Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope.

Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold-Jarisch reflex (BJR), first described2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses-hypotension, bradycardia and suppressed respiration-and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.

Influence of different types of explants in chickpea regeneration using thidiazuron seed-priming.

A comparative regeneration of three types of explants prepared from axillary meristems, plumular apices and hypocotyls of chickpea (Cicer arietinum) was carried out using four thidiazuron (TDZ) treatment methods. The first and third ones included the short-term 20 µM TDZ pre-treatment for all three explant types followed by non-supplementation or supplementation of TDZ (4 µM) into the shoot induction medium (SIM), while the second and fourth ones lacked TDZ pre-treatment followed by non-addition or addition of 4 µM TDZ in the SIM. Axillary meristem explants produced the best results with seed pre-treatment using 20 µM TDZ without TDZ in SIM and showed the highest rate of regeneration efficiency (71.33 ± 1.5%) after 20 days. Concurrently, plumular apex explants from TDZ-primed seeds was ranked second, exhibiting a regeneration percentage of 54.33 ± 2.3% in SIM without supplementation of TDZ, whereas explants from hypocotyls generated from seeds subjected to any of the TDZ treatments were not regenerated on any SIMs after 20 days.

Acylation of oxindoles using methyl/phenyl esters via the mixed Claisen condensation - an access to 3-alkylideneoxindoles.

Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources, viz. methyl and phenyl esters, which acylate oxindoles via the mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples of ortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.

Effects of Heat stress and molecular mitigation approaches in orphan legume, Chickpea.

Global warming has an adverse impact on agriculture and food security is in doldrums around the world. A sharp increase in the temperature of earth is expected and may lead to ~ 1.8-4 °C rise in average earth temperature by the year 2100. Thus, heat stress is a critical factor for plant growth development and crop yield. Chickpea, which is an important leguminous crop and rich source of proteins is also a heat sensitive crop but high temperature exceeding 35 °C inhibit its productivity. Climate-smart agriculture seems to be a plausible approach to minimize the drastic effect of climate change on plant's adaptation. This may help in better selection of tolerant cultivars of chickpea that can be used in breeding programmes for heat stress tolerance in chickpea. Also the biotechnological approaches using candidate genes expressed in transgenics plants may play pivotal role in the production of climate resilient chickpea plants. Some preliminary findings using CAP2, Galactinol synthase genes, proteomic approaches, RNA seq data, stay green traits and -OMICS in general, have proved to be promising. A close collaboration between agronomists, plant physiologists, geneticists, biotechnologists is the pressing need and must be envisioned in order to address heat stress tolerance in chickpea under the prevailing climatic conditions and continuously increasing temperature. In the context of global heat stress and climate change, adaptation and mitigation are the keywords for employing transdisciplinary methodologies with respect to plant growth, development and agronomy.

Plant growth promoting Pseudomonas aeruginosa from Valeriana wallichii displays antagonistic potential against three phytopathogenic fungi.

The soil nature and characterstics are directly related to the micro-organisms present, bio-mineralization process, plant type and thus having harmonius and interdependent relationships. Soil bacteria having antagonistic activity against phytopathogens, play an important role in root growth, overall plant growth and also their composition depends upon the plant species. Population explosion across globe has resulted in indiscriminate use of chemical fertilizers, fungicides and pesticides, thus posing serious risk to plant productivity and soil flora. Plant growth promoting rhizobacteria (PGPRs) are considered safer than chemical fertilizers as they are eco-friendly and sustain longer after colonization in rhizospheric soil. PGPRs are preferred as a green choice and acts as a superior biocontrol agents against phytopathogens. In the present study, a potential rhizobacteria, Pseudomonas aeruginosa (isolate-2) was isolated from the rhizosphere of a medicinal plant, Valeriana wallichi. The bacterial isolate exhibited qualitative tests for plant growth promoting determinatives. It was also subjected to in-vitro biocontrol activity against potential phytopathogens viz. Alternaria alternata, Aspergillus flavus and F. oxysporum. The antagonistic efficacy against F. oxysporum was 56.2% followed by Alternaria alternata to be 51.02%. The maximum inhibition of radial growth of F. oxysporum was 69.2%, Alternaria alternata (46.4%) and Aspergillus flavus (15%). The Pseudomonas aeruginosa exhibited plant growth promotion rhizobacterial activity which can be expoited as biofertilizers. This study deals with microbial revitalization strategy and offers promising solution as a biocontrol agent to enhance crop yield. Further, PGPRs research using the interdisciplinary approaches like biotechnology, nanotechnology etc. will unravel the molecular mechanisms which may be helpful for maximizing its potential in sustainable agriculture.

Promising Roles of Alternative Medicine and Plant-Based Nanotechnology as Remedies for Urinary Tract Infections.

Urinary tract infections (UTIs) are considered to be the most common infections worldwide, having an incidence rate of 40-60% in women. Moreover, the prevalence of this disorder in adult women is 30 times more than in men. UTIs are usually found in many hospitals and clinical practice; as disorders, they are complicated and uncomplicated; in uncomplicated cases, there is no structural or functional abnormality in the urogenital tract. However, obstruction, retention of urine flow and use of catheters increase the complexity. There are several bacteria (e.g., E. coli, Klebsiella pneumoniae, Proteus vulgaris, etc.) successfully residing in the tract. The diagnosis must not only be accurate but rapid, so early detection is an important step in the control of UTIs caused by uropathogens. The treatment of UTIs includes appropriate antimicrobial therapy to control the infection and kill the causal microbes inside the body. A long-time usage of antibiotics has resulted in multidrug resistance causing an impediment in treatment. Thus, alternative, combinatorial medication approaches have given some hope. Available treatments considered Homeopathic, Ayurvedic, Unani, and other herbal-based drugs. There are new upcoming roles of nanoparticles in combating UTIs which needs further validation. The role of medicinal plant-based nanotechnology approaches has shown promising results. Therefore, there must be active research in phyto-based therapies of UTIs, such as Ayurvedic Biology.

Benzothiophenes as Potent Analgesics Against Neuropathic Pain.

Neuropathic pain arises because of neuronal injury. Unlike inflammatory pain which can be managed by classical nonsteroid anti-inflammatory drugs (NSAIDs), neuropathic pain is difficult to treat. The classical NSAIDs work through inhibition of cyclooxygenase 2 (COX2) enzyme. However, COX2 inhibitors are insufficient to treat neuropathic pain. Hence, it becomes important to explore for novel molecules acting through cell surface molecules like ion channels, for the treatment of neuropathic pain. We investigated multiple bromobenzothiophene carboxamides for their efficacy against neuropathic pain. Interestingly, AS6 was found to be very effective in treating neuropathic pain through inhibition of Kv4.3 ion channel. AS6 also reduced the COX2 overexpression associated with neuropathic pain. These results as well as results from our previous study indicate that AS6 can be a potent antinociceptive agent against both inflammatory and neuropathic pain.

Association of TERT-CLPTM1L and 8q24 Common Genetic Variants with Gallbladder Cancer Susceptibility and Prognosis in North Indian Population.

Gallbladder carcinoma (GBC) is one of the common malignancy of the biliary tract. Several genome wide and candidate gene studies have reported associations between multiple cancer types and single-nucleotide polymorphisms on 5p15.33 and 8q24.21 loci. However, predisposition potential of these genetic variants has not been assessed in GBC. We performed the present study to assess the potential of five polymorphisms on 5p15.33 and one on 8q24.21 locus in GBC risk and treatment response in patients undergoing chemoradiotherapy. We extracted genomic DNA from peripheral blood and genotyped selected SNPs using TaqMan allelic discrimination assays in 523 GBC cases and 274 controls from the north-Indian population. Statistical tests were performed to assess the association of selected common genetic variants with gallbladder cancer susceptibility and prognosis. Binary logistic regression analysis showed significant association of TERT rs2736100C > A [OR(CI) = 0.690(0.515-0.924), p value = 0.013], CLPTM1L rs401681C > T [OR(CI) = 0.586(0.405-0.847), p value = 0.004], and CASC8 rs6983267G > T [OR(CI) = 1.629(1.215-2.186), p value = 0.001] with GBC risk. Further, using multivariate logistic regression, we observed that haplotype CLPTM1L Crs401681Crs31489 TERT Trs2853676Ars2736100 MIR4457 Grs4635969 [OR(CI) = 7.52 (1.79-31.52), p value = 0.0064] is significantly associated with poor treatment response. In survival analysis, Kaplan-Meier survival curves showed significantly poor survival and COX regression suggested significantly higher hazard ratio in TT genotype carriers of CASC8 rs6983267 [OR(CI) = 4.28(1. 07-17.10), p value = 0.040] as compared to major allele and heterozygous (GG+GT) genotypes in metastatic GBC cases. The study revealed that 5p15.33 and 8q24.21 genetic variants significantly influence GBC risk and treatment response in north-Indian population.

Riboswitch regulation in cyanobacteria is independent of their habitat adaptations.

Cyanobacteria are one of the ancient bacterial species occupying a variety of habitats with diverse metabolic preferences. RNA regulators like riboswitches play significant role in controlling the gene expression in prokaryotes. The taxonomic distribution of riboswitches suggests that they might be one of the oldest mechanisms of gene control system. In this paper, we analyzed the distribution of different riboswitch families in various cyanobacterial genomes. It was observed that only four riboswitch classes were abundant in cyanobacteria, B12-element (Cob)/AdoCbl/AdoCbl-variant riboswitch being the most abundant. The analysis suggests that riboswitch mode of regulation is present in cyanobacterial species irrespective of their habitat types. A large number of unidentified genes regulated by riboswitches listed in this analysis indicate the wide range of targets for these riboswitch families. The analysis revealed a large number of genes regulated by riboswitches which may assist in elaborating the diversity among the cyanobacterial species.

Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.

BACKGROUND: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer. METHODS: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20-80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20-80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association. FINDINGS: The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8 × 10-9; replication p=0·01; combined p=2·3 × 10-10); rs17209837 (GWAS p=2·0 × 10-8; replication p=0·02; combined p=2·3 × 10-9), and rs4148808 (GWAS p=2·4 × 10-8; replication p=0·008; combined p=2·7 × 10-9). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30-1·66; p=2·31 × 10-10) for rs1558375, 1·61 (1·38-1·89; p=2·26 × 10-9) for rs17209837, and 1·57 (1·35-1·82; p=2·71 × 10-9) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 [95% CI 1·80-5·49]). INTERPRETATION: To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4, underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer. FUNDING: The Tata Memorial Centre and Department of Biotechnology.

Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival.

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract with adverse prognosis and poor survival. Wnt signaling plays an important role in embryonic development and regeneration of tissues in all the species. Deregulation of expression and mutations in this pathway may lead to disease state such as cancer. In this study, we assessed the association of common germline variants of Wnt pathway genes (SFRP2, SFRP4, DKK2, DKK3, WISP3, APC, ß-catenin, AXIN-2, GLI-1) to evaluate their contribution in predisposition to GBC and treatment outcomes. The study included 564 GBC patients and 250 controls. Out of 564, 200 patients were followed up for treatment response and survival. Tumor response (RECIST 1.1) was recorded in 116 patients undergoing non-adjuvant chemotherapy (NACT). Survival was assessed by Kaplan-Meier curve and Cox-proportional hazard regression. Single locus analysis showed significant association of SFRP4 rs1802073G > T [p value = 0.0001], DKK2 rs17037102C > T [p value = 0.0001], DKK3 rs3206824C > T [p value = 0.012], APC rs4595552 A/T [p value = 0.021], APC rs11954856G > T [p value = 0.047], AXIN-2 rs4791171C > T [p value = 0.001], ß-catenin rs4135385A > G [p value = 0.031], and GLI-1 rs222826C > G [p value = 0.001] with increased risk of GBC. Gene-gene interaction using GMDR analysis predicted APC rs11954856 and AXIN2 rs4791171 as significant in conferring GBC susceptibility. Cox-proportional hazard model showed GLI-1 rs2228226 CG/GG and AXIN-2 rs4791171 TT genotype higher hazard ratio. In recursive partitioning, AXIN-2 rs4791171 TT genotype showed higher mortality and hazard. Most of studied genetic variants influence GBC susceptibility. APC rs11954856, GLI-1 rs2228226, and AXIN-2 rs4791171 were found to be associated with poor survival in advanced GBC patients.

Effect of Nanohexaconazole on Nitrogen Fixing Blue Green Algae and Bacteria.

Nanohexaconazole is a highly efficient fungicide against Rhizoctonia solani. Nanoparticles are alleged to adversely affect the non-target organisms. In order to evaluate such concern, the present study was carried out to investigate the effect of nanohexaconazole and its commercial formulation on sensitive nitrogen fixing blue green algae (BGA) and bacteria. Various activities of algae and bacteria namely growth, N-fixation, N-assimilation, Indole acetic acid (IAA) production and phosphate solubilization were differently affected in the presence of hexaconazole. Although, there was stimulatory to slightly inhibitory effect on the growth measurable parameters of the organisms studied at the recommended dose of nanohexaconazole, but its higher dose was inhibitory to all these microorganisms. On the other hand, the recommended as well as higher dose of commercial hexaconazole showed much severe inhibition of growth and metabolic activity of these organisms as compared to the nano preparation. The uses of nanohexazconazole instead of hexaconazole as a fungicide will not only help to control various fungal pathogens but also sustain the growth and activity of these beneficial microorganisms for sustaining soil fertility and productivity.

Evaluation of benzothiophene carboxamides as analgesics and anti-inflammatory agents.

Nonsteroid anti-inflammatory drugs (NSAIDs) represent standard therapy for the alleviation of pain and inflammation. At present various classes of compounds have been reported as selective inhibitors of cyclooxygenase-2 (COX-2). However, they are associated with adverse side effects. To address these issues, we report here a new class of compounds that exhibit potent analgesic and anti-inflammatory response. Substituted bromo-benzothiophene carboxamides (4-11) were examined for their analgesic and anti-inflammatory properties. Our findings demonstrate that newly synthesized bromo-benzothiophene carboxamide derivatives 4, 6, and 8 attenuate nociception and inflammation at lower concentration than classical NSAIDs, such as ibuprofen. These compounds act by selectively inhibiting COX-2 and by disrupting the prostaglandin-E2-dependent positive feedback of COX-2 regulation, which was further substantiated by reduction in the levels of cytokines, chemokines, neutrophil accumulation, synthesis of prostaglandin-E2, expression of COX-2, and neutrophil activation at lower concentration than the classic NSAID ibuprofen. Toxicological study reveals that these compounds are well tolerated and metabolized to avoid any toxicity. Thus, these molecules represent a new class of analgesic and anti-inflammatory agents. © 2014 IUBMB Life, 66(3):201-211, 2014.

Biofilm forming, exopolysaccharide producing and halotolerant, bacterial consortium mitigates salinity stress in Triticum aestivum.

Biofilm and EPS characterization of a rhizobacterial isolate BC-II-20 was done using biophysical techniques. SEM revealed surface morphology of EPS powder to be irregular porous web-like structure. FTIR spectra showed peaks of the polymeric carbohydrate functional groups with probable role in imparting biological properties to EPS. XRD analysis showed signal at 220 (2θ) and confirms its amorphous or semi-crystalline nature. EPS derived from bacterial consortium gradually increased under 200 mM, 400 mM, 600 mM and 800 mM NaCl and SEM-EDAX analysis of EPS showed increase in Na & Cl peaks under the above salt concentrations, depicting EPS-NaCl binding. Triticum aestivum plants under 200 mM NaCl stress with different combinations of treatments showed that bacterial consortium provides tolerance. Under 200 mM salt stress the shoot length was 7.74 cm and total chlorophyll was 4.16 mg g-1Fw of the uninoculated plants whereas inoculated ones were 9.94 cm and 5.62 mg g-1Fw respectively. Under salinity stress, membrane stability index was increased from 47 % to 61 % and electrolyte leakage was decreased to 48 % from 64 %, after inoculation with bacterial consortium. Therefore, consortium comprising of these halotolerant and biofilm forming, EPS producing bioinoculants provides salt tolerance and can be exploited as a sustainable alternative for stress tolerance.

Efficacy of Bacillus Calmette-Guérin in Cancer Prevention and Its Putative Mechanisms.

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.

Silent epidemic of silicotuberculosis in India and emergence of multidrug-resistant tuberculosis?

India's projected silica-dust-exposed workers will be 52 million at the end of 2025. Elimination of tuberculosis is also targeted in India by 2025. Scientists in India have already pointed out that unless silicosis is controlled, the said elimination is difficult to achieve. This study evidences an increasing incidence of tuberculosis and multidrug resistant tuberculosis (MDR-TB) with five deaths due to treatment failure among the silica dust-exposed workers compared to their unexposed counterparts. It was also observed that both tuberculosis as well as MDR-TB were directly proportional to the dose and/or duration of silica dust exposure. This means the incidence of MDR-TB is lowest in the unexposed group, moderate in the radiologically negative but silica dust exposed group (subradiological silicosis due to moderate exposure), and highest in the radiologically confirmed silicotic workers (maximally exposed group. Since India has a huge burden of silicosis, they are vulnerable to tuberculosis including multidrug-resistant tuberculosis resulting in the emergence of MDR-TB among the silica dust-exposed workers. This will also lead to a silent epidemic of silicotuberculosis in India shortly. Therefore, it would be important to have tools to quickly detect silicosis cases at an early stage to identify a vulnerable population and adopt an effective intervention measure.

Patent landscaping and citation network analysis to reveal the global research trends in biopriming using microbial inoculants: an insight toward sustainable agriculture.

As an alternative to harmful chemical fertilizers and toward fulfilling Sustainable Development Goals (SDGs) of the United Nations, growth promoting rhizobacterial bioinoculants, emerged as potential players. These act in multifunctional ways, including seed colonization, seed germination, stress tolerance and many more, leading to proper growth and development of plants. Biopriming seeds with these beneficial multi-trait microbes is an effective way to introduce them in the soil, and this is an example of bottom-up approach of rhizosphere engineering. Using such sustainable approach is promising and, to investigate and analyze, their research trends are of prime importance. Thus, data were retrieved using Lens and Scopus databases and used for patent landscaping and citation network analysis, respectively. For patent landscaping, documents obtained using customized keyword search were broadly from the past 35 years (1987-2022) and yielded 114 patents which were manually curated in title, abstract and claims (TAC). From the year 2000, interest in this area was observed which further gained momentum from the year 2008, and a maximum peak was observed in the year 2021. Patent profile (filed, granted and published) showed an upward trend during this tenure (1987-2022). In this research article, we aim to provide an overview of current research in this field, identify research hotspots, project future development prospects and make recommendations for further research. Patent landscaping and citation network analysis were used to analyze the recent trends in biopriming approaches using microbial bioinoculants for the first time to identify progress and hotspots in the field of seed priming with PGPRs.

TLR4 activation by lysozyme induces pain without inflammation.

Mostly, pain has been studied in association with inflammation, until recent studies which indicate that during bacterial infections, pain mechanisms could be independent of the inflammation. Chronic pain can sustain long after the healing from the injury, even in the absence of any visible inflammation. However, the mechanism behind this is not known. We tested inflammation in lysozyme-injected mice foot paw. Interestingly, we observed no inflammation in mice foot paw. Yet, lysozyme injections induced pain in these mice. Lysozyme induces pain in a TLR4-dependent manner and TLR4 activation by its ligands such as LPS leads to inflammatory response. We compared the intracellular signaling of MyD88 and TRIF pathways upon TLR4 activation by lysozyme and LPS to understand the underlying mechanism behind the absence of an inflammatory response upon lysozyme treatment. We observed a TLR4 induced selective TRIF and not MyD88 pathway activation upon lysozyme treatment. This is unlike any other previously known endogenous TLR4 activators. A selective activation of TRIF pathway by lysozyme induces weak inflammatory cytokine response devoid of inflammation. However, lysozyme activates glutamate oxaloacetate transaminase-2 (GOT2) in neurons in a TRIF-dependent manner, resulting in enhanced glutamate response. We propose that this enhanced glutaminergic response could lead to neuronal activation resulting in pain sensation upon lysozyme injections. Collectively we identify that TLR4 activation by lysozyme can induce pain in absence of a significant inflammation. Also, unlike other known TLR4 endogenous activators, lysozyme does not activate MyD88 signaling. These findings uncover a mechanism of selective activation of TRIF pathway by TLR4. This selective TRIF activation induces pain with negligible inflammation, constituting a chronic pain homeostatic mechanism.

An isolated subcutaneous paraspinal pseudo-tumor-more to it than meets the eye-a case report and review of literature.

A 4-year-old male child presented to us with a paraspinal pseudo-tumor over the mid-back region with pain being his only symptom. On initial ultrasonography, it was presumed to be a nerve sheath tumor, but on an excision biopsy and histopathology, it proved to be a subcutaneous cysticercosis. Furthermore, an MRI of the brain showed a ring enhancing lesion with vasogenic edema, which confirmed the diagnosis of a neurologically symptomless neurocysticercosis. We treated the patient with albendazole and a short course of dexamethasone. There was complete resolution of the painful subcutaneous swelling, and the patient remained neurologically symptomless at all subsequent follow-ups. Resolution of the brain lesions was seen in the 6-month MRI follow-up. Although rare, orthopedic surgeons should consider the possibility of parasitic infections when dealing with small near-asymptomatic soft tissue paraspinal swellings of uncertain etiology. A thorough investigation in such cases can be lifesaving.

Automatic diagnosis of COVID-19 with MCA-inspired TQWT-based classification of chest X-ray images.

In this era of Coronavirus disease 2019 (COVID-19), an accurate method of diagnosis with less diagnosis time and cost can effectively help in controlling the disease spread with the new variants taking birth from time to time. In order to achieve this, a two-dimensional (2D) tunable Q-wavelet transform (TQWT) based on a memristive crossbar array (MCA) is introduced in this work for the decomposition of chest X-ray images of two different datasets. TQWT has resulted in promising values of peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) at the optimum values of its parameters namely quality factor (Q) of 4, and oversampling rate (r) of 3 and at a decomposition level (J) of 2. The MCA-based model is used to process decomposed images for further classification with efficient storage. These images have been further used for the classification of COVID-19 and non-COVID-19 images using ResNet50 and AlexNet convolutional neural network (CNN) models. The average accuracy values achieved for the processed chest X-ray images classification in the small and large datasets are 98.82% and 94.64%, respectively which are higher than the reported conventional methods based on different models of deep learning techniques. The average accuracy of detection of COVID-19 via the proposed method of image classification has also been achieved with less complexity, energy, power, and area consumption along with lower cost estimation as compared to CMOS-based technology.