Towards a low-emission resource circulation of valuable metals from municipal solid waste incineration fly ash.

The incineration fly ash (IFA) resulting from municipal solid waste combustion is laden with heavy metals, necessitating proper treatment not only for environmental management but also to reclaim the metal values. The surge in non-traditional metals like cobalt as emerging contaminant within IFA samples further attracts to address this issue. In response, the hydrometallurgical recycling of a cobalt-bearing IFA has been studied. Thereby, approximately 98 % zinc and 96 % cobalt were leached using a 1.0 mol/L H2SO4 solution at 90 °C and 1 h of leaching time. In-depth analysis of the leaching process unveiled metals' dissolution primarily via the ion-exclusion mechanism, as evidenced by lower diffusion coefficients (between 10-9 and 10-11 m2/s) and activation energies (9.6-14.9 kJ/mol). Above 99 % separation of zinc from the cobalt-bearing leach liquor was achieved by extraction with 1.0 mol/L D2EHPA at an equilibrium pH below 3.0, followed by stripping with a 2.0 mol/L H2SO4 solution. Cobalt, remained in the raffinate was efficiently precipitated by adding a 20 % excess dosage of oxalic acid to the stoichiometric ratio of C2O42-:Co2+, resulting in only 5 mg/L cobalt left in the solution when precipitation occurred at a pH of 2.8. Additionally, the conversion of CoC2O4 to high-purity Co3O4 was conducted through heat-treatment at 600 °C. The resulting Co3O4 was mixed with Li2CO3 at a Li/Co molar ratio of 1.1, yielding a LiCoO2 precursor that exhibited good electrochemical properties with a capacity of 128 mAh/g, thus affirming the high quality of the recycled cobalt. A comprehensive life-cycle assessment of the recycling process revealed that cobalt precipitation alone contributes approximately 50 % of the total global warming potential (GWP = 4.2624 kg CO2-eq). Notably, this value is remarkably lower than the GWP reported for primary cobalt production, highlighting the environmentally-friendly approach of this recycling endeavor.

Unveiling microbial degradation of triclosan: Degradation mechanism, pathways, and catalyzing clean energy.

Emerging organic contaminants present in the environment can be biodegraded in anodic biofilms of microbial fuel cells (MFCs). However, there is a notable gap existing in deducing the degradation mechanism, intermediate products, and the microbial communities involved in degradation of broad-spectrum antibiotic such as triclosan (TCS). Herein, the possible degradation of TCS is explored using TCS acclimatized biofilms in MFCs. 95% of 5 mgL-1 TCS are been biodegraded within 84 h with a chemical oxygen demand (COD) reduction of 62% in an acclimatized-MFC (A-MFC). The degradation of TCS resulted in 8 intermediate products including 2,4 -dichlorophenol which gets further mineralized within the system. Concurrently, the 16S rRNA V3-V4 sequencing revealed that there is a large shift in microbial communities after TCS acclimatization and MFC operation. Moreover, 30 dominant bacterial species (relative intensity >1%) are identified in the biofilm in which Sulfuricurvum kujiense, Halomonas phosphatis, Proteiniphilum acetatigens, and Azoarcus indigens significantly contribute to dihydroxylation, ring cleavage and dechlorination of TCS. Additionally, the MFC was able to produce 818 ± 20 mV voltage output with a maximum power density of 766.44 mWm-2. The antibacterial activity tests revealed that the biotoxicity of TCS drastically reduced in the MFC effluent, signifying the non-toxic nature of the degraded products. Hence, this work provides a proof-of-concept strategy for sustainable mitigation of TCS in wastewaters with enhanced bioelectricity generation.

Techno-environmental analysis to valorize the secondary energy resources from refuse-derived fuel-based waste to energy plant.

The present study quantifies the environmental and sustainability impacts associated with municipal solid waste management (MSWM) in India which plays a vital environmental issue in recent times. The upsurge in population has resulted in massive waste generation, leading to a concerning rise in the level of greenhouse gas (GHG) emissions. Therefore, the sustainable management of MSW has been discussed and highlights the conversion of MSW into refuse-derived fuel (RDF) to identify its potential for generating electricity in waste-to-energy (WtE) plants. The life cycle assessment (LCA) study has been done to identify and compare the environmental impacts associated with different scenarios (SC) as SC1: landfilling without energy recovery, SC2: open burning and SC3: processing of RDF in WtE plant by considering the nine impact categories from the inventory data obtained over a period of 12 consecutive months (Jan 2021-Jan 2022). The results exhibited that the global warming potential caused by emissions of GHG are in the order of SC1 (1188 kg CO2 eq) > SC2 (752 kg CO2 eq) > SC3 (332 kg CO2 eq), respectively from 1 t of MSW. It is concluded that the WtE plant can help in the reduction of environmental issues, strengthening the capacity of electricity generation and improving the aesthetic view of the city which is socially acceptable as well. Thus, WtE technology can help in achieving sustainable development goal 12 to regenerate the sustainable secondary resources for the twenty-first century and minimize global climate change.

Delirious Mania in an Elderly, Challenges in Diagnosis and Treatment.

Delirious mania is an acute neurobehavioral syndrome which can have the features of mania, delirium, psychosis and catatonia. There are no diagnostic and treatment guidelines of delirious mania which can lead to delayed treatment, increasing morbidity and mortality. The primary goal of this report is to raise awareness among healthcare professionals and improve patient outcomes for this potentially life-threatening condition. In this case report, we present an octogenarian female, a case of bipolar disorder, current episode manic, who had impaired orientation, delusion of persecution, and altered sleep-wake cycle. She was treated with a combination of mood stabilizer and antipsychotic and discharged after 24 days of admission.

Levetiracetam-Induced Acute Psychosis in an Adolescent.

Levetiracetam (LEV), a second-generation antiepileptic, is used as an adjunct therapy in primary generalized tonic-clonic seizures, refractory partial-onset seizures, and seizure prophylaxis after brain surgery. It is well tolerated, effective and has a convenient dosing regimen. As any other drugs, it has some adverse drug effects, including neuropsychiatric adverse effects ranging from agitation and mood symptoms to psychosis and suicide. Strong diagnostics guidelines are yet to be formulated for LEV-induced psychosis; however, complete recovery from psychotic symptoms after stopping LEV supports the possible adverse reaction from Naranjo's algorithm and, hence, the diagnosis. This case report presents a 16 years boy with focal onset generalized tonic-clonic seizure, whose drug regimen was switched to LEV, following which he had the delusion of persecution, second-person auditory hallucination, and aggressive behavior, which decreased on the 2nd day of cessation of LEV.

A novel circular approach to analyze the challenges associated with micro-nano plastics and their sustainable remediation techniques.

The mismanagement of consumer-discarded plastic waste (CDPW) has raised global environmental concerns about climate change. The COVID-19 outbreak has generated ∼1.6 million tons of plastic waste per day in the form of personal protective equipment (masks, gloves, face shields, and sanitizer bottles). These plastic wastes are either combustible or openly dumped in aquatic and terrestrial environments. Open dumping upsurges emerging contaminants like micro-nano plastics (MNPs) that directly enter the ecosystem and cause severe impacts on flora and fauna. Therefore, it has become an utmost priority to determine sustainable technologies that can degrade or treat MNPs from the environment. The present review assesses the sources and impacts of MNPs, various challenges, and issues associated with their remediation techniques. Accordingly, a novel sustainable circular model is recommended to increase the degradation efficiency of MNPs using biochemical and biological methods. It is also concluded that the proposed model does not only overcome environmental issues but also provides a sustainable secondary resource to meet the sustainable development goals (SDGs).

Deterministic domain wall rotation in a strain mediated FeGaB/PMN-PT asymmetrical ring structure for manipulating trapped magnetic nanoparticles in a fluidic environment.

The manipulation of domain walls (DWs) in strain-mediated magnetoelectric (ME) heterostructures has attracted much attention recently, with potential applications in precise and location-specific manipulation of magnetic nanoparticles (MNPs). However, the manipulation ability in these structures is restricted to magnetostrictive circular ring structures only, where the required onion state is metastable, less thermally stable, and cannot be obtained easily. This work investigates the highly shape anisotropic FeGaB magnetostrictive elliptical ring structures of different aspect ratios and trackwidths on the PMN-PT piezoelectric substrate to manipulate fluid-borne MNPs using active control of DWs. The proposed model utilizes the attribute that the required onion state in a magnetostrictive elliptical ring is thermally stable and easily obtained compared to magnetostrictive circular ring structures. By varying the trackwidth of elliptical rings, nucleated DWs are rotated at different angles to capture and transport fluid-borne MNPs. Up to a critical trackwidth, DW rotation is predicted by dominant stress anisotropy energy that leads the rotation of DWs and attached MNPs toward the dominant tensile strain direction of PMN-PT with reversibility. Increasing the trackwidth beyond the critical trackwidth caused a complete 90° rotation of DWs and attached MNPs without reversibility and is given by dominant shape anisotropy energy. The fundamental relationship of capture probability with the size and velocity of injected MNPs is also demonstrated. The nucleation and rotation of DWs are predicated using the coupled elastodynamic and electrostatic Finite Difference Method (FDM) micromagnetic model. Dynamics of MNP capture and rotation are envisaged using an analytical model.

Unraveling the Potential Role of Tecomella undulata in Experimental NASH.

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH.

Expression of LIM domain-binding 3 (LDB3), a striated muscle Z-band alternatively spliced PDZ-motif protein in the nervous system.

LIM domain-binding 3 (LDB3) is a member of the Enigma family of PDZ-LIM proteins. LDB3 has been reported as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mechanosensory actin cytoskeleton remodeling. This study shows that LDB3 is broadly expressed in the central and peripheral nervous system of human and mouse. LDB3 is predominantly expressed in the adult stages compared to early development and at a significantly higher level in the spinal cord than in the brain. As in skeletal muscle and heart, LDB3 is extensively alternatively spliced in the neurons. Three novel splice isoforms were identified suggesting splicing-dependent regulation of LDB3 expression in the nervous system. Expression of LDB3 in the motor cortex, cerebellum, spinal motor neuron, peripheral nerve, and neuromuscular junction in addition to skeletal muscle indicates important roles for this PDZ-LIM family protein in motor planning and execution. Moreover, expression in the hippocampal neurons suggests roles for LDB3 in learning and memory. LDB3 interactors filamin C and myotilin are also expressed in the spinal motor neuron, nerve, and neuromuscular junction, thereby providing the basis for neurogenic manifestations in myopathies associated with mutations in these so-called muscle proteins.

AYURAKSHA, a prophylactic Ayurvedic immunity boosting kit reducing positivity percentage of IgG COVID-19 among frontline Indian Delhi police personnel: A non-randomized controlled intervention trial.

Objective: The world continues to face the COVID-19 crisis, and efforts are underway to integrate traditional medicine interventions for its effective management. The study aimed to determine the efficacy of the "AYURAKSHA" kit in terms of post-interventional percentage of COVID-19 IgG positivity, immunity levels, and quality of life (QoL) against COVID-19. Method: This was a non-randomized controlled, prospective intervention trial, done after the distribution of 80,000 AYURAKSHA kits (constituent of Sanshamani Vati, AYUSH Kadha, and Anu Taila) among Delhi police participants in India. Among 47,827 participants, the trial group (n = 101) was evaluated with the positivity percentage of IgG COVID-19 and Immune Status Questionnaire (ISQ) scores as a primary outcome and the WHO Quality of Life Brief Version (QOL BREF) scores along with hematological parameters as a secondary outcome in comparison to the control group (n = 71). Results: The data showed that the percentage of COVID-19 IgG positivity was significantly lower in the trial group (17.5 %) as compared to the control group (39.4 %, p = 0.003), indicating the lower risk (55.6%) of COVID-19 infection in the trial group. The decreased incidence (5.05%) and reduced mortality percentage (0.44%) of COVID-19 among Delhi police officers during peak times of the pandemic also corroborate our findings. The ISQ score and WHO-QOL BREF tool analysis showed the improved scores in the trial group when compared with the controls. Furthermore, no dysregulated blood profile and no increase in inflammation markers like C-reactive protein, erythrocyte sedimentation rate, Interleukin-6 (IL-6) were observed in the trial group. However, significantly enhanced (p = 0.027) IL-6 levels and random blood sugar levels were found in the control group (p = 0.032), compared to a trial group (p = 0.165) post-intervention. Importantly, the control group showed more significant (p = 0.0001) decline in lymphocyte subsets CD3+ (% change = 21.04), CD4+ (% change = 20.34) and CD8+ (% change = 21.54) levels than in trial group, confirming more severity of COVID-19 infection in the control group. Conclusion: The AYURAKSHA kit is associated with reduced COVID-19 positivity and with a better quality of life among the trial group. Hence, the study encourages in-depth research and future integration of traditional medicines for the prevention of the COVID-19 pandemic. Clinical trial registration: http://ctri.nic.in/, identifier: CTRI/2020/05/025171.

Sustainable approach for valorization of solid wastes as a secondary resource through urban mining.

The incessant population has increased the production and consumption of plastics, paper, metals, and organic materials, which are discarded as solid waste after their end of life. The accumulation of these wastes has created growing concerns all over the world. However, conventional methods of solid waste management i.e., direct combustion and landfilling have caused several negative impacts on the environment (releasing toxic chemicals and greenhouse gases, huge land use) besides affecting human health. Therefore, it is requisite to determine sustainable alternative technologies that not only help in mitigating environmental issues but also increase the economic value of the discarded solid wastes. This process is known as urban mining where waste is converted into secondary resources and thereby conserves the natural primary resources. Thus, this review highlights the technological advancements in the valorization process of discarded wastes and their sustainable utilization. We also discussed several limitations of the existing urban mining processes and further the feasibility of valorization techniques was critically analyzed from a techno-economical perspective. This paper recommends a novel sustainable model based on the circular economy concept, where waste is urban mined and recovered as a secondary resource to support the united nations sustainable development goals (SDGs). The implementation of this model will ultimately help the developing countries to achieve the target of SDGs 11, 12, and 14.

Comprehensive technological assessment for different treatment methods of leather tannery wastewater.

The leather-making process necessitates large amounts of water and consequently generates tons of liquid waste as leather tannery wastewater (TWW) is disposed of directly in the open environment. Open disposal of untreated TWW into the natural environment causes an accumulation of various polluting compounds, including heavy metals, dyes, suspended solids inorganic matter, biocides, oils, tannins, and other toxic chemicals. It thus poses potential hazards to the environment and human health. This study primarily focuses on providing in-depth insight into the characteristics, treatment strategies, and regulatory frameworks for managing TWW in leather processing industries. Different technologies of conventional physico-chemical (equalization, coagulation, and adsorption), advanced approaches (Fenton oxidation, ozonation, cavitation), thermo-catalytic and biological treatments available to treat TWW, and their integrative approaches were also highlighted. This review also sheds light on the most frequently applied technologies to reduce contaminant load from TWW though there are several limitations associated with it such as being ineffective for large quantities of TWW, waste generation during treatment, and high operational and maintenance (O&M) costs. It is concluded that the sustainable alternatives applied in the current TWW technologies can minimize O&M costs and recirculate the treated water in the environment. The exhaustive observations and recommendations presented in this article are helpful in the industry to manage TWW and recirculate the water in a sustainable manner.

A comprehensive review on integrative approach for sustainable management of plastic waste and its associated externalities.

The management of post-consumer discarded plastic wastes (PCPW) creates new challenges in developing countries due to the lack of amenities, technological interventions, and associated negative environmental externalities. The fate of untreated recyclable and non-recyclable plastic wastes lies in open dumping along with other solid waste, and improper management leads to environmental externalities such as pollution, global climate change, and health issues. Additionally, open dumping upsurges the emerging microplastics and nano plastics (MNPs) contaminants. The externalities depend on the waste generating sources (household, industries, commercial), waste composition, and its characteristics. However, urban mining can minimize environmental externalities where waste plastics can convert into potential anthropogenic resources and also helps in achieving the target of sustainable development goals (SDGs 11 & 12). Moreover, various treatment technologies that help in the sustainable utilization of plastic wastes are extensively reviewed in this study and evaluate the costs benefits arising during various stages of treating plastic waste through recycling (R), incineration (I), and landfilling (L). The recycling of plastic waste has demonstrated the lowest impact on global warming potential (GWP) and total energy use (TEU), followed by landfilling and incineration (R < L < I). Nevertheless, when energy is recovered from inert (non-recyclable) plastic waste in the form of fuel or by its utilization in construction purposes, the environmental impacts are more negligible (Incineration < Landfilling). Therefore, this study determines the significance of circular economy with legislative approach and standards on plastic waste management, which help in reducing environmental externalities besides yielding a secondary resource as energy and materials through urban mining. A sustainable plastic waste management (SPWM) model is proposed for developing countries to convert plastic waste into resources and use it as a sustainable tool in urban mining.

Study to assess the home-based newborn care (HBNC) visit in rural area of Lucknow: A cross-sectional study.

INTRODUCTION: Home-based newborn care (HBNC) is a strategy adopted by government of India to overcome the burden of newborn deaths in the first week of life, it provides continuum of care for newborn and post-natal mothers. HBNC introduced since 2011 is centred around Accredited Social Health Activist (ASHA) and it is the main community-based approach to newborn health. AIMS AND OBJECTIVES: The objective of the present study was to assess the HBNC during HBNC visit in rural area of Lucknow, Uttar Pradesh (U.P.). MATERIALS AND METHODS: The present cross-sectional study was carried out in the field practice area of Primary Health Centre Sarojini Nagar, Lucknow UP. A total of 200 mothers of newborn (age 03 days to 60 days) born in the catchment area of PHC Sarojini Nagar during 8 months period were included in cross-sectional study. RESULTS: The result of study showed that majority of newborns got all the age appropriate home visit. None of the mothers had knowledge and awareness about the HBNC provision for home visits and the number of home visit by ASHA decreases as age of baby increases. All the ASHAs were aware about the schedule of home visit, the number of home visit in case of home delivery and institutional delivery. CONCLUSION AND RECOMMENDATION: ASHA was found to be the major facilitator for HBNC programme. Knowledge and awareness of ASHA on importance of postnatal care needs to be enhanced via hands on training.

Postnatal newborn care practices and knowledge of newborn danger signs among mothers in rural area of Lucknow, Uttar Pradesh: A cross-sectional study.

INTRODUCTION: The postnatal period is the most critical period for mothers and her newborn especially during the hours and days after birth. Proper utilization of postnatal care services plays a vital role in dropping the maternal mortality ratio and infant mortality rate. METHODS: The community based, cross-sectional study was carried out in the field practice area of Primary Health Centre (PHC) Sarojini Nagar, Lucknow UP. A total of 200 mothers of newborn (age 03 days to 60 days) born in the catchment area of PHC Sarojini Nagar during eight months period were included in this study. A semi-structured pre-tested questionnaire was used for interview of eligible mother. The objective of study was to assess the postnatal newborn care practices and the knowledge of newborn danger sign among mothers in rural area of Lucknow, U.P. RESULTS: The results showed that 49.50% of mothers applied substances to the stump after birth. 52.5% of mothers applied Kajal on the eye of the baby after birth. More than half of the mothers breastfed the baby within 1-4 hours of birth and Exclusive breastfeeding were practiced by nearly half (47%) of the mothers. Less than one-third of mothers used ambulance service 102/108 as their means of transportation to the health facility. CONCLUSION: Unsafe and harmful traditional newborn care practices are more prevalent in the rural areas. Health education and awareness programmes are recommended to improve maternal knowledge on the various aspects of newborn care.

Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation.

Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.

Mutational Spectrum of CAPN3 with Genotype-Phenotype Correlations in Limb Girdle Muscular Dystrophy Type 2A/R1 (LGMD2A/LGMDR1) Patients in India.

BACKGROUND: Limb girdle muscular dystrophy recessive type 1 (LGMDR1, Previously LGMD2A) is characterized by inactivating mutations in CAPN3. Despite the significant burden of muscular dystrophy in India, and particularly of LGMDR1, its genetic characterization and possible phenotypic manifestations are yet unidentified. MATERIAL AND METHODS: We performed bidirectional CAPN3 sequencing in 95 LGMDR1 patient samples characterized by calpain-3 protein analysis, and these findings were correlated with clinical, biochemical and histopathological features. RESULTS: We identified 84 (88.4%) cases of LGMDR1 harboring 103 CAPN3 mutations (71 novel and 32 known). At least two mutant alleles were identified in 79 (94.2%) of patients. Notably, 76% exonic variations were enriched in nine CAPN3 exons and overall, 41 variations (40%) correspond to only eight exonic and intronic mutations. Patients with two nonsense/out of frame/splice-site mutations showed significant loss of calpain-3 protein as compared to those with two missense/inframe mutations (P = 0.04). We observed a slow progression of disease and less severity in our patients compared to European population. Rarely, presenting clinical features were atypical, and mimicked other muscle diseases like FSHMD, distal myopathy and metabolic myopathies. CONCLUSION: This is first systematic study to characterize the genetic framework of LGMDR1 in the Indian population. Preliminary calpain-3 immunoblot screening serves well to direct genetic testing. Our findings prioritized nine CAPN3 exons for LGMDR1 diagnosis in our population; therefore, a targeted-sequencing panel of nine exons could serve well for genetic diagnosis, carrier testing, counseling and clinical trial feasibility study in LGMDR1 patients in India.

Composite Indexing for Nutritional Status Evaluation: A Snapshot of Malnutrition across India.

INTRODUCTION: Data from several sources revealed that huge incongruity persists in nutritional status across the states in India. Thus, this study was undertaken to generate a nutritional index, so that these disparities could be quantified and comparison be done. MATERIALS AND METHODS: A nutritional index for 21 major states of India has been constructed on the basis of eight important nutrition-related indicators. The scaled value of each indicator for all the states was calculated. Each indicator was assigned an arbitrary weight (Wi) on the basis of its impact on nutritional status. On the basis of the scaled value and weight given to the particular indicator, a composite-weighted index was thus calculated. RESULTS: States were ranked on their nutritional status as per the final composite score they attained. Out of 21 major states, Kerala took the top position followed by Jammu and Kashmir and Himachal Pradesh on the 2nd and 3rd position, respectively, while Uttar Pradesh got the lowest rank followed by Bihar and Jharkhand on the 2nd and 3rd lowest positions. CONCLUSION: Our study concludes that not taking an account of the burden of malnutrition when disbursing funds leads to ineffective implementation of various nutritional programs. Integrated Child Development Services has already been brought in mission mode under Poshan Abhiyan. Other determinants, i.e., illiteracy, poor sanitation, diseases, and infections, should also be considered and addressed through nutritional programs.

mTOR pathway activation in focal cortical dysplasia.

BACKGROUND: Focal cortical dysplasia (FCD) is a localized cortical malformation and considerable morphological overlap exists between FCD IIB and neurological lesions associated with Tuberous sclerosis complex (TSC). Abnormal mTOR pathway secondary to somatic mTOR mutation and TSC gene mutation linked to PI3K/AKT/mTOR pathway have supported the hypothesis of common pathogenesis involved. Role of converging pathway, viz. Wnt/ß-Catenin and mTOR is unknown in FCD. We aimed to analyse FCD IIB for TSC1/TSC2 mutations, immunoreactivity of hamartin, tuberin, mTOR and Wnt signalling cascades, and stem cell markers. MATERIALS AND METHODS: Sixteen FCD IIB cases were retrieved along with 16 FCD IIA cases for comparison. Immunohistochemistry was performed for tuberin, hamartin, mTOR pathway markers, markers of stem cell phenotype, and Wnt pathway markers. Mutation analysis for TSC1 and TSC2 was performed by sequencing in 9 FCD cases. RESULTS: All FCD cases showed preserved hamartin and tuberin immunoreactivity. Aberrant immunoreactivity of phospho-P70S6 kinase, S6 ribosomal, phospho-S6 ribosomal and Stat3 was noted in FCD IIB, with variable phospho-4E-BP1 (45%) and absent phospho-Stat3 expression. Immunoreactivity for phospho-P70S6 kinase (100%), S6 ribosomal protein (100%) and Stat3 (100%) was noted in FCD IIA, but not for phospho-S6 ribosomal, phospho-4E-BP1 and phospho-Stat3. c-Myc immunoreactivity was noted in all FCD cases. Nestin (81%) and Sox 2 (88%) stained balloon cells in FCD IIB (44%), while in FCD IIA cases were negative. All FCD cases were immunopositive for Wnt, but were negative for ß-Catenin and cyclin-D1. TSC mutations were detected in two cases of FCD IIB. CONCLUSION: Abnormal mTOR pathway activation exists in FCD IIB and IIA, however, shows differential immunoreactivity profile, indicating varying degrees of dysregulation. Labelling of neuronal stem cell markers in balloon cells suggests they are phenotypically immature. TSC1/2 mutation play role in the pathogenesis of FCD. Deep targeted sequencing is preferred diagnostic technique since conventional sanger sequencing often fails to detect low-allele frequency variants involved in mTOR/TSC pathway genes, commonly found in FCD.

Loss of SMARCB1/INI1 Immunoexpression in Chordoid Meningiomas.

BACKGROUND: Chordoid meningiomas have an aggressive clinical course characterized by frequent recurrences. Recent whole-genome sequencing studies demonstrated Chr22 loss in chordoid meningiomas not accounted for by NF2 mutations. SMARCB1/INI1 is a candidate gene on Chr22, which has not been analyzed extensively in meningiomas. AKT1 mutation has been recently identified to be a driver of meningiomagenesis. MATERIALS AND METHODS: Cases of chordoid meningioma were retrieved along with meningiomas of other subtypes for comparison. INI1 immunohistochemistry was performed. SMARCB1 and AKT1 were analyzed by sequencing. RESULTS: Sixteen chordoid meningiomas were identified (1.1% of all meningiomas). Six cases (37.5%) showed loss of INI1 immunoexpression. All other meningioma subtypes (n = 16) retained INI1 immunoexpression. AKT1 E17K mutation was identified in one case (16.7%). Notably, SMARCB1 mutations were not identified in any of the chordoid meningiomas analyzed, including those showing INI1 loss immunohistochemically. CONCLUSION: This is the first study to demonstrate loss of SMARCB1/INI1 immunoexpression in chordoid meningiomas, adding to the tumors with INI1 loss. However, in absence of INI1 mutation, mechanisms for INI1 loss require further evaluation. Identification of AKT1 mutation opens up new avenues for targeted therapy in patients with such aggressive tumors.