Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite.

Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasite Plasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte- a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which plays an important role in parasite invasion.

Advances in bioinspired nanomaterials managing microbial biofilms and virulence: A critical analysis.

Microbial virulence and biofilm formation stand as a big concern against the goal of achieving a green and sustainable future. Microbial pathogenesis is the process by which the microbes (bacterial, fungal, and viral) cause illness in their respective host organism. 'Nanotechnology' is a state-of-art discipline to address this problem. The use of conventional techniques against microbial proliferation has been challenging against the environment. To tackle this problem, there has been a revolution in this multi-disciplinary field, to address the aspect of bioinspired nanomaterials in the antibiofilm and antimicrobial sector. Bioinspired nanomaterials prove to be a potential antibiofilm and antimicrobial agent as they are non-hazardous to the environment and mostly synthesized using a single-step reduction protocol. They exhibit synergistic effects against bacterial, fungal, and viral pathogens and thereby, control the virulence. In this literature review, we have elucidated the potential of bioinspired nanoparticles as well as nanomaterials as a promising anti-microbial treatment pedagogy and throw light on the advancements in how smart photo-switchable platforms have been designed to exhibit both bacterial releasing as well as bacterial-killing properties. Certain limitations and possible outcomes of these bio-based nanomaterials have been discussed in the hope of achieving a green and sustainable ecosystem.

Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Restored with Cast Post Cores Using 5 Common Luting (Cement) Agents.

BACKGROUND A luting agent is a dental cement used to secure a dental restoration. This study aimed to evaluate retentive strength of 50 endodontically-treated single-rooted mandibular second premolars (extracted) restored using 5 common luting (cement) agents. MATERIAL AND METHODS Fifty single-rooted mandibular second premolars with adequate root length and uniform size/shape were decoronated. After completing endodontic biomechanical preparation and obturation, root canals of all specimens were prepared to receive a cast post core. Depending upon cementation type, CPC specimens were divided in 5 groups (10 each) (Gp): Zinc phosphate (Gp ZP), polycarboxylate (Gp PC), glass ionomer (Gp GI), resin-modified glass ionomer (Gp RGI), and resin cement (Gp RC). Retentive strength was determined using the adhesive failure pull-out test. Mean/standard deviations were calculated for tensile forces (in kilograms) and differences were determined using analysis of variance (ANOVA). Multiple comparison was performed using the t test. A P value of ≤0.05 indicated a statistically significant difference. RESULTS The order of mean tensile strength from higher to lower was Gp RC (21.46) >Gp RGI (18.17) >Gp GI (16.07) >Gp ZP (15.33) >Gp PC (13.63). Differences in retentive strengths between the cements were significant (P≤0.05). Multiple-group comparisons showed that except for Gp ZP and Gp GI, all groups differed significantly from each other. CONCLUSIONS All investigated cements provided optimal retentive strengths, with wide differences between them. Resin cements should be used when CPC removal is not anticipated, while polycarboxylate or zinc phosphate should be used if CPC removal is anticipated.

Dual Leucine Zipper Kinase Regulates Dscam Expression through a Noncanonical Function of the Cytoplasmic Poly(A)-Binding Protein.

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The Drosophila DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3' untranslated region (3'UTR) of Dscam mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic analysis shows that Wnd requires pAbp for promoting presynaptic arbor growth and for enhancing Dscam expression. Our analysis revealed that Dscam mRNAs harbor short poly(A) tails. We identified a region in Dscam 3'UTR that specifically interacts with pAbp. Removing this region significantly reduced Wnd-induced increase in Dscam expression. These suggest that a noncanonical interaction of PABP with the 3'UTR of target transcripts is essential for DLK functions.SIGNIFICANCE STATEMENT The kinase DLK plays key roles in a multitude of neuronal responses, including axon development, neurodegeneration, and nerve injury. Previous studies show that DLK acts via mRNAs to regulate protein synthesis, but how DLK does so is poorly understood. This study demonstrates that DLK regulates the synthesis of Dscam through the poly(A)-binding protein PABP-C. Whereas PABP-C is known as a general translational activator, our study shows that DLK-mediated Dscam expression involves a noncanonical interaction between PABP-C and the Dscam mRNA, which leads to a selective regulation of Dscam translation by PABP-C. Thus, our study provides novel insights into the mechanisms that underlie the function of DLK and regulation of gene expression of PABP-C.

Development and evaluation of Hedyotis corymbosa (L.) extract containing phytosomes: a preclinical approach for treatment of neuropathic pain in rodent model.

PURPOSE: The study was aimed to encapsulate Hedyotis corymbosa extract (HCE) into phytosomes to improve its therapeutic efficacy in neuropathic pain by enhancing the bioavailability of chief chemical constituent Hedycoryside -A (HCA). METHODS: For preparing phytosomes complexes (F1, F2, and F3), HCE and phospholipids were reacted in disparate ratio. F2 was chosen to assess its therapeutic efficacy in neuropathic pain induced by partial sciatic nerve ligation. Nociceptive threshold and oral bioavailability were also estimated for F2. RESULTS: Particle size, zeta potential and entrapment efficiency for F2 were analysed as 298.1 ± 1.1 nm, -3.92 ± 0.41 mV and 72.12 ± 0.72% respectively. F2 gave enhanced relative bioavailability (158.92%) of HCA along with a greater neuroprotective potential showing a significant antioxidant effect and augmentation (p < 0.05) in nociceptive threshold with the diminution in damage to nerves. CONCLUSION: F2 is an optimistic formulation for enhancing the HCE delivery for the effective treatment of neuropathic pain.

Artificial neural network (ANN) and response surface methodology (RSM) algorithm-based improvement, kinetics and isotherm studies of electrocoagulation of oily wastewater.

The work reported here focuses on the oil and grease removal from wastewater by the electrocoagulation process and using modeling and optimization for obtaining the results considering four major operating parameters, viz. current density, pH, electrode distance and reaction time. 31 experiments were designed by design of experiments (DOE) of response surface methodology (RSM) and the analysis of variance (ANOVA) studies confirmed the agreement of the experimental results. Artificial neural network (ANN) was also utilized to determine predicted response using neural networks for 4-10-1 arrangement. Both the responses predicted by RSM and ANN were in alignment with the experimental results. Maximum removal of 78% was attained under the working parameters of 80 A m-2, 3.6 pH, electrode distance of 0.005 m and reaction time of 20 min.

One-Pot Crystallization of 2D and 3D Cobalt-Based Metal-Organic Frameworks and Their High-Performance Electrocatalytic Oxygen Evolution.

Developing highly competent and low-cost earth-plentiful metal-based oxygen evolution reaction (OER) electrocatalysts is critical for future electrochemical conversion technologies and renewable energy systems. Herein, two cobalt-based metal-organic frameworks (Co-MOFs), [Co6(btc)2(DMF)6(HCOO)6] (2D, MOF 1) and [Co3(CHOO)9{DMA}3] (3D, MOF 2), where btc = 1,3,5-benzenetricarboxylic acid, DMF = N,N-dimethylformamide, and DMA = dimethylamine, have been crystallized under hydrothermal conditions, from a single reaction. MOF 1 shows an extraordinary OER performance with 175 mV overpotential to attain 10 mA cm-2 current density with a low Tafel slope value of 80 mV dec-1, whereas MOF 2 achieves 10 mA cm-2 current density at 389 mV overpotential. Two different architecture-based MOFs have been synthesized from a single solution for the very first time. Also, the OER activity of MOF 1 overpowers the commercially used RuO2 and surpasses most of the reported OER electrocatalysts. Post OER characterization of MOF 1 revealed the in situ formation of Co(OH)2 and CoOOH, acting as active sites for the OER process.

An In Vitro Comparative Evaluation of Antimicrobial Efficacy of Propolis, Morinda Citrifolia Juice, Sodium Hypochlorite and Chlorhexidine on Enterococcus faecalis and Candida albicans.

AIM: To evaluate the antimicrobial effectiveness of Propolis, Morinda citrifolia juice, Sodium hypochlorite and Chlorhexidine onEnterococcus feacalis (E. feacalis) and Candida albicans (C. albicans), as endodontic irrigants. MATERIALS AND METHODS: Four clinical isolates and one standard ATCC sample (29212) of E. feacalis and ATCC sample (90028) of C. albicans were inoculated into 5ml of peptone water each and incubated at 37° C for 3 to 4 hours to attain the turbidity corresponding to 0.5 McFarland standard CFU. We followed Disc and well diffusion Kirby-Bauer method to attain the zones of inhibition. RESULTS: Overall comparison of reagents revealed a significant difference among zones of inhibition. The standard concentration of 5% sodium hypochlorite, 2% chlorhexidine, 10% Propolis and 100% Morinda citrifolia juice illustrated the maximum inhibition zone for both test organisms. CONCLUSION: All four reagents had an antimicrobial effect on the microorganisms tested. Sodium hypochlorite and Chlorhexidine were more effectual than Propolis and Morinda citrifolia juice and there was increased antimicrobial efficacy with increasing concentrations. CLINICAL SIGNIFICANCE: A study for finding safe herbal agents that can be used as endodontic irrigants revealed that Propolis, Morinda citrifolia juice has antibiotic properties and can replace routinely used agents thereby limiting the side effects.

Comparison of Fracture Resistance of Heat Cure Resins Polymerized by Conventional and Microwave Methods after Immersion in Artificial Saliva.

AIM: To assess and compare the impact and flexural strength of heat cure acrylic resin polymerized by microwave and conventional methods after immersion in artificial saliva for 2 days, 60 days, 90 days and 120 days. MATERIALS AND METHODS: The present study was carried out on 160 specimens. They were categorized into two groups. Each group consisted of 80 specimens, polymerized either by conventional or microwave methods. All the specimens were immersed in artificial saliva, for varying periods of 2 days, 60 days, 90 days and 120 days. Flexural strength was measured by a universal testing machine and impact strength by Izod impact test. Analysis of the results was done by Statistical Package for the Social Services version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, SPSS version 20.0. Armonk, NY: USA, IBM Corp) for Windows software. RESULTS: Conventionally cured resin had the highest flexural and impact strength values after 2 days of immersion in artificial saliva. There was a significant decrease in strength as the number of days of immersion increased (p < 0.001). CONCLUSION: Conventional acrylic resin polymerized in a water bath exhibited better flexural, and impact strength values than microwave cured the resin. All the samples cured by both methods showed a significant reduction in strength when immersed for a period of 60-90 days and thereafter became static over 120 days. CLINICAL SIGNIFICANCE: As dentures are exposed to moist environment constantly and with time, their strength gets reduced. Prosthodontists should have adequate knowledge regarding the physical properties of materials used for denture preparation and also the pros and cons of different polymerization methods. In our study, conventional acrylic resin polymerized in a micro-wave method exhibited lesser strength values, but they were clinically acceptable; so, this method can be used for curing dentures.

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

BACKGROUND: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. METHODS: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. CONCLUSION: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

Effects of open dumping of MSW on metal contamination of soil, plants, and earthworms in Ranchi, Jharkhand, India.

Influence of open dumping of municipal solid wastes (MSW) on metal contamination of soil, plants, and earthworms in Ranchi, Jharkhand, India, was studied over 6-month period. Dumpsite in the study area exists in two sections, old section where waste dumping has stopped and new section where wastes are currently disposed. Soil around dumpsite had high concentration of Co, Cr, Cu, Pb, and Zn than that at control site. Geoaccumulation index indicated uncontaminated to moderate level of soil contamination at old dumpsite and soil at new dumpsite was found to be uncontaminated. Parthenium hysterophorus, Lantana camara, and Calotropis procera were the main plants found in patchy distribution around dumpsite. Plants exhibited almost similar levels of metal concentration in roots and shoots. P. hysterophorus and L. camara showed high bioaccumulation capacity and low translocation capacity. C. procera showed moderate bioaccumulation capacity and high translocation capacity as the concentration of metals was higher in the shoot. P. hysterophorus and L. camara due to higher bioaccumulation capacity and lower translocation capacity appear to be suitable for phytostabilization of metal-contaminated soil. Earthworms present at the dumpsite showed high concentration of Cr, Cu, Pb, and Zn with bioconcentration factor > 1. Results highlights that soil contamination due to metals is occurring at the dumpsite which is also leading to transfer of metals to plants and earthworms which can pose serious risk to environment and human health. The plants identified can be used for decontamination of metals from the dumpsite.

Visual and Real-Time Event-Specific Loop-Mediated Isothermal Amplification Based Detection Assays for Bt Cotton Events MON531 and MON15985.

Bt cotton events MON531 and MON15985 are authorized for commercial cultivation in more than 18 countries. In India, four Bt cotton events have been commercialized; more than 95% of total area under genetically modified (GM) cotton cultivation comprises events MON531 and MON15985. The present study reports on the development of efficient event-specific visual and real-time loop-mediated isothermal amplification (LAMP) assays for detection and identification of cotton events MON531 and MON15985. Efficiency of LAMP assays was compared with conventional and real-time PCR assays. Real-time LAMP assay was found time-efficient and most sensitive, detecting up to two target copies within 35 min. The developed real-time LAMP assays, when combined with efficient DNA extraction kit/protocol, may facilitate onsite GM detection to check authenticity of Bt cotton seeds.

Performance evaluation of vinasse treatment plant integrated with physico-chemical methods.

With an objective to assess environmental management criteria of a vinasse treatment plant (VTP) and to evaluate the critical environmental parameters, a study was undertaken in a multi-product (packaged apple juice, distillery, brewery, packaged drinking water) brewery-cum-distillery unit. The facility with a volumetric loading rate of 11-15 kg COD m(-3).day, 3.6-4.5 h hydraulic retention time and 20 g l(-1) VSS had a scientifically managed technically sound effluent treatment system. While the water quality parameters were found within the acceptable limits, there was 99.07% reduction in BOD, from 43140.0 to 398.0 mg l(-1) and 98.61% reduction in COD from 98003.0 to 1357.0 mg l(-1). There was appreciable improvement in mixed liquor suspended solids (MLSS), mixed liquorvolatile suspended solids (MLVSS) and sludge volume index (SVI). A striking feature was the integrated aerobic-anaerobic highly efficient Up-flow Anaerobic Sludge Blanket (UASB) treatment for biodegradation and energy production that reduced energy and space needs, producing utilisable end-products and net savings on the operational cost. The end-point waste management included terminal products such as fertile sludge, cattle feed supplement, recyclable water and biogas. Vast lagoons with combined aerobic-anaerobic approaches, biogasification unit, sludge recovery, remediated irrigable water were the notable attributes.

Measurement of Poly A Tail Length from Drosophila Larva Brain and Cell Line.

Polyadenylation is a crucial posttranscriptional modification that adds poly(A) tails to the 3' end of mRNA molecules. The length of the poly(A) tail is tightly regulated by cellular processes. Dysregulation of mRNA polyadenylation has been associated with abnormal gene expression and various diseases, including cancer, neurological disorders, and developmental abnormalities. Therefore, comprehending the dynamics of polyadenylation is vital for unraveling the complexities of mRNA processing and posttranscriptional gene regulation. This paper presents a method for measuring poly(A) tail lengths in RNA samples isolated from Drosophila larval brains and Drosophila Schneider S2 cells. We employed the guanosine/inosine (G/I) tailing approach, which involves the enzymatic addition of G/I residues at the 3' end of mRNA using yeast poly(A) polymerase. This modification protects the RNA's 3' end from enzymatic degradation. The protected full-length poly(A) tails are then reverse-transcribed using a universal antisense primer. Subsequently, PCR amplification is performed using a gene-specific oligo that targets the gene of interest, along with a universal sequence oligo used for reverse transcription. This generates PCR products encompassing the poly(A) tails of the gene of interest. Since polyadenylation is not a uniform modification and results in tails of varying lengths, the PCR products display a range of sizes, leading to a smear pattern on agarose gel. Finally, the PCR products are subjected to high-resolution capillary gel electrophoresis, followed by quantification using the sizes of the poly(A) PCR products and the gene-specific PCR product. This technique offers a straightforward and reliable tool for analyzing poly(A) tail lengths, enabling us to gain deeper insights into the intricate mechanisms governing mRNA regulation.

Rab11 suppresses neuronal stress signaling by localizing Dual leucine zipper kinase to axon terminals for protein turnover.

Dual Leucine Zipper Kinase (DLK) mediates multiple neuronal stress responses, and its expression levels are constantly suppressed to prevent excessive stress signaling. We found that Wallenda (Wnd), the Drosophila ortholog of DLK, is highly enriched in the axon terminals of Drosophila sensory neurons in vivo and that this subcellular localization is necessary for Highwire-mediated Wnd protein turnover under normal conditions. Our structure-function analysis found that Wnd palmitoylation is essential for its axon terminal localization. Palmitoylation-defective Wnd accumulated in neuronal cell bodies, exhibited dramatically increased protein expression levels, and triggered excessive neuronal stress responses. Defective intracellular transport is implicated in neurodegenerative conditions. Comprehensive dominant-negative Rab protein screening identified Rab11 as an essential factor for Wnd localization in axon terminals. Consequently, Rab11 loss-of-function increased the protein levels of Wnd and induced neuronal stress responses. Inhibiting Wnd activity significantly ameliorated neuronal loss and c-Jun N-terminal kinase signaling triggered by Rab11 loss-of-function. Taken together, these suggest that DLK proteins are constantly transported to axon terminals by Rab11 for protein turnover. Our study demonstrates how subcellular protein localization is coupled to protein turnover for neuronal stress signaling. Highlights: Wnd is highly enriched in axon terminals.Wnd protein turnover by Hiw is restricted in the axon terminals.Protein palmitoylation of Wnd and Rab11 activity is essential for Wnd axonal localization. Rab11 mutations and defective Wnd palmitoylation impair Wnd protein turnover leading to increased Wnd protein levels and neuronal loss. Inhibiting Wnd activity mitigates neuronal stress response caused by Rab11 loss-of-function.

Tracking genetically modified (GM) rice ingredients in samples of packed rice and food products from the marketplace in India: a pilot study for regulatory compliance.

Purpose: More than 20 genetically modified (GM) food crops including rice have been approved in many countries. GM rice and derived products have not yet been approved in India so they are considered as unauthorized genetically modified organisms (GMOs) in the country. Therefore it is important to track whether the rice containing food items, available in the marketplace are GMO-free. Methods: A pilot study was conducted to check the GM status of 30 samples of packed rice grains and processed food products with rice as an ingredient, using polymerase chain reaction (PCR) assays targeting Cauliflower Mosaic Virus 35 S promoter (P-35 S), nopaline synthase terminator (T-nos), phosphinothricin-N-acetyltransferase (pat) and cry1Ac gene, which could cover screening for all the globally approved GM rice events. Results: Based on the results, none of the samples tested were found positive for P-35 S, T-nos, pat and cry1Ac. Conclusion: The unauthorized presence of GM rice ingredients was not detected in the samples tested. Such studies may further be conducted for the testing of GM ingredients derived from cereals other than rice in the food products imported from the country where GM events of respective cereal crop are approved, as a part of regulatory requirement.

Noma in an 18 months Toddler: A Rare Case Report with Review of Literature.

Introduction: Noma is a polymicrobial necrotizing infection of the mouth and face which destroys the soft and hard tissues of the oral and paraoral structures. Malnutrition, poverty, lack of basic hygiene, and chronic disease state etc., possess a risk of developing noma. Noma neonatorum is a progressive gangrenous disease affecting the premature infants. Aim: We present a rare case of noma in an 18 months toddler with a chronic debilitating condition predisposing to the disease progression. Results: The necrotizing infection of the face developed after six months of multiple episodes of chronic blood-tinged diarrhea. The facial defect was managed with release of fibrosis and reconstruction with a superiorly based nasolabial flap. Discussion: Noma reflects extreme malnutrition and poverty with a vast range of etiopathological agents. This case emphasizes the need to understand the host risk factors and etiopathologic agent predisposing to this rare opportunistic and dormant but devastating disease, the morbidities associated with it and measures to prevent it.

Ultrathin MOF nanosheets and their mixed-matrix membranes for ammonia and aliphatic amine sensing in water.

Ultrathin 2D metal-organic frameworks (MOFs) exhibit a myriad of unparalleled properties, rendering them extensively applicable across various fields. Despite this, developing a 2D MOF sensor for detecting hazardous amines in water remains a formidable challenge. To address this issue, we synthesized Ni-btc MOF ultrathin nanosheets with a thickness of approximately 4.15 nm for the detection of amines in water. These nanosheets demonstrated a notable "turn-on" fluorescence response in the presence of ammonia and aliphatic amines. The detection limit for aliphatic amines ranged from 297 to 424 nM, while for ammonia, it reached an impressive low limit of around 42 nM, which is an excellent value compared to other reported MOFs for ammonia sensing in water. Density functional theory calculations elucidated the mechanism underlying fluorescence enhancement. Additionally, a mixed matrix membrane based on MOF nanosheets was fabricated for real-time sensing that exhibits an immediate color change in the presence of ammonia and aliphatic amines.

Gamma-Tubulin 1 (TUBG1) Mutation-Associated Lissencephaly and Microcephaly in an Indian Child: A Rare Case.

Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as "tubulinopathies." The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay, microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a "variant of unknown significance." Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.

"Survival patterns and prognostic factors of gingivobuccal complex squamous cell cancer: A monocentric retrospective chart audit".

OBJECTIVE: To analyze the impact of clinico-pathological prognostic factors on survival in patients with GBC OSCC. To evaluate the association between various clino-pathological and treatment factors influencing the 3-year and 5-year Overall survival (OS), and Disease specific survival (DSS) in patients with lower GBC OSCC. PATIENTS & METHODS: An Institutional Ethical Committee (IEC) approved retrospective chart audit was performed. Biopsy proven squamous cell cancer of gingivobuccal complex (GBC OSCC) patients from 2010 to 2019 who were treated primarily with surgery with or without adjuvant therapy having complete clinicopathological and follow up data were included. Survival outcomes including 2-year, 3-year & 5-year OS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify significant predictor for the survival outcomes. A p-value < 0.05 was considered significant. RESULTS: 183 patients with primary OSCC were identified out of which 83 patients comprised of OSCC of lower GBC. Age (p < 0.001), tumor grade (p = 0.009), pN status (p = 0.002), PNI (p < 0.001), lymph node metastasis (p = 0.002), treatment given (p = 0.02) and adjuvant therapy (p = 0.02) were found as a significant prognostic factor in univariate analysis. CONCLUSION: The OS & DSS of the patients with lower GBC SCC is 78.3%. The 2-year, 3-year, and 5-year OS of the study population was reported to be 95.2%, 87.9%, and 78.8% respectively. PNI & lymph node metastasis were significant prognostic factor for OS with an adjusted hazard ratio 4.91 and 7.75 respectively.