is the most common cancer around the globe, following lung cancer and breast cancer. Treatment at advanced stages of head and neck cancer is usually followed intense surgical procedures, which leads to mutilation among patients. Mutilation imparts a sense of disgrace and causes a feeling of shame and stigma in the patient. The feeling of shame and stigma persists over time and affects the overall long-term survival of patients by deteriorating their quality of life. Objectives: Since shame and stigma is an important psychological domain of head and neck cancer, the present article aims toward evaluating the studies published so far for the assessment of shame and stigma in head and neck cancer and highlighting the lacunae in the existing research designs. The present study also aims to design a checklist that could be followed while developing, translating, or validating a psychometric instrument that aims to measure shame and stigma in head and neck cancer. Methods: In the present metanalysis, all articles published in the past years on shame and stigma in head and neck cancer was compiled using a predefined data extraction matrix. The available literature was compiled for major objectives of the study, the sample size used, major findings, and critical lacunae that need to be addressed. Results: Shame and stigma is a very important domain of psychological well-being in head and neck cancer patients, which yet not appropriately addressed and further need to be researched. Conclusion: Future studies could be based on the lacunae highlighted in the existing literature, and the prescribed methodology checklist could be taken into consideration while conducting further studies involving developing, translating, or validating a psychometric instrument related to shame and stigma in the head and neck cancer.

Development of HPLC Method for Ixabepilone (Oncology Drug) in Bulk and Dosage Form: Quantification of Impurities and Forced Degradation Studies.

The objective of study is to develop a new stability-indicating HPLC method for quantifying ixabepilone degradation products and known process impurities (EPO-2 and Epothilone B) in bulk and injectable dose forms. A gradient stability-indicating RP-HPLC approach was developed to determine the known impurities of ixabepilone in ixabepilone API and ixabepilone for injection. Ixabepilone was subjected to base, acid, oxidation, photolytic and thermal degradations. The gradient approach was used to optimize the mobile phase-A [pH 4.8 acetate buffer (10 mM) and acetonitrile 90:10 v/v] and mobile phase-B [pH 4.8 acetate buffer (10 mM) and acetonitrile 20:80 v/v] of a USP L1 column. A wavelength of 250 nm was chosen based on known impurities and degradation products response, with a 1.0 mL/min flow rate. In compliance with ICH criteria Q2(R1), the developed technique was validated. The stability-indicating-related impurities technique was proven to be appropriate for estimating degrading impurities and known impurities in ixabepilone API and ixabepilone injection.

Reply to the 'Comment on "CO2 as oxidant: an unusual light-assisted catalyst free oxidation of aldehydes to acids under mild conditions"' by S. R. Khan, S. Saini, K. Naresh, A. Kumari, V. Aniya, P. K. Khatri, A. Ray and S. L. Jain, Chem. Commun., 2022, 58, 2208.

Our recent Communication (S. R. Khan et al., Chem. Commun., 2022, 58, 2208) suggested that CO2 can be used as a potential oxidant under light irradiation without using any catalyst for the oxidation of aldehydes to acids at room temperature. The Comment based on the published literature on the catalytic oxidation of aromatic aldehydes by CO2 and thermodynamical data argued on the realism of the experimental data.

Association of Cochlear Implant Management Skills of Parents and Outcomes in Their Cochlear Implanted Wards: An Indian Perspective.

Parental involvement in the rehabilitation process is one of the critical factors for the success of cochlear implants in their wards. Skills to use a cochlear implant (CI) device appropriately and manipulate the different settings are essential to gain maximum benefits. There was a need to have a tool in Hindi to assess the skills of parents to manage the CI device. The study was conducted with the following aims: To translate and adapt Self-administered Cochlear Implant Management Skills (CIMSSelf) into the Hindi language. To find an association between the CI management skills of parents and outcomes in their implanted wards. To compare pre-post retraining scores on CIMS-self in Hindi (HN) and to find out factors affecting the scores. CIMS-self (English) was translated into Hindi using the forward and backward translation method. CIMS-self (HN) was administered to 22 parents of cochlear implanted children to evaluate their CI device management skills in the pretraining phase. The questionnaire was re-administered between 2 and 4 weeks to check the reliability. The outcome of CI in the children was assessed using the test tools viz. Categories of Auditory Perception, Integrated Scales of Development, Speech Intelligibility Rating, and Meaningful Auditory Integration Scale (MAIS). Subjects with less than 100% score received retraining on CI device management skills. CIMS-self (HN) was readministered two weeks after completing training, and results were compared between pre-post training sessions. There was no significant correlation between CIMS-self (HN) scores and demographic of the parents and their implanted wards, CI device factors, and clinical outcomes. A significant correlation was found between the CIMS-self (HN) and MAIS scores (p < .05). The Cronbach's alpha for test-retest reliability of the CIMS-self (HN) survey was 0.998. Participants showed a significant improvement in CIMS-self (HN) scores following the intervention, demonstrating that the CIMS-self (HN) is sensitive enough to detect changes in CI device management following retraining. A client who self-reports difficulty may benefit from consultation if it helps to improve their confidence in CI device management. The CIMS-self (HN) survey can be used to evaluate and re-evaluate CI device management skills at regular intervals and may save clinical time.

Management and outcome of locally advanced oral squamous cell carcinoma.

Management of locally advanced OSCC is multimodal. No single therapy has been proved to be efficacious. However there is a trend towards surgical intervention in operable disease. In this review we appraise the various therapies used for the management of locally advanced OSCC. We review the literature with regards to the various treatment options for locally advanced OSCC. We categorically divided the manuscript into resectable, unresectable and technically unresectable disease. Surgery is the ideal treatment modality for resectable disease. For unresectable disease concurrent chemoradiation appears to improve survival compared to radiotherapy alone. Induction therapy might downstage tumors in the unresectable category. Targeted and Immunotherapy is reserved for recurrent, metastatic or platinum refractory OSCC. Management of locally advanced OSCC is multimodal with surgery playing the primary role. In the event where the tumor is in operable concurrent chemoradiotherapy is regarded as the best treatment modality. Induction chemotherapy currently cannot be recommended for resectable or even unresectable oral squamous cell carcinomas. However for technically unresectable disease it might play a role in improving respectability but it depends on the response of the tumor. Targeted therapy and immunotherapy is currently used for recurrent, metastatic and/or platinum refractory Head and Neck cancers. Currently it is not recommended for initial management of locally advanced disease.

Postauricular Transcanal Posterior Tympanectomy (PT2) Approach - A Modified Surgical Technique for Jugulotympanic Paragangliomas

Abstract Introduction The surgical management of jugulotympanic paragangliomas has remained challenging. They are the second most common type of tumor of the temporal bone after acoustic neuroma. It has been noticed by the authors that the jugulotympanic paragangliomas may have extensions to the epitympanum and aditus in addition to the mesotympanum and hypotympanum. The modified technique could be an alternative to the conventional facial recess technique for complete removal of the tumors. Objective To highlight the modified surgical technique for the surgical treatment of jugulotympanic paragangliomas. Methods This is a retrospective review of 34 cases of jugulotympanic paragangliomas treated in a tertiary center with respect to clinical presentation, diagnosis, and surgical treatment. Tinnitus and hearing loss were predominant symptoms. A modified technique of postauricular transcanal posterior tympanectomy with extended hypo-tympanic access was performed in 29 patients. Only two cases were operated with a classical transcanal approach. A canal wall down the mastoidectomy was required in three patients. Results The patients operated on with the modified technique had complete excision evident by absence of any lesion in computed tomography and the disappearance of tinnitus. However, two patients had recurrence of symptoms and presence of tumor in the follow-up period. These two patients underwent revision surgery. None of the patients required postoperative radiotherapy or gamma knife therapy. Conclusions Jugulotympanic paragangliomas can be effectively managed with the modified technique to ensure complete removal of the lesions. This technique has not been reported earlier in the literature.

Postauricular Transcanal Posterior Tympanectomy (PT 2 ) Approach - A Modified Surgical Technique for Jugulotympanic Paragangliomas.

Introduction The surgical management of jugulotympanic paragangliomas has remained challenging. They are the second most common type of tumor of the temporal bone after acoustic neuroma. It has been noticed by the authors that the jugulotympanic paragangliomas may have extensions to the epitympanum and aditus in addition to the mesotympanum and hypotympanum. The modified technique could be an alternative to the conventional facial recess technique for complete removal of the tumors. Objective To highlight the modified surgical technique for the surgical treatment of jugulotympanic paragangliomas. Methods This is a retrospective review of 34 cases of jugulotympanic paragangliomas treated in a tertiary center with respect to clinical presentation, diagnosis, and surgical treatment. Tinnitus and hearing loss were predominant symptoms. A modified technique of postauricular transcanal posterior tympanectomy with extended hypotympanic access was performed in 29 patients. Only two cases were operated with a classical transcanal approach. A canal wall down the mastoidectomy was required in three patients. Results The patients operated on with the modified technique had complete excision evident by absence of any lesion in computed tomography and the disappearance of tinnitus. However, two patients had recurrence of symptoms and presence of tumor in the follow-up period. These two patients underwent revision surgery. None of the patients required postoperative radiotherapy or gamma knife therapy. Conclusions Jugulotympanic paragangliomas can be effectively managed with the modified technique to ensure complete removal of the lesions. This technique has not been reported earlier in the literature.

Scoparone chemical modification into semi-synthetic analogues featuring 3-substitution for their anti-inflammatory activity.

Natural products (NPs) continue to serve as a structural model for the development of new bioactive molecules and improve the process of identifying novel medicines. The biological effects of coumarins, one of the most researched compounds among NPs, are currently being thoroughly investigated. In the present investigation, we reported the synthesis of nineteen semi-synthetic 3-substituted scoparone analogues, followed by their characterization using analytical methods such as NMR, HPLC, and HRMS. All compounds screened for in vitro and in vivo study for their ability to reduce inflammation. The SAR study worked effectively for this particular scoparone 3-substitution, as compounds 3, 4, 9, 16, 18, and 20 displayed improved in vitro results for TNF-α than the parent molecule. Similarly, compounds 3, and 17 showed a higher percentage of IL-6 inhibition. Compounds 3, 4, and 12 have also been identified by in vivo studies as promising candidates with higher percent inhibition than the parent scoparone molecule. As evident from all in vitro and in vivo studies, compound 3 showed the most potent anti-inflammatory activity among all.