Toxic Epidermal Necrolysis After COVID-19 Vaccination: A Case Report and Review of Literature.

Following vaccination for COVID-19, various cutaneous adverse reactions (CARs) are reported. Here is an Asian male in late 50's who developed necrotic skin with mucosal involvement 10 days following booster dose of ChAdOx1 nCov-19 vaccination. Based on disease course and morphology, toxic epidermal necrolysis (TEN) was suspected. The patient developed respiratory distress and was intubated, intravenous immunoglobulin (IVIG) administered at 2 g/kg body weight following which skin lesions healed in fourth week, the patient was discharged after 50 days of intensive care unit (ICU) stay. Severe CARs are rare following vaccination, of two components in ChAdOx1nCoV-19 adenoviral vector vaccine, virotopes cause T-cell mediated granulysin and granzyme B release leading to epidermal detachment and mucosal involvement of conducting airways causing respiratory failure. CARs can also occur in whom first and second dose was uneventful. Supportive therapy and prevention of sepsis are mainstay of management. Though the use of IVIG has shown conflicting results, our case was successfully managed with IVIG.

Hospitalization Events Among Adolescents and Adults With Sickle Cell Disease in a Tertiary Care Center in Central India.

BACKGROUND: Sickle cell disease (SCD) is an inherited red blood cell disorder, wherein mutation causes the substitution of glutamic acid to valine at the sixth position of the ß-globin chain. These include sickle cell anemia (homozygous sickle mutation), sickle-beta thalassemia, and hemoglobin SCD. The clinical manifestations of SCD are protean. Individuals with SCD suffer from both acute and chronic complications, which include recurring episodes of pain commonly called vaso-occlusive crisis (VOC) - acute chest syndrome (ACS); aseptic necrosis of the bone; micro-infarction of the spleen, brain, and kidney; infections; stroke; and organ damage affecting every part of the body. SCD necessitates frequent hospitalizations because of severe complications, which pose a significant burden on caregivers and economic strain on healthcare systems. The pattern of hospital admission with SCD varies in different parts of the world. OBJECTIVE: This study aimed to determine the causes of hospitalization among adolescent and adult patients with SCD and to determine factors associated with their hospital stay. METHODS: The study was a hospital-based prospective observational study comprising adolescent and adult patients diagnosed with SCD, aged 15-45 years, who were hospitalized in the Department of General Medicine at All India Institute of Medical Sciences in Raipur from August 2021 to August 2022. RESULT: According to our study, the primary reason for hospitalization was a painful crisis, accounting for 63% of cases, followed by infection (17%), ACS (11%), and acute hemolytic crisis (9%). Notably, we did not observe any significant differences between genders and causes of admission (p > 0.05). Joint pain (p = 0.005), back pain (p = 0.001), and chest pain (p = 0.001) were more frequently reported by adults over the age of 19. In addition, our analysis of the duration of hospital stays and various factors revealed that patients admitted for infections had a significantly longer mean hospital stay duration (p = 0.040). CONCLUSION: Acute painful crises were the primary cause of hospital admission among individuals with SCD; many patients also encountered infections and ACS. Furthermore, patients who experienced infections and VOC had a lengthier duration of hospital stay. Therefore, it is essential to provide them with comprehensive instructions on various preventive measures against infections and the factors that trigger painful crises.

Purification, characterization and three-dimensional structure prediction of multicopper oxidase Laccases from Trichoderma lixii FLU1 and Talaromyces pinophilus FLU12.

Broad-spectrum biocatalysts enzymes, Laccases, have been implicated in the complete degradation of harmful pollutants into less-toxic compounds. In this study, two extracellularly produced Laccases were purified to homogeneity from two different Ascomycetes spp. Trichoderma lixii FLU1 (TlFLU1) and Talaromyces pinophilus FLU12 (TpFLU12). The purified enzymes are monomeric units, with a molecular mass of 44 kDa and 68.7 kDa for TlFLU1 and TpFLU12, respectively, on SDS-PAGE and zymogram. It reveals distinct properties beyond classic protein absorption at 270-280 nm, with TlFLU1's peak at 270 nm aligning with this typical range of type II Cu site (white Laccase), while TpFLU12's unique 600 nm peak signifies a type I Cu2+ site (blue Laccase), highlighting the diverse spectral fingerprints within the Laccase family. The Km and kcat values revealed that ABTS is the most suitable substrate as compared to 2,6-dimethoxyphenol, caffeic acid and guaiacol for both Laccases. The bioinformatics analysis revealed critical His, Ile, and Arg residues for copper binding at active sites, deviating from the traditional two His and a Cys motif in some Laccases. The predicted biological functions of the Laccases include oxidation-reduction, lignin metabolism, cellular metal ion homeostasis, phenylpropanoid catabolism, aromatic compound metabolism, cellulose metabolism, and biological adhesion. Additionally, investigation of degradation of polycyclic aromatic hydrocarbons (PAHs) by purified Laccases show significant reductions in residual concentrations of fluoranthene and anthracene after a 96-h incubation period. TlFLU1 Laccase achieved 39.0% and 44.9% transformation of fluoranthene and anthracene, respectively, while TpFLU12 Laccase achieved 47.2% and 50.0% transformation, respectively. The enzyme structure-function relationship study provided insights into the catalytic mechanism of these Laccases for possible biotechnological and industrial applications.

Anthracene detoxification by Laccases from indigenous fungal strains Trichoderma lixii FLU1 and Talaromyces pinophilus FLU12.

The persistence and ubiquity of polycyclic aromatic hydrocarbons (PAHs) in the environment necessitate effective remediation strategies. Hence, this study investigated the potential of purified Laccases, TlFLU1L and TpFLU12L, from two indigenous fungi Trichoderma lixii FLU1 (TlFLU1) and Talaromyces pinophilus FLU12 (TpFLU12), respectively for the oxidation and detoxification of anthracene. Anthracene was degraded with vmax values of 3.51 ± 0.06 mg/L/h and 3.44 ± 0.06 mg/L/h, and Km values of 173.2 ± 0.06 mg/L and 73.3 ± 0.07 mg/L by TlFLU1L and TpFLU12L, respectively. The addition of a mediator compound 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to the reaction system significantly increased the degradation of anthracene, with up to a 2.9-fold increase in vmax value and up to threefold decrease in Km values of TlFLU1L and TpFLU12L. The GC-MS analysis of the metabolites suggests that anthracene degradation follows one new pathway unique to the ABTS system-hydroxylation and carboxylation of C-1 and C-2 position of anthracene to form 3-hydroxy-2-naphthoic acid, before undergoing dioxygenation and side chain removal to form chromone which was later converted into benzoic acid and CO2. This pathway contrasts with the common dioxygenation route observed in the free Laccase system, which is observed in the second degradation pathways. Furthermore, toxicity tests using V. parahaemolyticus and HT-22 cells, respectively, demonstrated the non-toxic nature of Laccase-ABTS-mediated metabolites. Intriguingly, analysis of the expression level of Alzheimer's related genes in HT-22 cells exposed to degradation products revealed no induction of neurotoxicity unlike untreated cells. These findings propose a paradigm shift for bioremediation by highlighting the Laccase-ABTS system as a promising green technology due to its efficiency with the discovery of a potentially less harmful degradation pathway, and the production of non-toxic metabolites.

Analgesic efficacy of stellate ganglion block in head and neck cancer pain: A case series.

Patients with head and neck cancer (HNC) have ongoing pain but Stellate ganglion block which is a sympatholytic block may be a viable therapy for treating it. The data were retrospectively collected from five histopathologically confirmed HNC patients who had completed chemotherapy and radiation doses. Stellate ganglion block was given to these patients and was subsequently monitored for 3 months to assess pain alleviation and overall satisfaction. Over a 3-month period, there was a decrease in the pain levels with a better quality of life so the stellate ganglion block can be a promising modality for reducing the pain of HNC.

Postoperative Delayed Facial Nerve Palsy: A Surgeon's Nightmare.

The facial nerve supplies motor, sensory, and parasympathetic innervation to the head and neck, and its paralysis can have significant physical and psychological impacts. This study discusses a compelling case involving a 21-year-old male who developed delayed facial nerve palsy (DFNP) on the eighth day after cortical mastoid surgery. Through conservative management, the patient achieved a full recovery by the 52nd day. Our experience underscores the importance of approaching DFNP with patience, emphasizing the need for thorough counseling of both the patient and their family members.

Molecular docking analysis of α-Synuclein aggregation with Anle138b.

α-Synuclein aggregation into toxic oligomeric species is central to Parkinson's disease pathogenesis. Anle138b is a recently identified inhibitor of α-synuclein oligomerization showing promise in preclinical studies. This study employed computational approaches to elucidate Anle138b's mechanism of oligomer-specific action. The inhibitory potential of Anle138b against α-synuclein oligomers was evaluated by performing molecular docking studies using AutoDock Tools, followed by their binding pocket analysis. Further, protein-protein docking studies were performed using Hex8.0 to validate the aggregation inhibitory potential of Anle138b. Molecular docking revealed increasing binding affinity of Anle138b against higher order α-synuclein oligomers (dimer to decamer). Anle138b occupied oligomeric cavity and interacted with residues Thr54, Gly73, Val74 and Thr75 across several oligomers. Protein-protein docking showed that Anle138b interferes with α-synuclein decamer formation. These results highlight the oligomer-directed inhibitory mechanism of Anle138b, without hindering the monomeric forms and provide molecular insights to advance its therapeutic development for Parkinson's and related synucleinopathies.

Molecular docking analysis of marine compounds with voltage gated calcium channel for potential anti-epileptic molecules.

Epileptic seizures are directly linked with an anomalous influx of extracellular calcium or sodium anions through voltage-gated channels disturb the chemical and electrical gradients, resulting in seizures or jerking moments. Voltage-gated calcium channel (VGCC) subunit α2δ-1 is the binding site for gabapentinoids used to treat epilepsy and neuropathic pain. However, this class of drugs showed severe side effects associated with CNS and respiratory depression. Hence, we screened a total of 2583 phytochemicals from the Comprehensive Marine Natural Products Database for their drug likeliness and pharmacokinetics (ADME/T) properties. The selected phytochemicals were docked with the VGCC α2δ-1 protein target and the marketed AED Pregabalin is used as standard. The docking results helped to select 45 docked compounds with better binding affinity, among which Acanthiline A showed the maximum binding affinity with the binding energy of -11.9 kcal/mol, thus reflecting its potential anti-epileptic activity.

Comparison between perfusion index, pleth variability index, and pulse pressure variability for prediction of hypotension during major abdominal surgery under general anaesthesia: A prospective observational study.

Background and Aims: Short-term hypotension after general anaesthesia can negatively impact surgical outcomes. This study compared the predictive potential of the pleth variability index (PVI), pulse pressure variability (PPV), and perfusion index (PI) for anaesthesia-induced hypotension. This study's primary objective was to evaluate the predictive potential of PI, PVI, and PPV for hypotension. Methods: This observational study included 140 adult patients undergoing major abdominal surgery under general anaesthesia. Mean arterial pressure, heart rate, PVI, PPV, and PI were collected at 1-min intervals up to 20 min post anaesthesia induction. Hypotension was assessed at 5-min and 15-min intervals. Receiver operating characteristic (ROC) curves were plotted to determine the diagnostic performance and best cut-off for continuous variables in predicting a dichotomous outcome. Statistical significance was kept at P < 0.05. Results: Hypotension prevalence within 5 and 15 min of anaesthesia induction was 36.4% and 45%, respectively. A PI cut-off of <3.5 had an area under the ROC curve (AUROC) of 0.647 (P = 0.004) for a 5-min hypotension prediction. The PVI's AUROC was 0.717 (P = 0.001) at cut-off >11.5, while PPV's AUROC was 0.742 (P = 0.001) at cut-off >12.5. At 15 min, PVI's AUROC was 0.615 (95% confidence interval 0.521-0.708, P = 0.020), with 54.9% positive predictive value and 65.2% negative predictive value. Conclusion: PVI, PPV, and PI predicted hypotension within 5 min after general anaesthesia induction. PVI had comparatively higher accuracy, sensitivity, specificity, and positive predictive value than PI and PPV when predicting hypotension at 15 min.

Population genetics of the critically endangered three-striped turtle, Batagur dhongoka, from the Ganga river system using mitochondrial DNA and microsatellite analysis.

The three-striped roofed (Batagur dhongoka) is a semi-aquatic turtle that belongs to family Geoemydidae. Due to anthropogenic pressure, it has been facing an intense decline of over 80% in its distribution range in the past 50 years. It is considered as 'Critically Endangered' so effective conservation strategies are needed to protect the species by determining their genetic diversity and population genetic structure. This study investigates the genetic diversity, population structure and demographic pattern of B. dhongoka from two Turtle Rescue and Rehabilitation Centre established near Ganga river using mitochondrial cytochrome b (Cyt b: 1140 bp) ; control region (CR: 451 bp) and ten nuclear microsatellite loci. mtDNA results show low levels of nucleotide diversity (π = 0.0022) in B. dhongoka haplotypes and provide evidence for a low substitution rate. The demographic pattern estimated by the Bayesian skyline plot (BSP) analysis indicates historical stability followed by growth in the effective population size, with a recent reduction in population size from ~ 2 thousand years ago. The microsatellite findings show a moderate level of observed heterozygosity (Ho: 0.49). Bayesian-based clustering analysis revealed weak genetic structures in B. dhongoka and presence of admixed assignations suggesting close genetic relationships. These findings shed light on B. dhongoka's genetic status and underline the necessity of comprehensive rehabilitation and relocation programs and conservation and management techniques to ensure the species' long-term survival. In order to ensure the effective protection and conservation of B. dhongoka, the Government of India has taken a proactive measure by incorporating it into Schedule I of the Wildlife (Protection) Act, 1972, as amended in 2022.

Effect of Enhanced Recovery after Surgery (ERAS) protocol on maternal outcomes following emergency caesarean delivery: A randomized controlled trial.

Background: With ever increasing rates of emergency caesarean deliveries (CD),incorporating the ERAS protocol might provide a perfect window of opportunity to increase maternal comfort during the postsurgical period, but also improve outcomes and facilitate optimal return of physiological function. Objective: To determine whether an ERAS pathway at emergency caesarean birth would permit a reduction in postoperative length of stay and improve postoperative patient satisfaction. Material & methods: Patients undergoing emergent caesarean delivery at ≥ 34 weeks of gestation were randomized to ERAS or conventional care. The primary outcome was to compare postoperative length of hospital stay. Secondary outcome variables included first oral intake, passage of flatus/defecation, first ambulation, first urination after catheter removal and postoperative pain scores in both groups. Results: We randomized 142 women (71 each in ERAS versus Conventional arm) undergoing emergency cesarean delivery. Incorporation of ERAS protocol resulted in shorter length of hospital stay (73.92 ± 8.96 in conventional arm vs 53.87 ± 15.02 in ERAS arm; p value <.0001). Significant difference was seen in visual analogue scoring during initial ambulation and rest on day 0 and day 1 between ERAS and conventional arms with mean scores being lower in ERAS arm compared to Conventional arm (p value <.05). In terms of quality of life, ERAS arm had better quality of life compared to conventional arm. Conclusion: Incorporation of ERAS protocol in emergency caesarean definitely improves patient outcome in terms of early resumption of activities with better quality of life.

Molecular docking analysis of marine phytochemicals with BACE-1.

Alzheimer's disease (AD), a debilitating neurodegenerative condition, is characterized by progressive cognitive decline brought about by the deposition of amyloid beta (Aß) plaques in the brain initiates downstream neuronal dysfunction and death in AD pathogenesis. The ß-secretase (BACE-1) enzyme plays a crucial role in generating Aß from amyloid precursor protein (APP). Hence, we report the virtual screening of marine phytochemicals as BACE-1 inhibitors. 2583 compounds, retrieved from Comprehensive Marine Natural Product Database (CMNPD), were primarily screened for drug-likeliness and blood-brain barrier permeability using admetSAR 2.0 and in-house BBBper tool and resulted in a total of 635 phytochemicals, selected for further docking studies using BACE-1 as target receptor and Atabecestat as standard BACE-1 inhibitor. Seven of 635 compounds docked against BACE-1, showed better binding affinities than Atabecestat, with the red algal metabolite lactodehydrothyrsiferol showing lowest binding energy of -10.83 kcal/mol. These compounds are worth investigating further to assess their neuroprotective efficacy and pharmacokinetic properties. The study also provides a rational framework to uncover novel pharmacophores from marine sources for AD therapy acting through BACE-1 inhibition.

Insights into amyloid precursor protein target through PPI network analysis.

Alzheimer's disease (AD) is the leading cause of dementia worldwide with therapeutic lacunae till date. The beta-amyloid (Aß) accumulation triggers AD pathogenesis, though clinical trials lowering Aß have not altered disease outcomes suggesting other interacting factors to be identified for drug design of AD. Therefore, it is of interest to identify potential hub proteins interlinked with disease-driving pathways using a network-based approach for AD therapeutic designing. Literature mining was done to identify proteins implicated in AD etiology. Protein-protein interactions (PPIs) were retrieved from the STRING database and merged into a single network using Cytoscape 3.10.1. The hub proteins involved in AD etiology were predicted based on the topological algorithms of CytoHubba. Six major proteins, with STRING database identifiers - APP, BACE1, PSEN1, MAPT, APOE4 and TREM2, were identified to be involved in AD pathogenesis. The merged network of PPIs of these proteins contained 51 nodes and 211 edges, as predicted by Analyzer module of Cytoscape. The Amyloid precursor protein (APP) emerged as the highest-scoring hub protein across multiple centrality measures and topological algorithms. Thus, current data provides evidence to support the ongoing investigation of APP's multifaceted functions and therapeutic potential for AD.

Genetic diversity, spatial connectivity, and population structure of Asian silurid catfish Wallago attu (Bloch and Schneider, 1801) in the Ganga River System: insights from mitochondrial DNA analysis.

BACKGROUND: The Ganga River System (GRS) is a biodiversity hotspot, its ecological richness is shaped by a complex geological history. In this study, we examined the genetic diversity, spatial connectivity, and population structure of the Asian Silurid catfish, Wallago attu, across seven tributaries of the GRS. METHODS AND RESULTS: We employed three mitochondrial DNA (mtDNA) regions: cytochrome c oxidase subunit I (COXI), cytochrome b (Cyt b), and control region (CR). Our comprehensive dataset encompassed 2420 bp of mtDNA, derived from 176 W. attu individuals across 19 sampling sites within the seven rivers of GRS. Our findings revealed high gene diversity (Hd:0.99) within W. attu populations. Analysis of Molecular Variance (AMOVA) highlighted that maximum genetic variations were attributed within the populations, and the observed genetic differentiation among the seven populations of W. attu ranged from low to moderate. Network analysis uncovered the presence of three distinct genetic clades, showing no specific association with seven studied rivers. Bayesian skyline plots provided insights into the demographic history of W. attu, suggesting a recent population expansion estimated to have occurred approximately 0.04 million years ago (mya) during the Pleistocene epoch. CONCLUSIONS: These results significantly enhance our understanding of the genetic diversity and spatial connectivity of W. attu, serving as a vital foundation for developing informed conservation strategies and the sustainable management of this economically valuable resource within the Ganga River System.

Mechanical Properties, Microstructure, and Actuation Behavior of Wire Arc Additive Manufactured Nitinol: Titanium Bimetallic Structures.

Nitinol (NiTi) is well known for its corrosion resistance, shape memory effect, superelasticity, and biocompatibility, whereas Titanium (Ti) is well known for its high specific strength, corrosion resistance, and biocompatibility. The bimetallic joint of NiTi and Ti is required for applications that require tailored properties at different locations within the same component, as well as to increase design flexibility while reducing material costs. However, because of the formation of brittle intermetallic phases, connecting NiTi and Ti is difficult. In the present study, a systematic experimental investigation is carried out to develop NiTi-Ti bimetallic joint using wire arc additive manufacturing (WAAM) for the first time and to evaluate its microstructure, mechanical properties, martensitic transformation, and actuation behavior in the as-built condition. The defect-free joint is obtained through WAAM and microstructural studies indicate the formation of intermetallics at the NiTi-Ti interface leading to higher microhardness values (600 HV). Shape recovery behavior and phase transformation temperature were also enhanced in comparison to NiTi. An improved actuation and bending angle recovery is observed in comparison with NiTi. The present study lays the way for the use of WAAM in the construction of NiTi and Ti bimetallic structures for engineering and medicinal applications.

Decoding the structural integrity and multifunctional role of Era protein in the survival of Mycobacterium tuberculosis H37Rv.

Era, a widely known GTP binding protein found in many organisms including prokaryotes and eukaryotes and plays a significant role in many fundamental cellular processes like cell growth, differentiation and signaling. In Mycobacterium tuberculosis (Mtb) H37Rv, Era protein had been proved as a GTPase protein but its structural and functional insights are still lacking. Through comparative analysis, structural modeling, docking and using various bioinformatic tools, a detailed investigation of Era was carried out to deduce the structure, function and residues involved in the activity of the protein. Intriguingly, docking results revealed high binding affinity of Era not only with GTP but also with ATP. Myristoylation modifications and phosphorylations on Era were predicted to possibly aid in regulating Era activity and localization; and also the role of Era in translation regulation was foreseen by showing its association with 16s rRNA. Moreover, point mutation of Era residues revealed the effect of W288G and K19G in highly destabilizing the protein structure and activity. Additionally, Era protein was docked with 25 GTPase/ATPase inhibitors, where, Dynasore inhibitor showed the highest affinity for the protein's GTP binding sites and can be used for further drug trials to inhibit growth of mycobacteria.Communicated by Ramaswamy H. Sarma.

MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding.Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis.Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively.Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra.

Mobile and Computer-Based Applications for Rehabilitation Monitoring and Self-Management After Knee Arthroplasty: Scoping Review.

BACKGROUND: Successful post-knee replacement rehabilitation requires adequate access to health information, social support, and periodic monitoring by a health professional. Mobile health (mHealth) and computer-based technologies are used for rehabilitation and remote monitoring. The extent of technology use and its function in post-knee replacement rehabilitation care in low and middle-income settings are unknown. OBJECTIVE: To inform future mHealth intervention development, we conducted a scoping review to map the features and functionality of existing technologies and determine users' perspectives on telerehabilitation and technology for self-management. METHODS: We followed the Joanna Briggs Institute methodology for scoping reviews. We searched the Embase, Medline, PsycINFO via OVID, and Cochrane Central Register of Controlled Trials databases for manuscripts published from 2001 onward. We included original research articles reporting the use of mobile or computer-based technologies by patients, health care providers, researchers, or family members. Studies were divided into the following 3 categories based on the purpose: validation studies, clinical evaluation, and end user feedback. We extracted general information on study design, technology features, proposed function, and perspectives of health care providers and patients. The protocol for this review is accessible in the Open Science Framework. RESULTS: Of the 5960 articles, 158 that reported from high-income settings contributed to the qualitative summary (64 studies on mHealth or telerehabilitation programs, 28 validation studies, 38 studies describing users' perceptions). The highest numbers of studies were from Europe or the United Kingdom and North America regarding the use of a mobile app with or without wearables and reported mainly in the last decade. No studies were from low and middle-income settings. The primary functions of technology for remote rehabilitation were education to aid recovery and enable regular, appropriate exercises; monitoring progress of pain (n=19), activity (n=20), and exercise adherence (n=30); 1 or 2-way communication with health care professionals to facilitate the continuum of care (n=51); and goal setting (n=23). Assessment of range of motion (n=16) and gait analysis (n=10) were the commonly validated technologies developed to incorporate into a future rehabilitation program. Few studies (n=14) reported end user involvement during the development stage. We summarized the reasons for satisfaction and dissatisfaction among users across various technologies. CONCLUSIONS: Several existing mobile and computer-based technologies facilitate post-knee replacement rehabilitation care for patients and health care providers. However, they are limited to high-income settings and may not be extrapolated to low-income settings. A systematic needs assessment of patients undergoing knee replacement and health care providers involved in rehabilitation, involving end users at all stages of development and evaluation, with clear reporting of the development and clinical evaluation can make post-knee replacement rehabilitation care in resource-poor settings accessible and cost-effective.

Immunoinformatics approaches in developing a novel multi-epitope chimeric vaccine protective against Saprolegnia parasitica.

Saprolegnia parasitica is responsible for devastating infections in fish and poses a tremendous threat to the global aquaculture industry. Presently, no safe and effective control measures are available, on the contrary, use of banned toxic compounds against the pathogen is affecting humans via biomagnification routes. This pioneering study aims to design an effective multi-epitope multi-target vaccine candidate against S. parasitica by targeting key proteins involved in the infection process. The proteins were analyzed and linear B-cell epitopes, MHC class I, and class II epitopes were predicted. Subsequently, highly antigenic epitopes were selected and fused to a highly immunogenic adjuvant, 50S ribosomal protein L7/L12, to design a multi-epitope chimeric vaccine construct. The structure of the vaccine was generated and validated for its stereochemical quality, physicochemical properties, antigenicity, allergenicity, and virulence traits. Molecular docking analyses demonstrated strong binding interactions between the vaccine and piscine immune receptors (TLR5, MHC I, MHC II). Molecular dynamics simulations and binding energy calculations of the complexes, further, reflected the stability and favorable interactions of the vaccine and predicted its cytosolic stability. Immune simulations predicted robust and consistent kinetics of the immune response elicited by the vaccine. The study posits the vaccine as a promising solution to combat saprolegniasis in the aquaculture industry.

Clinical side-effects based drug repositioning for anti-epileptic activity.

Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the 'dplyr' package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-ß1 (GABAr α1-ß1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-ß1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication.Communicated by Ramaswamy H. Sarma.

Identification of gene signature markers in gestational hypertension and early-onset pre-eclampsia.

INTRODUCTION: Hypertensive disorders in pregnancy (HDP) are the leading cause of perinatal mortality worldwide. Inflammatory responses induced by insufficient placental perfusion have become a focal point in understanding the pathogenesis and aetiology of HDP and developing reliable and consistent biomarkers. Therefore, this study aims to identify gene signatures linked to the pathophysiology of HDP (gestational hypertension and early and late-onset pre-eclampsia). METHODS: RNA was extracted from the maternal serum from the blood samples collected from different groups of HDP patients. A multiplex inflammation panel (255 inflammatory and housekeeping genes) and further gene expression analysis using NanoString Digital Direct Detection were done. The prominent expressions of these genes were further validated through qPCR techniques. RESULTS: NanoString analysis identified nine unique, significantly expressed genes (MAPK1, MAPK3, MAFF, HLA-DRA, IL12B, RHOA, MASP2, MEF2A and NR3C1) between specific group comparisons of different HPD classes and the normotensive groups. The qPCR showed that the HLA-DRA gene was significantly upregulated in the early-onset pre-eclamptic and gestational hypertensive group compared to its respective normotensive group. In contrast, MAFF and MEF2A were significantly downregulated in both HDPs compared to their controls. The MAPK1 gene was significantly higher in the early-onset group compared to the gestational hypertensive and normotensive groups. DISCUSSION: The upregulation of these distinctive genes in hypertensive groups compared to normotensives confirmed their diagnostic potential. Therefore, HLA-DRA, MAFF and MEF2A could be candidate markers of HDP, while the MAPK1 gene could be a differentiating marker between early-onset pre-eclampsia and gestational hypertension.