Nobiletin regulates intracellular Ca2+ levels via IP3R and ameliorates neuroinflammation in Aß42-induced astrocytes.

Astrocytes are the major glial cells in the human brain and provide crucial metabolic and trophic support to neurons. The amyloid-ß peptide (Aß) alter the morphological and functional properties of astrocytes and induce inflammation and calcium dysregulation, contributing to Alzheimer's disease (AD) pathology. Recent studies highlight the role of Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in inflammation. Reactive oxygen species (ROS) generated due to Aß, induce apoptosis in the brain cells worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 and P2Y2), metabotropic glutamate receptor (mGLUR)5, α7 nicotinic acetylcholine receptor (α7nAChR), and N-methyl-d-aspartate receptors (NMDARs), have been suggested to interact with inositol trisphosphate receptor (IP3R) on the endoplasmic reticulum (ER) to induce Ca2+ movement from ER to cytoplasm, causing Ca2+ dysregulation. We found that the citrus flavonoid nobiletin (NOB) protected primary astrocytes from Aß42-induced cytotoxicity and inhibited TLR4/NF-κB signaling in Aß42-induced primary rat astrocytes. NOB was found to regulate Aß42-induced ROS levels through Keap1-Nrf2 pathway. The receptors P2Y1, P2Y2, mGLUR5, α7nAChR, and NMDARs induced intracellular Ca2+ levels by activating IP3R and NOB regulated them, thereby regulating intracellular Ca2+ levels. Molecular docking analysis revealed a possible interaction between NOB and IP3R in IP3R regulation. Furthermore, RNA sequencing revealed various NOB-mediated biological signaling pathways, such as the AD-presenilin, AD-amyloid secretase, and Wnt signaling pathway, suggesting possible neuroprotective roles of NOB. To conclude, NOB is a promising therapeutic agent for AD and works by modulating AD pathology at various levels in Aß42-induced primary rat astrocytes.

Empirical overview of a delayed diagnosis of bilateral congenital choanal atresia in an adolescent male: management with 'coblation-assisted surgery'.

Bilateral choanal atresia (CA) is a congenital anomaly consisting of an imperforated choana that leads to newborn fatalities but, if unilateral, may go unnoticed for many years. Bilateral CA occurring without significant symptoms and remaining undiagnosed for many years is rare. This case report identifies an adolescent male with bilateral CA who remained undiagnosed till adolescence. The patient presented with isolated complaints of chronic nasal obstruction and discharge and was diagnosed with bilateral CA by endoscopic and radiological evaluation. The patient underwent a coblation-assisted endoscopic CA repair, with a crossover mucoperiosteal flap technique, without stenting and with a successful outcome.

Revisiting the Predictive Factors for Nodal Metastasis in Oral Cancers-a Leap Towards Personalized Patient Treatment Approach.

The incidence of oral squamous cell carcinoma is steadily increasing globally, and even with a better understanding of tumor biology and advanced treatment modalities, the survival of OSCC patients is still not improved. A single metastatic cervical node can decrease survival by 50%. Our study intends to identify the clinical, radiological, and histological factors, significant for nodal metastasis in the pretreatment setting. Ninety-three patients' data is prospectively collected and analyzed to identify the significance of various factors in predicting nodal metastasis. Clinical factors like smokeless tobacco and nodal characteristics and T category and radiological factors like the number of specific nodes were significant for pathological nodes on univariate analysis. Ankyloglossia, radiological ENE, and radiological nodal size were significant on multivariate analysis also. In the pretreatment setting, clinicopathological and radiological factors can be used to predict nodal metastasis in generating predictive nomograms and for better planning of treatment.

Microscopic Parotidectomy: A Prospective Study.

To assess the parameters' setting of the microscope during parotidectomy and the impact of microscopic parotidectomy on facial nerve functional status. A prospective study was conducted on 28 patients in a tertiary care center, who underwent microscopic parotidectomy. Microscope's settings' like magnification, focal length, diameter of the visualized field, and clock position were recorded. Facial nerve functional status was also recorded. All surgeries were performed by right-handed surgeons using Leica F 20 M525 microscope. Clock position of microscope for right parotidectomy ranged between 7 and 10 o clock and for left, it ranged between 7 and 12 o clock. Magnification ranged between 1.3 × and 3.2 ×; magnifications of 1.3 × and 1.8 × were preferred from incision to separation of parotid from sternocleidomastoid muscle, 1.8 × and 2 × for dissection of the facial nerve trunk, and 2 × and 3.2 × for individual branches of the facial nerve. Focal length ranged between 251 and 410 mm and the diameter of the visualized field ranged between 7 and 14.7 cm. Out of 24 cases of benign lesions, 2 (8.3%) developed facial paresis which resolved in 3 months. Two out of four cases of malignancy developed permanent palsy as nerve branches were sacrificed to achieve tumor clearance. Using a microscope for parotidectomy is advantageous for facial nerve dissection, reducing chances of facial paralysis. The microscope was also found to be useful for teaching. The use of appropriate microscopic parameters avoids the glitch of transition from open to microscopic approach.

The Impact of Unilateral Sensorineural Hearing Loss on Quality of Life of Sub-Himalayan Population.

Introduction: Unilateral Sensorineural Hearing Loss (USNHL) is an age-old known entity. Patients with USNHL lack the merits of binaural hearing, i.e., temporal summation, sound localization, and speech recognition in a noisy environment. The lack of binaural hearing affects such individuals' quality of life (QOL). The present study is the most extensive Indian series related to QOL in USNHL patients. Objectives: This study aims to assess the impact of USNHL on the QOL of patients in the state of Uttarakhand. Methods: A cross-sectional study was carried out at a tertiary care center in Uttarakhand over a period of 18 months, from January 2018 to July 2019. A total of 115 patients with pure USNHL were evaluated using a validated questionnaire-Hearing Handicap Inventory for Adults-Hindi (HHIA-H). Results: In our study, patients with higher HHIA-H scores were male, young adults (age group 18-30 years), students, and laborers. Most of our patients (64%) had significant handicaps, followed by moderate handicaps in 25%. However, no significant correlation of degree of handicap was seen with age, duration, and degree of hearing loss. Conclusion: USNHL can lead to a significant handicap that can severely affect the emotional and social aspects of life. Thus, early diagnosis and rehabilitation are essential to prevent handicap and uplift QOL in patients with USNHL. This trial is registered with Clinical Trials Registry of India (CTRI reg. no. CTRI/2018/06/014396).

Role of Blood Investigations in Idiopathic Unilateral Sensorineural Hearing Loss.

Majority of unilateral sensorineural hearing loss are idiopathic. Hence, outcome depends on factors which are associated with nature of disease and its treatment. These can be sudden or progressive. Various studies are done to evaluate the association in sudden variety, however causality still lacks evidence. There are limited studies regarding progressive variety and its outcome. A prospective study of 40 patients with idiopathic unilateral SNHL was carried out which attempts at identifying factors associated with either disease severity or its prognosis. A significant association was seen between distribution of random blood sugar and post treatment improvement in patients with sudden USNHL (p = 0.045). No significant association was seen with other blood parameters to treatment outcome in sudden SNHL, and severity of progressive SNHL to any blood parameters. Elevated blood sugar may affect a negative effect on treatment outcome in unilateral ISSNHL. There is scarcity of evidence in scientific literature related to "Unilateral Idiopathic Progressive Sensorineural Hearing Loss" for any association/correlation with nature of disease.

Spectrum of Handicap in Unilateral Sensorineural Hearing Loss.

Unilateral Sensorineural Hearing Loss (USNHL) can present with varying symptoms apart from hearing loss, such as dizziness and tinnitus. Impaired sound localization, inability to identify speech in noise and decreased temporal summation can significantly impair the daily activities of an individual. This along with dizziness and tinnitus affects the physical, mental and social health as well. The purpose of this study is to assess and correlate the spectrum of handicap faced by USNHL patients. Validated questionnaires were used to evaluate handicap in 42 USNHL patients due to hearing loss (Hearing Handicap Inventory for Adults-HHIA), dizziness (Dizziness Handicap Inventory-DHI) and tinnitus (Tinnitus Handicap Inventory-THI). These handicaps were then correlated with each other using Spearman's correlation coefficient. Statistically significant strong positive correlation of HHIA was seen with DHI (rho = 0.60, p ≤ 0.001) and THI (rho = 0.74, p ≤ 0.001). Similarly, strong positive correlation was seen between emotional subscales of HHIA and DHI (rho = 0.73, p ≤ 0.001). USNHL can lead to significant emotional and social handicap which is compounded in the presence of hearing loss, dizziness and tinnitus. These handicaps are strongly correlated to one another. Hence, a holistic approach is needed for USNHL rehabilitation. There exists a need to develop a comprehensive measure to assess and grade the handicap faced by these patients.

Rare Causes of Unilateral Sensorineural Hearing Loss in Adults: Our Experience.

Bilateral hearing loss is attributed to almost 50% of times with genetic etiology, while most unilateral sensorineural hearing loss (USNHL) are not attributable to it. Limited literature is available on epidemiology of USNHL. Etiology of USNHL is very diverse and vast, it ranges from as common as Meniere's disease to as rare as an electric shock injury. A prospective study was carried out to find rare causes of USNHL in adults. In this manuscript, we present a case series of 7 rare etiologies of USNHL in adults like auditory neuropathy, chemoradiotherapy, dialysis-induced SNHL, common cavity inner ear malformation, multiple sclerosis, acute otitis media-induced SNHL and vertebrobasilar dolichoectasia. This study discusses the rare possible etiologies of USNHL that can be easily missed if these are not ruled out properly. We present these cases to consider these heterogeneous and distinct causes of USNHL because of rarity of these etiologies. If such an etiology is diagnosed in time, they may be managed effectively.