Isolation, Characterization, and Expression Analysis of NAC Transcription Factor from Andrographis paniculata (Burm. f.) Nees and Their Role in Andrographolide Production.

Andrographis paniculata (Burm. f.) Nees is an important medicinal plant known for its bioactive compound andrographolide. NAC transcription factors (NAM, ATAF1/2, and CUC2) play a crucial role in secondary metabolite production, stress responses, and plant development through hormonal signaling. In this study, a putative partial transcript of three NAC family genes (ApNAC83, ApNAC21 22 and ApNAC02) was used to isolate full length genes using RACE. Bioinformatics analyses such as protein structure prediction, cis-acting regulatory elements, and gene ontology analysis were performed. Based on in silico predictions, the diterpenoid profiling of the plant's leaves (five-week-old) and the real-time PCR-based expression analysis of isolated NAC genes under abscisic acid (ABA) treatment were performed. Additionally, the expression analysis of isolated NAC genes under MeJA treatment and transient expression in Nicotiana tabacum was performed. Full-length sequences of three members of the NAC transcription factor family, ApNAC83 (1102 bp), ApNAC21 22 (996 bp), and ApNAC02 (1011 bp), were isolated and subjected to the promoter and gene ontology analysis, which indicated their role in transcriptional regulation, DNA binding, ABA-activated signaling, and stress management. It was observed that ABA treatment leads to a higher accumulation of andrographolide and 14-deoxyandrographolide content, along with the upregulation of ApNAC02 (9.6-fold) and the downregulation of ApNAC83 and ApNAC21 22 in the leaves. With methyl jasmonate treatment, ApNAC21 22 expression decreased, while ApNAC02 increased (1.9-fold), with no significant change being observed in ApNAC83. The transient expression of the isolated NAC genes in a heterologous system (Nicotiana benthamiana) demonstrated their functional transcriptional activity, leading to the upregulation of the NtHMGR gene, which is related to the terpene pathway in tobacco. The expression analysis and heterologous expression of ApNAC21 22 and ApNAC02 indicated their role in andrographolide biosynthesis.

High-Resolution Computed Tomography of the Temporal Bone in Chronic Otitis Media: An Observational Study at a Tertiary Care Center in Jharkhand, India.

INTRODUCTION: Chronic otitis media refers to middle ear inflammation. A radiological exam is a crucial step in this diagnostic process, in addition to a clinical evaluation and an evaluation by an audiologist. For the development of innovative surgical treatment plans for middle ear otitis media with the aim of minimally invasive surgery, accurate information regarding the extent of lesions is required. This is made possible by a temporal bone imaging test. MATERIALS AND METHODS: The study was conducted at the Rajendra Institute of Medical Sciences (RIMS), a tertiary care facility in Ranchi, Jharkhand, India. The research was conducted between June 1, 2021, and October 31, 2022. In this prospective observational study, 50 patients who visited the otorhinolaryngology clinic at RIMS Ranchi were the participants. RESULTS: The median age was 26 years, there was a male-to-female ratio of 1.63 to 1, and the vast majority (84%) were from lower socioeconomic classes. High-resolution computed tomography has been shown to be highly sensitive and specific in identifying conditions including scutum erosion, malleus erosion, pneumatization type, mastoiditis, mastoid abscess, and morphological abnormalities such as low-lying dura. CONCLUSION: The semicircular canal, fallopian canal, dural plate, and sigmoid sinus may all be clearly defined by non-contrast computed tomography of the temporal bone in erosion in cases of otitis media.

Ossifying Fibroma: A Case Report of an Unusual Presentation of Angiodysplastic Disease with Review of Literature.

Ossifying fibroma is a nonneoplastic developmental disease of osseous tissue seen rarely in association with Sturge-Weber syndrome. It is a lesion of unknown aetiology, uncertain pathogenesis, and diverse histopathology. The aim of this study is to report an unusual case of in a 11-year-old male of SWS. The rarity of the case and the fact that ossifying fibroma may be associated with Sturge-Weber syndrome propelled us to report it. Physical examination showed facial asymmetry (due to hemifacial swelling) without any tenderness, fluctuation, ocular pain, or ophthalmoplegia. Imaging studies revealed a solid mass involving the left maxilla and orbital floor. A conservative therapeutic approach to these lesions may be sufficient to relieve signs and symptoms effectively. Periodic follow-up is indicated to detect recurrences or malignant changes in the early stages.

Complications of Acute Bacterial Rhinosinusitis in Contemporary Practice: Lessons Learnt and the Way Ahead.

There are variable presentations of complications of rhinosinusitis, which may be subtle especially due to use of antibiotics. Thus the classical picture as described by Chandler is rarely seen and threshold for diagnosing and treating a complication should be low. To identify possible risk factors for development of complications in acute bacterial rhinosinusitis (ABRS) and suggest a new method of reporting/classifying the complications. We conducted a retrospective study and observed the clinical presentation and risk factors of 9 patients who presented with complications of ABRS in our OPD during a period of 6 years, and then tried to formulate a reporting method based on the risk factors. We identified certain risk factors which include age, gender, sinus involved, extension beyond sinus, history of trauma, anatomical variations, and duration of symptoms. There are possible risk factors for development of complications. These factors can be studied in further details to ascertain their causal relationship in causing these complications. We also suggest a new method of reporting the complications. Such a reporting system would help in accurately identifying the exact severity of the disease, prognosticating the disease and guide treatment.

Comparison of Intraoperative Neural Response Telemetry Results and Postoperative Neural Response Telemetry Results in Case of Children with Congenital Bilateral Severe to Profound Sensorineural Hearing Loss Undergoing Single Sided Cochlear Implantation.

Aim and Objectives: This study is designed to compare the Intra Operative Neural Response Telemetry (NRT) results with Post-Operative NRT results of the cochlear implanted children, to assess the importance of Intra Operative NRT thresholds in device activation and/or switch on of the audio processor and to evaluate the importance of Intra and post operative AutoNRT results in predicting behavioural thresholds during mapping of prelingual Cochlear Implanted children. Materials and methods: A total of thirty (30) children (16 boys, 14 girls) with congenital Bilateral (B/L) severe to profound Sensorineural hearing loss (SNHL) were included in this study. Children between the age range of 12 to 60 months were participated in this study. All the participants were implanted with Nucleus 24 cochlear implant system. In each patient, the intra operative NRT-thresholds were measured for all 22 active electrodes. Then Intra Operative NRT thresholds were correlated with Post-Operative NRT thresholds at the time of switch on and the behavioural map after six months of switch on of the device (Audio Processor). Results: There is a significant enhancement observed in thresholds of postoperative NRT responses which were raised or absent during intraoperative session. There is a gain in NRT thresholds marked after 6 months of postoperative follow up in comparison with first measurement at the time of Switch On of the device but the change not that significant. During postoperative mapping, there was a significant positive correlation noticed between neural response telemetry level measurements and behavioural threshold level. Conclusion: Absent or elevated NRT responses during intraoperative testing for some electrodes especially basal electrodes does not mean that electrode is out of order or outside the cochlea, because an improvement in NRT thresholds usually occurs postoperatively. In case of children with congenital B/L severe to profound SNHL, the NRT values have a very useful role in predicting the behavioural thresholds. Combination of NRT values with behavioural thresholds and observations of Auditory Verbal Therapist can help in providing best suitable Map to the recipient. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03284-x.

Different Approaches to the Overlapping Infratemporal Fossa and Parapharyngeal Spaces: a Case Series and Review of Literature.

Parapharyngeal space and infratemporal fossa are 2 overlapping spaces in head and neck which have complex anatomy with vital neurovascular structures passing through them. Tumors of this region are extremely rare but majority of them (80%) are benign. Benign tumors of this region can lead to swellings in facial region, neck and oropharynx. Dysphagia may be a complaint of the patient. Many of these tumors have malignant potential. Removal of these tumors requires a good understanding of the anatomy of this space so that correct surgical approach can be selected. The surgeon needs to be adept in using the most suitable surgical approach for excision of these tumors. There are various approaches which can be used to access these deeply seated tumors but the issue of prime importance is selecting the appropriate approach for the various tumors here based on their size and their exact location in this complex anatomical space. Inappropriate approach can lead to inadequate tumor excision and can lead to injuries to the neurovascular structures in this region which can cause significant disability. The case series reported here describes the various approaches to this region and highlights the importance of correct selection of the surgical approach.

Laryngeal Trauma Managed with Titanium Mesh Fixation: A Rare Case Report.

Laryngeal fractures are though uncommon they can be potentially life threatening. Comminuted laryngeal cartilage fractures are difficult to manage and various fixation techniques have been described in literature. Outcome results of fixation with different materials can be varied. We report a case of 27 years old male who sustained laryngeal cartilage fracture following accidental fall. Patient underwent emergency tracheostomy and early surgical repair of fractured laryngeal thyroid cartilage with one of the newest techniques "titanium mesh fixation". After a month of surgery tracheostomy tube was removed and patient recovered with good laryngeal function. Titanium mesh fixation gave immediate effective fixation and stability to laryngeal fracture leading to good surgical outcome.

Carotid Body Tumor: A Case Report and Review of Literature.

Carotid body tumour (CBT) is a rare hypervascular tumor in the head and neck region. It develops from neural crest origin paraganglionic tissue which is an arterial chemoreceptor. It presents as a slow growing mass at the carotid bifurcation. Its optimal evaluation and treatment requires involvement of multiple specialities. Because of the high rate of neurovascular complications, resection of this tumor is challenging for surgeons. Early tumor detection, meticulous evaluation and multidisciplinary approach are vital for successful management of these tumors. A case of CBT in a 50 year-old lady managed at our centre is being reported here along with a review of literature.

Dermoid Cyst Floor of Mouth: A Diagnostic Conundrum.

Dermoid cysts are benign tumours of ectodermal origin, commonly seen in young. The clinico-radiological presentation of dermoids can be equivocal, like in our case of a teenager who had painless swelling of floor of mouth. Radiological findings were consistent with cystic lesion but histopathological examination proved it as dermoid cyst.

The Pattern of Disposal Practices of Unused and Expired Medications Among Healthcare Professionals: A Cross-Sectional Survey in Rajendra Institute of Medical Sciences, Ranchi, Jharkhand.

BACKGROUND: Medicines play a crucial role in treating various diseases. Most individuals, in their haste to get through their day, have developed the bad habit of improperly discarding their unwanted or expired prescriptions, which poses a number of risks to human health and contributes to environmental degradation. Disposal procedures of unused and expired pharmaceuticals among health care personnel at tertiary care centers have been the subject of very little research to date. Therefore, the purpose of this study is to examine how medical staff at Rajendra Institute of Medical Sciences in Ranchi, Jharkhand, handle stale or unwanted prescription drugs. METHODS: The design of the study was cross-sectional analytical conducted among 385 health care professionals. Pretested semi-structured questionnaires prepared in Google Forms (Google LLC, Mountain View, California, United States) have been used for evaluation. RESULTS: The completely filled questionnaires were analyzed, evaluated, and expressed in the percentage using Microsoft Excel (Microsoft Corporation, Redmond, Washington, United States). The most common method of disposal of unused and expired medications was throwing them in the dustbin. CONCLUSIONS: In this study, although, all the participants were health care professionals, because of the hectic schedule majority of them used unsafe methods of drug disposal. So, in order to protect our ecosystem, appropriate policy should be made to implement the methods for the safe disposal of unused and expired medications.

Roflumilast improves resolution of sepsis-induced acute kidney injury by retarding late phase renal interstitial immune cells infiltration and leakage in urinary sediments.

Some evidence has demonstrated that both inflammation and immune cell dysregulation are coincident at late phase (post 24 h) of sepsis. The present study was designed to determine the pathological role of hyperinflammation and renal immune cells mobilization during late phase of sepsis induced acute kidney injury (S-AKI) and tests the pharmacological effects of PDE-4 inhibitor on these events. Sepsis was induced by cecal ligation puncture and renal function, oxidative-inflammatory stress biomarkers were assessed after 24 h. PDE-4 inhibitor was administered for 7 days prior to induction of S-AKI. Renal immune cells infiltration during sepsis was analyzed by H&E staining and papanicolaou staining method was used for detecting leukocytes and cast in urinary sediments, periodic acid schiff (PAS) staining was used for detection of brush border loss. AKI developed 24 h post sepsis insult as depicted by increase in serum creatinine, blood urea nitrogen (BUN), renal oxidative stress, and elevated inflammatory biomarkers levels. Moreover, septic rats displayed increased bacterial load, renal expression of phosphodiesterase-4B, 4D isoforms, enhanced vascular permeability, caspase-3 and myeloperoxidase activity, electrolyte imbalance, reduced Na+ K+ ATPase activity, declined cAMP levels, increased interstitial leukocyte infiltration, and leakage in urinary sediments along with histological alterations. Pre-treatment with roflumilast at high dose completely prevented the various AKI associated manifestations in septic rats. Renal hyper-inflammation and leukocyte infiltration was detected in late phase of S-AKI. Roflumilast pre-treatment resolved sepsis induced renal dysfunction and histological damage by suppressing late phase renal immune cells invasion and anti-inflammatory effects mediated by up-regulation of renal cAMP levels.

Assessment of Level of Patient Satisfaction with Day-Care Surgery: An Observational Study.

To assess the level of patient satisfaction with day-care surgery at a tertiary care centre and to find out the different determinants that influence the patient satisfaction. Observational study; Tertiary care hospital in Western India; Patients undergoing Day-care surgery at Dept of ENT from Feb 2018 to Aug 2018; All patients who underwent day-care surgery were given a questionnaire to determine level of satisfaction. On analysis of data according to questions the average score was in the range of 3.5 to 4.22 out of a maximum score of 5. On analysis of data according to domains of patient care the scores ranged from 3.61 to 4.19. Although patients were generally satisfied with the level of care being provided to them there is still scope of improvement.

Effectiveness of bilastine and fexofenadine among allergic Rhinitis patients in Ranchi, Jharkhand, India.

Allergic rhinitis is a worldwide health problem which impairs quality of life and interferes with daily activities. Untreated allergic rhinitis also carries a significant financial burden for the society. Bilastine, a novel second-generation antihistaminic drug that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. Thus, the aim of our study was to compare the effectiveness of bilastine and fexofenadine in treatment of allergic Rhinitis patients. 104 patients were enrolled who have fulfilled the inclusion criteria for the study from the OPD of Ear, Nose and Throat Department. Patients were divided randomly in two groups A and B. Patients of group A were allowed to take tab Bilastine 20 mg OD whereas, patients of group B were allowed to take tab. Fexofenadine Hydrochloride 120 mg OD orally for two weeks. The baseline Total Nasal Symptom Score (TNSS) were compared between two groups. The study findings showed that the mean TNSS was significantly reduced in our study group. Baseline TNSS was 13.55 and 13.45 in Group A and Group B respectively. Reduction in this parameter first become apparent in the 24 hours and maintained till 2nd week. Bilastine showed significant improvement in quality of life of Allergic rhinitis patients and proved to be more effective than fexofenadine in reducing the TNSS score, when used alone in allergic rhinitis patient.

Emerging roles of NAC transcription factor in medicinal plants: progress and prospects.

Transcriptional factors act as mediators in regulating stress response in plants from signal perception to processing the directed gene expression. WRKY, MYB, AP2/ERF, etc. are some of the major families of transcription factors known to mediate stress mechanisms in plants by regulating the production of secondary metabolites. NAC domain-containing proteins are among these large transcription factors families in plants. These proteins play impulsive roles in plant growth, development, and various abiotic as well as biotic stresses. They are involved in regulating the different signaling pathways of plant hormones that direct a plant's immunity against pathogens, thereby affecting their immune responses. However, their role in stress regulation or defence mechanism in plants through the secondary metabolite biosynthesis pathway is studied for very few cases. Emerging concern over the requirement of medicinal plants for the production of biocompatible drugs and antibiotics, the study of these vast, affecting proteins should be focused to improve their qualitative and quantitative production further. In medicinal plants, phytochemicals and secondary metabolites are the major biochemicals that impose antimicrobial and other medicinal properties in these plants. This review compiles the NAC transcription factors reported in selected medicinal plants and their possible roles in different mechanisms. Further, the comprehensive understanding of the molecular mechanism, genetic engineering, and regulation responses of NAC TFs in medicinal plants, can lead to improvement in stress response, immunity, and production of usable secondary metabolites.

Management outcomes of mucormycosis in COVID-19 patients: A preliminary report from a tertiary care hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a significant health problem worldwide. The unprecedented surge of mucormycosis in patients with COVID-19 is a new emerging challenge. Although a few studies documenting high incidence of mucormycosis in COVID -19 patients have recently emerged in literature, data pertaining to treatment outcomes in such cohorts is lacking. Here, we report our experience in management of mucormycosis in COVID-19 patients at our tertiary care centre. METHOD: The clinical, imaging, histopathological and treatment data of 20 patients with mucormycosis (in setting of COVID-19) was analysed. RESULTS: 35% and 65 % of cases developed mucormycosis in setting of active and recovered COVID-19 infections respectively. Diabetes mellitus was documented in 80% cases, with 55% demonstrating HbA1c >10%. Steroid was administered in 80% during COVID-19 illness. Imaging demonstrated paranasal sinus (PNS), orbital and intracranial extension in 100%, 55% and 20% patients respectively. All received amphotericin and underwent endoscopic debridement, 20% underwent orbital decompression and 5% maxillectomy with orbital exenteration. 6/20(30%) patients died (4 with rhino-orbito-cerebral disease, 1 with extensive orbito-maxillary involvement and 1 sino-nasal disease). All 6 patients received steroids and documented poor glycaemic control. CONCLUSION: The strong association of hyperglycemia and steroid intake with mucormycosis in COVID-19 cases warrants judicious use of corticosteroids and optimal glycaemic control. Our study highlights that good clinical outcome can be achieved in invasive mucormycosis provided prompt treatment is instituted with aggressive surgical debridement and antifungal medication.

Wnt/ß-Catenin Antagonist Pyrvinium Exerts Cardioprotective Effects in Polymicrobial Sepsis Model by Attenuating Calcium Dyshomeostasis and Mitochondrial Dysfunction.

Calcium dysregulation and mitochondrial dysfunction are key elements in the development of sepsis-induced cardiac dysfunction. Evidences have suggested that inhibition of Wnt/ß-Catenin signalling prevents cardiac dysfunction and remodelling in surgical, hypertension and pressure overload models. The present study investigated the effects of Wnt/ß-Catenin inhibitor on calcium overload and mitochondrial dysfunction in rat sepsis model of cardiomyopathy. Induction of sepsis by cecal ligation puncture (CLP) resulted in the up-regulation of cardiac ß-catenin transcriptional levels and cardiac dysfunction depicted by increased serum lactate dehydrogenase, CK-MB levels reduced maximum (dp/dt max.) and minimum developed pressure (dp/dt min.), increased LVEsDP and relaxation constant tau values. Moreover, oxidative and inflammatory stress, immune cell infiltration, increased myeloperoxidase activity, enhanced caspase-3 activity and fibronectin protein levels were observed in septic rat's heart. Also, septic rat's heart displayed mitochondrial dysfunction due to mPTP opening, increased calcium up-regulation in left ventricular apex tissues and whole heart, increased collagen staining, necrosis and structural damage. Pre-treatment with Wnt/ß-Catenin antagonist attenuated sepsis-induced serum and tissue biochemical changes, cardiac dysfunction and structural alterations by inhibiting mitochondrial mPTP opening and restricting calcium overloading in cardiac tissue.

Audiological and Surgical Outcomes of Pediatric Cochlear Implantation in Mondini's Dysplasia: Our Experience.

OBJECTIVES: Aim of present study is to compare audiological and surgical outcomes in prelingual deaf children with Mondini's dysplasia (MD) and those with normal inner ear anatomy. MATERIALS AND METHODS: Retrospective data was collected from Jan 2008 to Dec 2016. Children with bony IEM other than MD, syndromic association, multiple disabilities, those lost to follow up, and perilingual or postlingual deafness were excluded from study. Audiological outcomes for auditory perception (CAP score) and speech intelligibility (SIR score) was noted for a follow up period of 1 year. RESULTS: Mean age at implantation was 2.8 years (Range of 2 to 6 years). 2 patients had intraoperative CSF ooze which was controlled intraoperatively by conservative measures. Post operative facial nerve function was normal in all patients. None of the patient in either group had any complications at one year of follow up period. There was statistically significant improvement in CAP - SIR score in Group A at 6 - 12 months compared to pretreatment. There was no statistically significant difference between the 2 groups in terms of CAP - SIR score at 6 - 12 months. CONCLUSION: The study stresses the fact that cochlear implantation can be safely performed in children with MD although there is a risk of intraoperative CSF leak which can be controlled intraoperatively. Cochlear implantation in children with MD has good surgical, auditory and speech outcomes at par with children with normal bony inner ear anatomy.

"Adenosine an old player with new possibilities in kidney diseases": Preclinical evidences and clinical perspectives.

Renal injury might originate from multiple factors like ischemia reperfusion (I/R), drug toxicity, cystic fibrosis, radio contrast agent etc. The four adenosine receptor subtypes have been identified and found to show diverse physiological and pathological roles in kidney diseases. The activation of A1 adenosine receptor (A1) protects against acute kidney injury by improving renal hemodynamic alterations, decreasing tubular necrosis and its inhibition might facilitate removal of toxin or drug metabolite in chronic kidney disease models. Furthermore, recent findings revealed that A2A receptor subtype activation regulates macrophage phenotype in experimental models of nephritis. Interestingly the emerging role of adenosine kinase inhibitors in kidney diseases has been discussed which act by increasing adenosine availability at target sites and thereby promote A2A receptor stimulation. In addition, the least explored adenosine receptor subtype A3 inhibition was observed to exert anti- oxidant, immunosuppressive and anti-fibrotic effects, but more studies are required to confirm its benefits in other renal injury models. The clinical studies targeting A1 receptor in patients with pre-existing kidney disease have yielded disappointing results, perhaps owing to the origin of unexpected neurological complications during the course of trial. Importantly, conducting well designed clinical trials and testing adenosine modulators with lesser brain penetrability could clear the way for clinical approval of these agents for patients with renal functional impairments.

Development of Novel Genomic Simple Sequence Repeat (g-SSR) Markers and Their Validation for Genetic Diversity Analyses in Kalmegh [Andrographis paniculata (Burm. F.) Nees].

Kalmegh (Andrographis paniculata (Burm. F.) Nees) is one of the most important medicinal plants and has been widely explored as traditional medicine. To exploit its natural genetic diversity and initiations of molecular breeding to develop novel cultivars or varieties, developments of genomic resources are essential. Four microsatellite-enriched genomic libraries-(CT)14, (GT)12, (AG)15 and (AAC)8-were constructed using the genomic DNA of A. paniculata. Initially, 183 recombinant colonies were screened for the presence of CT, GT, AG, and AAC microsatellite repeats, out of which 47 clones found positive for the desired simple sequence repeats (SSRs). It was found that few colonies had more than one desirable SSR. Thus, a sum of 67 SSRs were designed and synthesized for their validation among 42 A. paniculata accessions. Out of the 67 SSRs used for genotyping, only 41 were found to be polymorphic. The developed set of g-SSR markers showed substantial genetic variability among the selected A. paniculata accessions, with an average polymorphic information content (PIC) value of 0.32. Neighbor-joining tree analysis, population structure analysis, analysis of molecular variance (AMOVA), and principal coordinate analysis (PCoA) illustrated the considerable genetic diversity among them. The novel g-SSR markers developed in the present study could be important genomic resources for future applications in A. paniculata.

Pan-genome analysis and ancestral state reconstruction of class halobacteria: probability of a new super-order.

Halobacteria, a class of Euryarchaeota are extremely halophilic archaea that can adapt to a wide range of salt concentration generally from 10% NaCl to saturated salt concentration of 32% NaCl. It consists of the orders: Halobacteriales, Haloferaciales and Natriabales. Pan-genome analysis of class Halobacteria was done to explore the core (300) and variable components (Softcore: 998, Cloud:36531, Shell:11784). The core component revealed genes of replication, transcription, translation and repair, whereas the variable component had a major portion of environmental information processing. The pan-gene matrix was mapped onto the core-gene tree to find the ancestral (44.8%) and derived genes (55.1%) of the Last Common Ancestor of Halobacteria. A High percentage of derived genes along with presence of transformation and conjugation genes indicate the occurrence of horizontal gene transfer during the evolution of Halobacteria. A Core and pan-gene tree were also constructed to infer a phylogeny which implicated on the new super-order comprising of Natrialbales and Halobacteriales.