PAEDIATRIC SYMPTOMATIC SEIZURES IN INDIA: UNRAVELLING VARIED ETIOLOGIES AND NEUROIMAGING PATTERNS - A MULTICENTRIC STUDY.

Pediatric neuroimaging presents a unique set of challenges, primarily stemming from the intricacies of normal myelination processes occurring within the initial two years of life. This complexity is particularly pronounced in the context of pediatric epilepsy, where a substantial proportion of neuroimaging cases appears normal, especially in instances of idiopathic or provoked seizures. Nevertheless, abnormalities in neuroimaging tend to manifest in cases of acute or remote symptomatic seizures. Notably, the etiological landscape of seizures in children diverges significantly from that observed in adults, with neurodevelopmental, neurometabolic, and neuro-infectious factors emerging as predominant contributors. This multicentric study, conducted between November 2021 and November 2023, spanned diverse hospitals across various states in India. Encompassing children from birth to 12 years of age experiencing acute and remote symptomatic seizures, the study meticulously documented clinical and demographic profiles. Exclusion criteria were applied, excluding typical febrile seizures and idiopathic epilepsy syndromes to ensure a focused analysis. The study encompassed a total of 109 cases, revealing a spectrum of neuroimaging findings. Noteworthy among these were cortical malformations, including focal cortical dysplasia (12 cases), tuberous sclerosis (6 cases), polymicrogyria (3 cases), hemimegalencephaly (1 case), lissencephaly (1 case), schizencephaly (2 cases), heterotopias (3 cases), cavernous hemangioma (1 case), and AV malformation (1 case). Additionally, neoplastic lesions (6 cases), neurocysticercosis (5 cases), tuberculoma (4 cases), hippocampal sclerosis (3 cases), post-hypoxic and cerebrovascular accident gliosis (3 cases), leukodystrophies (2 cases), and non-lesional cases (58 cases) were documented. Pediatric neuroimaging in symptomatic seizures may present with normal findings, influenced by interpreter bias and the non-uniform availability of 3T MRI across different medical centers. The diverse causative factors for symptomatic seizures underscore the impact of demographic features, including the endemicity of specific infections and birth injuries, on the observed variability across medical centers. These findings underscore the imperative for a comprehensive understanding and standardization in pediatric neuroimaging practices.

Lymph node yield in treatment naïve cases of head and neck squamous cell carcinoma: en bloc lymphadenectomy versus level-by-level dissection.

BACKGROUND: Lymph node yield is an important prognostic factor in head and neck squamous cell carcinoma. Variability in neck dissection sampling techniques has not been studied as a determinant of lymph node yield. METHODS: This retrospective study used lymph node yield and average nodes per level to compare level-by-level and en bloc neck dissection sampling methods, in primary head and neck squamous cell carcinoma cases operated between March 2017 and February 2020. RESULTS: From 123 patients, 182 neck dissections were analysed, of which 133 were selective and the rest were comprehensive: 55 had level-by-level sampling and 127 had undergone en bloc dissection. The level-by-level method yielded more nodes in all neck dissections combined (20 vs 17; p = 0.097), but the difference was significant only for the subcohort of selective neck dissection (18.5 vs 15; p = 0.011). However, the gain in average nodes per level achieved by level-by-level sampling was significant in both groups (4.2 vs 3.33 and 4.4 vs 3, respectively; both p < 0.001). CONCLUSION: Sampling of cervical lymph nodes level-by-level yields more nodes than the en bloc technique. Further studies could verify whether neck dissection sampling technique has any impact on survival rates.

Evaluation of drug candidature: In silico ADMET, binding interactions with CDK7 and normal cell line studies of potentially anti-breast cancer enamidines.

We have recently explored novel class of potentially anti-breast cancer active enamidines in which four molecules 4a-c and 4h showed higher anticancer activity compared to standard drug doxorubicin. As a part of extension of this work, we have further evaluated in silico cheminformatic studies on bioactivity prediction of synthesized series of enamidines using mole information. The normal cell line study of four lead compounds 4a-c and 4h against African green monkey kidney vero strain further revealed that the compounds complemented good selectivity in inhibition of cancer cells. The in silico bioactivity and molecular docking studies also revealed that the compounds have significant interactions with the drug targets. The results reveal that enamidine moieties are vital for anti-breast cancer activity as they possess excellent drug-like characteristics, being potentially good inhibitors of cyclin dependent kinases7 (CDK7).

Cytotoxic, DNA Cleavage and Pharmacokinetic Parameter Study of Substituted Novel Furan C-2 Quinoline Coupled 1, 2, 4-Triazole and Its Analogs.

BACKGROUND: Furan, quinoline and triazoles are known for their wide spectrum biologically active molecules. A series of novel furan C-2 quinoline and 1, 2, 4-triazole (FQT) coupled hybrids were designed and synthesized to evaluate for their DNA cleavage and cytotoxic studies. OBJECTIVES: In this work we describe the synthesis and biological evaluation of furan C-2 quinoline coupled triazoles exposed for cytotoxic and DNA cleavage study. METHODS: The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gelelectrophoresis and the cytotoxic activity were carried out by MTT assay method. RESULTS: The results revealed that, the molecules 7(a-o) did cleave the DNA completely with no trace of fragments at 100 µg concentration, on the other hand, cytotoxic assay was achieved by two different human cancer cell lines (melanoma cell line-A375 and breast cancer cell line MDA-MB 231). Among the synthesized compounds 7a, 7b, 7c and 7k exhibited potent cytotoxic activity with IC50 values ranging from 2.9, 4.0, 7.8 and 5.1 µg/ml against A375 and 6.2, 9.5, 11.3 and 7.3 µg/ml against, MDA-MB 231, respectively. CONCLUSION: In synthesized compounds 7(a-o) exhibited complete DNA cleavage at 100 µg/ml and the compounds 7a, 7b, 7c and 7k showed very less cytotoxic in nature. The structure activity relationship revealed that, the presence of halogen group/atoms at para position of phenyl ring remarkably enhanced the DNA cleavage and cytotoxic activities among the synthesized compounds.

AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress.

The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4-/- MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53-/-, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil.

Potency dependent activity of homeopathic nanomedicine- classical and quantum electrodynamical approach

The effect of homeopathic medicine on biological and physical system is directly related to its potency [1]. However, from physico-chemical point of view it is difficult to explain this effect at such high dilution, as then the existence of even trace amount of particle is questionable. It has been reported that during the process of potentization, a large amount of mechanical energy gets transferred to the medium due to succussion [2]. This energy in all probability reduces the size of the drug aggregates. The drug then penetrates easily through the membrane barrier, and thereby gives rise to enhanced activity of the medicine. It has been experimentally proved by us and supported by others that indeed a reduction of size of the aggregates takes place with increase in potency [3]. Using five different homeopathic medicines, their sizes at three different potencies have been estimated and a general mathematical expression relating the size of the particle (Y) and the corresponding potency (X) has been derived as follows Y = a X -n. (AU)

A Short Term Subjective and Objective Analysis of Modified Endoscopic Lothrop's Procedure and Its Functional Outcome: Our Experience.

To study the short-term functional outcomes of the endoscopic modified Lothrop procedure with well defined subjective and objective criteria. It's a retrospective cohort study with chart review carried out at a tertiary referral center. 31 patients with chronic frontal sinusitis who underwent endoscopic modified Lothrop's procedure with uncinate preservation during the period Jan 2011-2014 were followed up for a period of minimum 6 months. Assessment was done post-operatively based on subjective severity score and Kennedy's 5 point endoscopic criteria. Subjective improvement was seen in all symptoms whereas statistically significant improvement was found for the three parameters headache (p < 0.025), nose block (p < 0.03) and rhinorrhea (p < 0.05). Post operative nasal endoscopy revealed crusting and polypoidal mucosa in few patients which were managed conservatively. Asymptomatic narrowing of ostium seen in two patients. No complications were identified. The study illustrates the benefit obtained from endoscopic modified Lothrop's surgery in chronic frontal sinusitis refractory to medical treatment and standard endoscopic sinus surgery.

Reprogramming of Molecular Switching Events in UPR Driven ER Stress: Scope for Development of Anticancer Therapeutics.

The incitement of unfolded protein response (UPR) during endoplasmic reticulum (ER) stress by diverse intracellular (hypoxia, nutrient deprivation, etc.) or extracellular (environmental or drug induced) stimuli is considered a major threat for perturbing cellular homeostasis leading to the aggregation of unfolded proteins inside the cell. The catastrophic UPR events emerge as a prime cellular adaptation by remodeling cancer cell signaling and restoring ER homeostasis in favor of tumor growth. The transient ER stress protects cancer cells from undergoing apoptosis, whereas the prolonged stress response further activates many cell death pathways. The present review summarizes the UPR mediated triggering of transcriptional and translational reprogramming, which will provide novel therapeutic strategies towards pro-death mechanisms rather than a cellular adaptation in tumorigenesis. Nonetheless, the current topic also points out the reprogramming of emerging molecular switching events by complex UPR-mediated signaling to trigger apoptosis. The novel agents from various natural, semi-synthetic and synthetic sources that target ER stress signaling pathway to modulate selectively the UPR phenomena with preclinical efficacy are outlined. Since major emphasis on ER stress-induced transcriptional and translational reprogramming remains to be explored, we believe that the current subject will instigate more attention from the biomedical researchers in this certain research direction.

B Cell-Activating Transcription Factor Plays a Critical Role in the Pathogenesis of Anti-Major Histocompatibility Complex-Induced Obliterative Airway Disease.

Antibodies (Abs) against major histocompatibility complex (MHC) results in T helper-17 (Th17)-mediated immunity against lung self-antigens (SAgs), K-α1 tubulin and collagen V and obliterative airway disease (OAD). Because B cell-activating transcription factor (BATF) controls Th17 and autoimmunity, we proposed that BATF may play a critical role in OAD. Anti-H2K(b) was administered intrabronchially into Batf (-/-) and C57BL/6 mice. Histopathology of the lungs on days 30 and 45 after Ab administration to Batf (-/-) mice resulted in decreased cellular infiltration, epithelial metaplasia, fibrosis, and obstruction. There was lack of Abs to SAgs, reduction of Sag-specific interleukin (IL)-17 T cells, IL-6, IL-23, IL-17, IL-1ß, fibroblast growth factor-6, and CXCL12 and decreased Janus kinase 2, signal transducer and activator of transcription 3 (STAT3), and retinoid-related orphan receptor γT. Further, micro-RNA (miR)-301a, a regulator of Th17, was reduced in Batf (-/-) mice in contrast to upregulation of miR-301a and downregulation of protein inhibitor of activated STAT3 (PIAS3) in anti-MHC-induced OAD animals. We also demonstrate an increase in miR-301a in the bronchoalveolar lavage cells from lung transplant recipients with Abs to human leukocyte antigen. This was accompanied by reduction in PIAS3 mRNA. Therefore, we conclude that BATF plays a critical role in the immune responses to SAgs and pathogenesis of anti-MHC-induced rejection. Targeting BATF should be considered for preventing chronic rejection after human lung transplantation.

Blood loss in spinal tumour surgery and surgery for metastatic spinal disease: a meta-analysis.

There is currently no consensus about the mean volume of blood lost during spinal tumour surgery and surgery for metastatic spinal disease. We conducted a systematic review of papers published in the English language between 31 January 1992 and 31 January 2012. Only papers that clearly presented blood loss data in spinal surgery for metastatic disease were included. The random effects model was used to obtain the pooled estimate of mean blood loss. We selected 18 papers, including six case series, ten retrospective reviews and two prospective studies. Altogether, there were 760 patients who had undergone spinal tumour surgery and surgery for metastatic spinal disease. The pooled estimate of peri-operative blood loss was 2180 ml (95% confidence interval 1805 to 2554) with catastrophic blood loss as high as 5000 ml, which is rare. Aside from two studies that reported large amounts of mean blood loss (> 5500 ml), the resulting funnel plot suggested an absence of publication bias. This was confirmed by Egger's test, which did not show any small-study effects (p = 0.119). However, there was strong evidence of heterogeneity between studies (I(2) = 90%; p < 0.001). Spinal surgery for metastatic disease is associated with significant blood loss and the possibility of catastrophic blood loss. There is a need to establish standardised methods of calculating and reporting this blood loss. Analysis should include assessment by area of the spine, primary pathology and nature of surgery so that the amount of blood loss can be predicted. Consideration should be given to autotransfusion in these patients.

Modified Stennert's Protocol in Treating Acute Peripheral Facial Nerve Paralysis: Our Experience.

The aim of this study was to know the effect of modified Stennert's protocol on Bell's palsy and delayed onset post traumatic facial nerve paralysis. Retrospective study method which included 26 patients was done. Of this 19 patients had Bell's palsy and seven patients had delayed onset post traumatic facial nerve paralysis. All patients started on modified Stennert's protocol. Nineteen patients were observed and had idiopathic facial nerve paralysis. Fifteen patients showed clinical improvement by the 10th day and by the end of 1 month, 18 patients showed significant symptomatic improvement. One patient had residual defects at 6 months. Of the seven patients with delayed onset post traumatic facial nerve paralysis, three patients had to undergo facial nerve decompression, the remaining four receiving only modified Stennert's protocol. Improvement was seen in three patients by the 10th day. By the end of 1 month a total of five patients showed significant symptomatic improvement. Our experience suggests that regardless of the cause, sudden onset facial paralysis responds favorably to administration of modified Stennert's regimen, resulting in faster recovery and lesser sequelae.

KTP Laser in Laryngeal Amyloidosis: Five Cases with Review of Literature.

To study the clinical presentation and review the options in the management of laryngeal amyloidosis. To study the efficacy of KTP 532 laser in the excision of laryngeal amyloidosis. Study was conducted in our department in a tertiary care hospital between Jan 2001 and Feb 2010. We report five patients who presented with hoarseness of voice and localized laryngeal lesions. The biopsy proven laryngeal amyloidosis lesions were excised microendoscopically using KTP 532 laser in three patients and other two patients were kept only on follow-up as they refused further surgery. The patients were evaluated for systemic amyloidosis. The average duration of follow up was 2.6 years (3 months 6 years). All the five patients in our study were asymptomatic with no evidence of recurrence at their last follow up. In our small case series, KTP 532 laser excision of the laryngeal amyloidosis had a favorable outcome. Long term follow up is required to rule out recurrence and systemic involvement.

Role of Le Fort type I osteotomy approach in juvenile nasopharyngeal angiofibroma.

Le Fort type I osteotomy is a fracture that extends from the pyriform aperture to each of the pterygoid plates, resulting in the detachment of the upper jaw from the cranial base. A retrospective study was conducted on 12 patients with juvenile nasopharyngeal angiofibroma (JNA) who underwent the Le Fort type I approach. Preoperatively, all cases were investigated with computed tomographic scans with contrast and angiography with embolisation. This paper highlights the surgical technique, results and treatment morbidity. The average age of the patients was 21 years, average duration of surgery was 3.2h and average blood loss was 550 ml. All cases had significant symptomatic improvement postoperatively. At 1 year follow up, the authors encountered dental malocclusion in one case and no recurrence of JNA. The Le Fort I osteotomy approach is an excellent approach for the excision of JNA because it allows good surgical exposure, better haemostasis, is cosmetically more acceptable and has a very low morbidity.

Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia.

Microglial activation has been implicated as one of the causative factors for neuroinflammation in various neurodegenerative diseases. The sphingolipid metabolic pathway plays an important role in inflammation, cell proliferation, survival, chemotaxis, and immunity in peripheral macrophages. In this study, we demonstrate that sphingosine kinase1 (SphK1), a key enzyme of the sphingolipid metabolic pathway, and its receptors are expressed in the mouse BV2 microglial cells and SphK1 alters the expression and production of proinflammatory cytokines and nitric oxide in microglia treated with lipopolysaccharide (LPS). LPS treatment increased the SphK1 mRNA and protein expression in microglia as revealed by the RT-PCR, Western blot and immunofluorescence. Suppression of SphK1 by its inhibitor, N, N Dimethylsphingosine (DMS), or siRNA resulted in decreased mRNA expression of TNF-alpha, IL-1beta, and iNOS and release of TNF-alpha and nitric oxide (NO) in LPS-activated microglia. Moreover, addition of sphingosine 1 phosphate (S1P), a breakdown product of sphingolipid metabolism, increased the expression levels of TNF-alpha, IL-1beta and iNOS and production of TNF-alpha and NO in activated microglia. Hence to summarize, suppression of SphK1 in activated microglia inhibits the production of proinflammatory cytokines and NO and the addition of exogenous S1P to activated microglia enhances their inflammatory responses. Since the chronic proinflammatory cytokine production by microglia has been implicated in neuroinflammation, modulation of SphK1 and S1P in microglia could be looked upon as a future potential therapeutic method in the control of neuroinflammation in neurodegenerative diseases.

Endoscopic repair of cerebrospinal fluid rhinorrhea - Manipal experience.

Otolaryngologists play a major role in the management of cerebrospinal fluid (CSF) rhinorrhea. A thorough understanding of the underlying pathophysiology and the various treatment options available is essential to achieve the best possible results.In this paper, we are highlighting the pathophysiology, diagnosis and surgical technique involved in the repair of cerebrospinal fluid rhinorrhea. A retrospective study conducted in the department of ENT and Head and Neck Surgery, Kasturba Hospital, Manipal is presented to highlight our experience with cerebrospinal fluid rhinorrhea.Eleven patients were managed in the department of otolaryngology between 1999 and 2005. Seven had spontaneous CSF rhinorrhea, three were due to trauma and one iatrogenic, following surgery. Commonest anatomic site of leak was the cribriform plate in 4 cases. Other sites included sphenoid [2], lateral lamella [2], fovea ethmoidalis [2] and olfactory groove [1]. Onlay technique was performed in 10 out of 11 patients. Closure was successful in 10 out of 11 cases in the first attempt. One patient underwent revision surgery. Patients were followed up for a period ranging from 3 months to 3 years.CSF rhinorrhea is a potentially fatal condition which requires precise and urgent treatment. The transnasal endoscopic repair of CSF leak has a high success rate with low morbidity when performed by experienced endoscopic sinus surgeons. Our experience in managing this condition is presented.

Role of KTP-532 laser in management of oral submucous fibrosis.

INTRODUCTION: Oral submucous fibrosis is a chronic disease characterised by progressive inability to open the mouth. Various treatment modalities are available for its management, but these have largely been ineffective. MATERIALS AND METHODS: Nine cases of oral submucous fibrosis underwent a release procedure using a KTP-532 laser, from March 2005 to January 2006, within the ENT-head and neck surgery department of a tertiary centre. RESULTS: Pre- and post-operative mouth-opening was compared using the Wilcoxon signed rank test, and a significant difference observed (Z = -2.690, p = 0.007). Follow up over an average period of 12 months showed encouraging results. CONCLUSION: This preliminary study indicated that adequate release of oral submucous fibrosis can be achieved by using a KTP-532 laser release procedure, with minimal morbidity and satisfactory results. These promising results should encourage more widespread use of this technique in the management of this condition.

Hyalinizing clear cell carcinoma of the base of tongue.

Hyalinizing clear cell carcinoma is a rare, low-grade neoplasm of the minor salivary glands. It is composed exclusively of epithelial cells with optically clear cytoplasm. There are only a few isolated cases reported in the literature involving the base of tongue. The treatment of choice is wide excision and selective neck dissection, with or without radiotherapy. The prognosis of these tumours is good. A 57-year-old male patient presented with a lesion in the base of tongue, which was well enhanced on contrast computerized tomography scan. Once confirmed by biopsy, the hyalinizing clear cell carcinoma was resected via a transcervical approach. The patient underwent postoperative radiotherapy. There was no evidence of locoregional recurrence or distant metastasis at 18 months of follow up.

Sphenochoanal polyp with heterotopic glial tissue.

An isolated polyp arising from the sphenoid sinus is rare. Due to the presence of important structures adjacent to the sphenoid sinus, a proper pre-operative radiological and nasal endoscopic evaluation is mandatory, along with a neurological and ophthalmological assessment. We report the case of a 23-year-old man with a sphenochoanal polyp with heterotopic glial tissue in the stroma. A Medline search did not reveal any previously reported cases of glial tissue in the sphenoid sinus presenting as a sphenochoanal polyp.

Metastatic renal cell carcinoma presenting with epistaxis.

Renal cell carcinoma is a slow growing malignancy of the kidney that has a high propensity for metastasis. It is the most common metastasis reported in the paranasal sinuses. A fifty six year old male patient, an operated case of left renal cell carcinoma presented seven years later with epistaxis. Computerized tomography of the paranasal sinuses and of the abdomen showed a metastatic lesion involving the left nasosinus region and a lesion involving the right kidney with lung metastasis, respectively. Due to the poor prognosis palliative radiotherapy was given.

Endoscopic dacryocystorhinostomy vs KTP 532 laser-assisted endoscopic dacryocystorhinostomy.

OBJECTIVES: Advances in endoscopy and lasers have improved surgical management of chronic nasolacrimal duct obstruction. This is a preliminary comparison between standard and laser assisted endoscopic dacryocystorhinostomy (DCR). STUDY DESIGN: Combined retrospective and prospective study. SETTING: Tertiary referral hospital. PATIENTS AND METHODS: Thirty-eight cases of chronic nasolacrimal duct obstruction underwent endoscopic DCR (26 standard and 12, laser-assisted) and were assessed at 3 and at 6 months postoperatively by nasal endoscopy. RESULTS: Three months postoperatively (n=38), total relief of epiphora among the nonlaser group was 80.76 vs 75% in the laser group (P=0.982). At 6 months (n=19), the laser group had recorded 100% symptomatic relief compared to 85.71% in the nonlaser group (P=0.964). The laser group suffered fewer complications (33.33 vs 46.15% for nonlaser group). CONCLUSION: Lasers show promise in long-term management of duct obstruction and are associated with fewer complications. A larger study is required before and generalization is made.