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Background: The study was planned to assess the use of low shrinkage composites for restoring cavities with high configuration factor (C-factor) which are subjected to high stresses. Aim: The aim of the study was to evaluate the effect of C- factor on tensile bond strength to human dentin using methacrylate based nanohybrid and low shrinkage silorane composite. Materials and Methods: In this study 40 non carious human molar teeth were selected and assigned into two main groups - cavity (Class I cavity with high C-factor) and flat group (flat surface with low C-factor). Two different composite materialsmethacrylate based and silorane low shrinkage composite were used to restore the teeth. Dentin surface was treated, adhesive application was done and composite was applied as per manufacturer’s instructions. Samples were stored in distilled water then subjected to tensile bond strength measurement using universal testing machine. Results: Statistical analysis was done using Independent sample t-test. The mean bond strength in methacrylate based and silorane composite was significantly higher in flat preparation (Low C-factor) than cavity preparation. The mean bond strength in both cavity (High C-factor) and flat preparation(Low C-factor) was significantly higher in silorane than in conventional methacrylate based composite. Conclusion: The bond strength of composites to dentin is strongly influenced by C-factor and type of composite resin material used.

Rationale: Early mortality in intracerebral hemorrhage (ICH) is due to hematoma volume (HV) expansion, and there are no effective treatments available other than reduction in blood pressure. Tranexamic acid (TXA) a hemostatic drug that is widely available and safe can be a cost-effective treatment for ICH, if proven efficacious., Hypothesis: Administration of TXA in ICH patients when given within 4.5 h of symptom onset will reduce early mortality at 30 days., Design: Indian Trial of Tranexamic acid in Spontaneous Intracerebral Haemorrhage (INTRINSIC trial) is a multicenter, randomized, open-label, trial enrolling patients aged more than 18 years presenting with non-traumatic ICH within 4.5 h of symptom onset or when last seen well. Study participants received 2 g of TXA administered within 45 min while control group received standard of care. Intensive blood pressure reduction as per INTERACT 2 protocol is followed is done in both groups. Study plans to recruit 3400 patients. Primary outcome is mortality at day 30. Secondary outcomes are radiological reduction in HV at 24 h from baseline, neurological impairment at day 7 or earlier (if discharged), and assessments of dependency and quality of life at day 90., Summary: If proven to be beneficial, TXA will have a major impact on medical management of ICH., Trial Registration: Clinical Trial Registry India (CTRI/2023/03/050224) and Clinical Trials.gov (NCT05836831)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Osteoarthritis (OA) is a prevalen degenerative joint disease with no FDA-approved therapies that can halt or reverse its progression. Current treatments address symptoms like pain and inflammation, but not underlying disease mechanisms. OA progression is marked by increased inflammation and extracellular matrix (ECM) degradation of the joint cartilage. While the role of biochemical cues has been widely studied for OA, how matrix mechanical cues influence OA phenotype remains poorly understood. Using sliding hydrogels (SGs) as a tool, we examine how local matrix compliance in 3D modulates OA chondrocyte phenotype and associated mechanosensing. We demonstrate that local matrix compliance reduces the inflammatory phenotype of OA chondrocytes, as indicated by decreased gene expression of catabolic markers and proinflammatory cytokine secretion. This is achieved via significantly reduced nuclear NF-κB expression and signaling in OA chondrocytes. Live cell imaging shows enhanced cellular and nuclear dynamics with increased matrix deformation in the compliant SG. Blocking cellular dynamics negates SG compliance-induced benefits in reducing OA inflammatory phenotype. Further, SG alters nuclear mechanosensing in OA as indicated by increased nuclear lamin reinforcement and chromatin condensation. Finally, we demonstrate that a drug inhibiting histone lysine demethylase to modulate chromatin accessibility reduces OA inflammation in 3D hydrogels. These findings advance our understanding of how ECM mechanics regulate OA mechanobiology and progression and highlight potential disease-modifying treatments via epigenetic and mechanosensing-based therapies., (© 2024 Wiley Periodicals LLC.)

Developing a two-dimensional (2D) ultrathin metal-organic framework plays a significant role in energy conversion and storage systems. This work introduced a facile strategy for engineering ultrathin NiMn-MOF nanosheets on Ni foam (NF) via in situ conversion from NiMn-layered double hydroxide (LDH). The as-synthesized LDH-derived NiMn-MOF (LDH-D NiMn-MOF) nanosheet exhibited an overpotential of 350 mV to drive a current density of 100 mA cm -2 during oxygen evolution reaction (OER) owing to its better redox activity, hierarchical architecture, and intercalating ability. The similar effective catalytic trend was noticed during the urea-assisted water oxidation process. The developed catalyst required only a potential of 1.39 V vs. RHE at 100 mA cm -2 towards urea oxidation reaction (UOR). Moreover, the urea-assisted overall water-splitting voltage was found to be 1.5 V at the current density of 10 mA cm -2 . Furthermore, the same catalyst was explored as an energy-storage material for supercapattery application with an aerial specific capacity value of 2613.9 mC cm -2 at 1 mA cm -2 which was found to be 1.5 times higher than NiMn-LDH (1724.3 mC cm -2 ). Additionally, an aqueous asymmetric supercapattery device was fabricated which demonstrated the best electrochemical performance and provided a maximum energy density of 64.1 Wh kg -1 at a power density of 493 W kg -1 with 77.8 percent capacity retention after a continuous run of 8000 cycles at 10 mA cm -2 current density. Hence, the multifaceted properties of energy conversion and storage of LDH-D NiMn-MOF outline its performance in real-world applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery., (© 2024. The Author(s).)

Post-implantation, the pluripotent epiblast in a human embryo forms a central lumen, paving the way for gastrulation. Osmotic pressure gradients are considered the drivers of lumen expansion across development, but their role in human epiblasts is unknown. Here, we study lumenogenesis in a pluripotent-stem-cell-based epiblast model using engineered hydrogels. We find that leaky junctions prevent osmotic pressure gradients in early epiblasts and, instead, forces from apical actin polymerization drive lumen expansion. Once the lumen reaches a radius of ∼12 μm, tight junctions mature, and osmotic pressure gradients develop to drive further growth. Computational modeling indicates that apical actin polymerization into a stiff network mediates initial lumen expansion and predicts a transition to pressure-driven growth in larger epiblasts to avoid buckling. Human epiblasts show transcriptional signatures consistent with these mechanisms. Thus, actin polymerization drives lumen expansion in the human epiblast and may serve as a general mechanism of early lumenogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade., Methods: In this study, we have tested the function of the cartilage-resident IL1R1 + TNF-R2 + Inf-A cells in OA. We have identified that the IL1R1 + TNF-R2 + Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice., Results: Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants., Conclusion: These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling., (© 2024. The Author(s).)

Objective: Adult skeletal stem cells (SSCs) that give rise to chondrocytes, osteocytes, and stromal cells as progeny have been shown to contribute to cartilage regeneration in osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase Tet1 regulates SSC function in OA., Methods: We investigated the differences in the SSC lineage tree and differentiation potential in neonatal and adult Tet1 +/+ and Tet1 -/- mice with and without injury and upon OA induction and progression. Using RNA sequencing, the transcriptomic differences between SSCs and bone cartilage stroma progenitor cells (BCSPs) were identified in Tet1 +/+ mice and Tet1 -/- mice., Results: Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSCs and BCSPs. Tet1 inhibition led to enhanced chondrogenesis in human SSCs and chondroprogenitors isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of OA led to increased cartilage regeneration. Transcriptomic analyses of SSCs and BCSPs lacking Tet1 revealed pathway alterations in transforming growth factor β signaling, melatonin degradation, and cartilage development-associated genes. Lastly, we report that use of the hormone melatonin can dampen inflammation and improve cartilage health., Conclusion: Although Tet1 is a broad epigenetic regulator, melatonin can mimic the inhibition ability of TET1 to enhance the chondrogenic ability of SSCs. Melatonin administration has the potential to be an attractive stem cell-based therapy for cartilage regeneration., (© 2023 American College of Rheumatology.)

Root biomodifiers help in removing the smear layer following mechanical debridement. In this context, we evaluated and compared the in vitro efficacy of MTAD, MTAD+I-PRF, and phosphate-buffered saline-conditioned dentin surfaces by examining the distribution of the fibrin network using scanning electron microscopy. It was concluded that MTAD can serve as a potentially useful root conditioner/biomodifier. Further, the adjunct of MTAD+I-P resulted in more fibrin network linkage on the dentinal surface when compared to MTAD alone which can be of great utility in Advanced Regenerative Therapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Advances in the profiling of human joint tissues at single-cell resolution have provided unique insights into the organization and function of these tissues in health and disease. Data generated by various single-cell technologies, including single-cell RNA sequencing and cytometry by time-of-flight, have identified the distinct subpopulations that constitute these tissues. These timely studies have provided the building blocks for the construction of single-cell atlases of joint tissues including cartilage, bone and synovium, leading to the identification of developmental trajectories, deciphering of crosstalk between cells and discovery of rare populations such as stem and progenitor cells. In addition, these studies have revealed unique pathogenetic populations that are potential therapeutic targets. The use of these approaches in synovial tissues has helped to identify how distinct cell subpopulations can orchestrate disease initiation and progression and be responsible for distinct pathological outcomes. Additionally, repair of tissues such as cartilage and meniscus remains an unmet medical need, and single-cell methodologies can be invaluable in providing a blueprint for both effective tissue-engineering strategies and therapeutic interventions for chronic joint diseases such as osteoarthritis and rheumatoid arthritis., (© 2023. Springer Nature Limited.)

Biofilm-producing Pseudomonas aeruginosa infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat P. aeruginosa infections. Ten MDR/XDR P. aeruginosa strains and five P . aeruginosa -specific phages were genetically characterized and evaluated based upon their antibiotic susceptibilities and phage sensitivities. Two selected strains, AR351 (XDR) and I0003-1 (MDR), were treated singly and in combination with either a broad-spectrum or narrow-spectrum phage, phage EM-T3762627-2_AH (EM), or 14207, respectively, and bactericidal antibiotics of five classes in biofilm time-kill analyses. Synergy and/or bactericidal activity was demonstrated with all PACs against one or both drug-resistant P. aeruginosa strains (average reduction: -Δ3.32 log 10 CFU/cm 2 ). Slightly improved ciprofloxacin susceptibility was observed in both strains after exposure to phages (EM and 14207) in combination with ciprofloxacin and colistin. Based on phage cocktail optimization with four phages (EM, 14207, E20050-C (EC), and 109), we identified several effective phage-antibiotic cocktails for further analysis in a 4-day pharmacokinetic/pharmacodynamic in vitro biofilm model. Three-phage cocktail, EM + EC + 109, in combination with ciprofloxacin demonstrated the greatest biofilm reduction against AR351 (-Δ4.70 log 10 CFU/cm 2 from baseline). Of remarkable interest, the addition of phage 109 prevented phage resistance development to EM and EC in the biofilm model. PACs can demonstrate synergy and offer enhanced eradication of biofilm against drug-resistant P. aeruginosa while preventing the emergence of resistance., Competing Interests: M.J.R. received research support, consulted or participated in a speaker bureau for AbbVie, Basilea, Entasis, La Jolla, Merck, Paratek, Shionogi, and T2 Biosystems, and was partially funded by NIAID R21AI163726.

Introduction and Importance: Langerhans cell histiocytosis (LCH) is a proliferation of dendritic mononuclear cells with infiltration into organs locally or diffusely. Its aetiology is still unknown, and its clinical spectrum is quite wide., Case Presentation: A 2-year-old-male child presented to us with a solitary swelling in left mandibular region which was painless and increasing in size with time. It was diagnosed to be unifocal LCH of mandible on the basis of X-ray, ultrasonography of the involved mandible and fine needle aspiration cytology of the swelling and managed conservatively with oral steroids., Discussion: LCH is often classified as single system, when the disease affects only one part of the body; or multisystem, when it affects more than one part of the body (Jezierska et al., 2018 [1]). In children, histiocytosis usually involves the bones and may consist of single or multiple sites. The skull is frequently affected. Children over five years of age usually have the single system disease, with just bone involvement but our patient was 2-year-old and had unifocal disease involving mandible. Young children, especially infants, are more likely to have the multisystem disease (Jezierska et al., 2018 [1])., Conclusion: Mandibular involvement associated with LCH is quite uncommon in paediatric population. Early diagnosis and prompt initiation of treatment are key to a good eventual outcome., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: A border zone infarct (BI) is defined as an infarction that is localized to watersheds or border zones in the brain. BI is further classified into cortical border zone infarct (CBZ) and internal border zone infarct (IBZ). This study was conducted to explore the clinical and radiological characteristics of BI., Materials and Method: The study was conducted on eligible 400 acute ischemic stroke patients out of which 52 BI patients (diagnosed by the radiologist on DWI MRI images), patients >18 yrs of age were selected and divided into two groups of IBZ and CBZ infarct patients. The degree of intracranial and extracranial stenosis and characteristics on clinical presentation were assessed. The data were collected and analyzed using SPSS version 20.0 software at significance level p-value <0.05., Results: 25% and 75% of CBZ and IBZ patients, respectively, had history of presyncope or syncope before stroke. On vascular evaluation, 3.9% and 51.9% were in MCA and ICA stenosis group, respectively. Evidence of cardio embolism was found in 17.3% of patients. 53.3% of CBZ and 53.8% of IBZ patients were in ICA stenosis group, and 6.7% of CBZ and 7.7% of IBZ patients were in MCA stenosis group, with a statistically insignificant relation (p-value >0.05)., Conclusion: Association of BI with events causing hypotension or hypovolemia is well-established in our study, association of BI with large vessel atherosclerosis is common, and its contribution to CBZ and IBZ seems to be equal., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset-560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r = 0.30, p < 0.0001), and two brain regions (the left inferior parietal and left suparmarginal) with top predictive connections were identified as disease epicenters of ASD. Our study highlights a critical role of network architecture in a continuum model of ASD spanning from healthy individuals with genetic risk to individuals with ASD. Our study also highlights the strength of investigating polygenic risk scores in addition to multi-modal neuroimaging measures to better understand the interplay between genetic risk and brain alterations associated with ASD., (© 2022. The Author(s).)

No disease-modifying drug exists for osteoarthritis (OA). Despite success in animal models, candidate drugs continue to fail in clinical trials owing to the unmapped interpatient heterogeneity and disease complexity. We used a single-cell platform based on cytometry by time-of-flight (cyTOF) to precisely outline the effects of candidate drugs on human OA chondrocytes. OA chondrocytes harvested from patients undergoing total knee arthroplasty were treated with 2 drugs, an NF-κB pathway inhibitor, BMS-345541, and a chondroinductive small molecule, kartogenin, that showed preclinical success in animal models for OA. cyTOF conducted with 30 metal isotope-labeled antibodies parsed the effects of the drugs on inflammatory, senescent, and chondroprogenitor cell populations. The NF-κB pathway inhibition decreased the expression of p-NF-κB, HIF2A, and inducible NOS in multiple chondrocyte clusters and significantly depleted 4 p16ink4a-expressing senescent populations, including NOTCH1+STRO1+ chondroprogenitor cells. While kartogenin also affected select p16ink4a-expressing senescent clusters, there was a less discernible effect on chondroprogenitor cell populations. Overall, BMS-345541 elicited a uniform drug response in all patients, while only a few responded to kartogenin. These studies demonstrate that a single-cell cyTOF-based drug screening platform can provide insights into patient response assessment and patient stratification.

Objectives: Coronavirus disease 2019 (COVID-19) has neurologic manifestations associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to retrospectively analyze SARS COVID-19 patients with neurological manifestations and identify patterns of presentation including the site of neuroaxis involvement, neuroimaging, and associated systemic involvement., Methods and Subjects: This retrospective observational study was conducted at two tertiary care hospitals in western Rajasthan. Data on age, sex, presenting symptoms, and comorbidities (hypertension, diabetes, cardiac, cerebrovascular disease, and cancer) were collected from 28th February 2020 to 31st December 2020 through medical records, discharge summaries, and radiological studies. Verbal/written patient consent was obtained due to the prevailing COVID-19 norms at the time of the first wave. Major inclusion criteria were as follows: age &gt;18 years, consent from patient/surrogate, positive RT-PCR report in case of active COVID cases, or positive COVID antibody test in case of post-COVID neurological sequelae. All neurological manifestations were reviewed by at least two neurologists and were divided into central nervous system (CNS) and peripheral nervous system (PNS) manifestations. Systemic features and their temporal relationship with neurological features were recorded. Various other specialized assessments and therapeutic interventions were conducted. Statistical analysis was performed using the SPSS software. A Chi-square test was performed to determine the association between variables. Student's t-test and one-way analysis of variance were used to determine differences in mean values. Statistical significance was set at p &lt; 0.05., Results: The mean age was 57.32 years for the CNS group and 40 years for the PNS group (p = 0.025). Age was significantly lower in the PNS group than in the CNS group (p = 0.025). Anemia, leucocytosis, and elevated serum creatinine were more commonly seen in the CNS group, although the difference was not statistically significant. The most common CNS manifestations were stroke (41.8%), of which ischemic stroke constituted 83% of cases, followed by seizure (22%), encephalopathy (20.9%), headache (15.1%), and vertigo (3.8%). The most common PNS manifestation was neuropathy (57%), which included Guillain-Barré syndrome (GBS), critical illness neuropathy, and autonomic neuropathy Conclusion: CNS symptoms of COVID-19 are more common than PNS symptoms. Stroke is the most frequent (46%) COVID-CNS symptom, which occurs in people of age above 35 years and is associated with high mortality., (© Journal of the Association of Physicians of India 2011.)

Background: Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ)., Methods: We assessed PRS-SCZ and cortical morphometry in typically developing children and adolescents (3-21 years, 46.8% female) using whole-genome genotyping and T1-weighted magnetic resonance imaging ( n  = 390) from the PING (Pediatric Imaging, Neurocognition, and Genetics) cohort. We contextualized the findings using 1) age-matched transcriptomics, 2) histologically defined cytoarchitectural types and functionally defined networks, and 3) case-control differences of schizophrenia and other major psychiatric disorders derived from meta-analytic data of 6 ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) working groups, including a total of 12,876 patients and 15,670 control participants., Results: Higher PRS-SCZ was associated with greater cortical thickness, which was most prominent in areas with heightened gene expression of dendrites and synapses. PRS-SCZ-related increases in vertexwise cortical thickness were mainly distributed in association cortical areas, particularly the ventral attention network, while relatively sparing koniocortical type cortex (i.e., primary sensory areas). The large-scale pattern of cortical thickness increases related to PRS-SCZ mirrored the pattern of cortical thinning in schizophrenia and mood-related psychiatric disorders derived from the ENIGMA consortium. Age group models illustrate a possible trajectory from PRS-SCZ-associated cortical thickness increases in early childhood toward thinning in late adolescence, with the latter resembling the adult brain phenotype of schizophrenia., Conclusions: Collectively, combining imaging genetics with multiscale mapping, our work provides novel insight into how genetic risk for schizophrenia affects the cortex early in life., (© 2022 The Authors.)

Background: Endophytic bacteria overlay significant role in plant growth promotion, eliminating phyto-pathogens and combating stress-conditions. In the present study, we aimed to screen high salt tolerant bacteria and study their adaptive response to elevated salt concentrations. A total of 46 endophytic bacterial isolates from Vigna radiata were screened for salt tolerance. The high salt tolerant endophytic isolate was characterized for alteration in morphology, growth rate, protein profiling, and compatible solute concentrations., Results: The isolate MHN12, based upon biochemical characterization and partial 16S rDNA sequencing identified as B. licheniformis (accession number MG273753) was able to tolerate up to 15% NaCl (Sodium Chloride) (2.6 M) concentration. The isolate possessed 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity along with indole acetic acid (IAA), siderophore, ammonia, organic acid and hydrogen cyanide (HCN) production. Accumulation of proline was apparent up to 7.5% NaCl concentration and declined afterwards. Ultrastructure analysis using TEM (transmission electron microscopy) revealed the morphological alteration from rods to filaments., Conclusion: Acclimatization to salt stress and plant growth promoting activities could contribute to utilization of this bacterium as bioinoculant to enhance the crop yield and discourage the application of chemical fertilizers., (© 2022. The Author(s).)

•PIH is a leading cause of maternal and perinatal morbidity and mortality worldwide.•Hypercoagulability is constantly associated with hypertensive disorders of pregnancy and particularly associated with pre-eclampsia.•The aims and objectives of this study were to compare the platelet parameters and coagulation profile in normotensive pregnant females along with gestational hypertension cases and pre-eclamptia patients., Competing Interests: NIL., (© 2022 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Introduction: Ovarian teratomas are most common germ cell neoplasms. Immature ovarian teratoma comprises less than 1% of all ovarian teratomas. It usually occurs in first two decades of life., Case Presentation: We report a case of 4 years old female child presenting with pain and huge lump in lower abdomen. On abdominal ultrasonography, it revealed a solid-cystic pelvic lesion arising from left ovary. Magnetic resonance imaging (MRI) corroborated the ultrasonographic findings. She underwent laparotomy with right oophorectomy with excision of the mass. The histopathological examination of the excised mass confirmed it to be immature ovarian teratoma with yolk sac tumor. The patient had an uneventful recovery with no sign of tumor recurrence at a one and a half year follow-up., Conclusion: In spite of immature ovarian teratomas having aggressive behaviour and lethal outcome, a high degree of suspicion and timely management can translate into a very good eventual prognosis., Competing Interests: The authors declare that they have no competing interest., (© 2022 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

In the present study, nonrhizobial endophytes were isolated from Pisum sativum and Cicer arietinum from Haryana, India. A total of 355 bacterial endophytes were screened for plant growth promoting traits. Out of all, 96 bacterial endophytes were selected based on morphological characters and multi-PGP traits, and their diversity analyzed by amplified ribosomal DNA restriction analysis. Based on their ARDRA profile, the 25 representative isolates (12 from P. sativum and 13 from C. arietinum), were selected and identified by 16S ribosomal DNA sequencing. Genetic relatedness based on BLAST analysis revealed the similarity of these isolates with members of three prominent phyla, that is, Proteobacteria, Firmicutes, and Actinobacteria. The dominant cluster, Firmicutes, constituted 60% of the isolates, assigned to four different genera, Bacillus, Staphylococcus, Ornithinibacillus, and Lysinibacillus. Phylum α-proteobacteria included two genera, namely Paenochrobactrum and Ochrobactrum and three genera in phylum γ-proteobacteria, namely Pseudomonas, Pantoea and Proteus. The phylum Actinobacteria was constituted of two genera, Microbacterium and Arthrobacter. Bacillus zhangzhouensis, Bacillus safensis, Arthrobacter enclensis from P. sativum and Bacillus haynesii, Paenochrobactrum sp. from C. arietinum are documented as plant growth promoting endophytic bacteria for the first time in the present study. The in vitro and in vivo assessment based on bonitur score revealed that the endophytic isolates Bacillus mojavensis PRN2, Pseudomonas chlororaphis PHN9, B. safensis PRER2, Pseudomonas sp. RCP1, Pseudomonas lini PRN1 and B. haynensii RCP3 from P. sativum and C. arietinum significantly enhanced the plant growth parameters. Therefore, these potential isolates can be further harnessed for preparation of bioformulations to enhance sustainable agriculture., (© 2022 Wiley-VCH GmbH.)

Mesenchymal stromal cells (MSCs) have been widely investigated for their regenerative capacity, anti-inflammatory properties and beneficial immunomodulatory effects across multiple clinical indications. Nevertheless, their widespread clinical utilization is limited by the variability in MSC quality, impacted by donor age, metabolism, and disease. Human induced pluripotent stem cells (hiPSCs) generated from readily accessible donor tissues, are a promising source of stable and rejuvenated MSC but differentiation methods generally require prolonged culture and result in low frequencies of stable MSCs. To overcome this limitation, we have optimized a quick and efficient method for hiPSC differentiation into footprint-free MSCs (human induced MSCs [hiMSCs]) in this study. This method capitalizes on the synergistic action of growth factors Wnt3a and Activin A with bone morphogenetic protein-4 (BMP4), leading to an enrichment of MSC after only 4 days of treatment. These hiMSCs demonstrate a significant upregulation of mesenchymal stromal markers (CD105 + , CD90 + , CD73, and cadherin 11) compared with bone marrow-derived MSCs (bmMSCs), with reduced expression of the pluripotency genes (octamer-binding transcription factor [ Oct-4 ], cellular myelocytomatosis oncogene [ c-Myc ] , Klf4, and Nanog homebox [Nanog ]) compared with hiPSC. Moreover, they show improved proliferation capacity in culture without inducing any teratoma formation in vivo . Osteogenesis, chondrogenesis, and adipogenesis assays confirmed the ability of hiMSCs to differentiate into the three different lineages. Secretome analyses showed cytokine profiles compared with bmMSCs. Encapsulated hiMSCs in alginate beads cocultured with osteoarthritic (OA) cartilage explants showed robust immunomodulation, with stimulation of cell growth and proteoglycan production in OA cartilage. Our quick and efficient protocol for derivation of hiMSC from hiPSC, and their encapsulation in microbeads, therefore, presents a reliable and reproducible method to boost the clinical applications of MSCs.

Introduction: A timely diagnosis is critical for management of Neonatal sepsis. Blood Culture is considered to be the "Gold Standard" for its diagnosis, but it has some limitations. In recent times, highly sensitive and specific inflammatory markers like interleukins, ELISA, counter immune-electrophoresis etc. have been in use for its diagnosis. But these are impractical for developing countries, due to their high cost and requirement of sophisticated equipments. A combination of haematological parameters like total leucocyte count (TLC), immature to total neutrophil ratio (I/T ratio), absolute neutrophil count (ANC), platelet count and C-reactive protein (CRP) estimation provide an early diagnosis of bacteremia. This study was undertaken to evaluate the usefulness of the above mentioned parameters as indicators for early diagnosis of neonatal sepsis., Material and Methods: In the present cross-sectional study, we intent to analyse various hematologic parameters in 160 neonates admitted in the neonatal care unit of a tertiary care hospital in Delhi. We obtained data from the records of blood culture and complete blood counts of neonates from pathology and microbiology departments of the hospital. Out of 160 admitted neonates, 80 were taken as cases and remaining 80 were taken as controls. Medical records were studied to identify infants born at ≥ 34 weeks gestation. CBCs was analysed, blood cultures and CRP were done in department of Microbiology. CBC, CRP and Blood culture was done as per standard protocols and clinical assesment by paediatrician. The statistical analyses were performed using SPSS version 22 for windows., Results: Among 80 neonates, who were in early neonatal sepsis, 44 cases (55%) were females, and 36 (45%) were males. The Microbiological profile of 80 septic neonates was analysed. The I/T value, ANC and CRP values were significantly higher in the neonates suffering from sepsis as compared to the control group. Among 80 septic neonates (cases), 30 (37.5%) were having normal ANC while 50 (62.5%) were having increased ANC and 34 (42.5%) were having normal I:T ratio while 46 (57.5%) were having increased I:T ratio. Out of 80 septic neonates (cases), 18 (22.5%) were having normal CRP while 62 (77.5%) were having increased CRP., Conclusion: ANC, I/T Ratio and CRP are quick, simple and cost-effective routine laboratory tests which help in early diagnosis of neonatal sepsis. Although there are many serological markers available, ANC and I/T Ratio serves as a reliable predictor of neonatal sepsis. With a good sensitivity, high specificity and a good negative predictive value these parameters can therefore help in timely and early identification of neonatal sepsis., Competing Interests: NIL., (© 2022 The Authors.)

•PXE is an extremely rare autosomal recessive disease.•It involves major systems in the body like the cutaneous, ocular, cardiovascular, and gastrointestinal.•The characteristic histopathological features are calcification and fragmentation of the elastic fibres.•Currently, specific or effective treatment is not available., Competing Interests: We don't have any conflict of interest., (© 2022 The Authors.)

Aim: The red complex includes Porphyromonas gingivalis , Treponema denticola , and Tannerella forsythia , which are recognized as the most important pathogens and are the indicators of infection in chronic periodontal disease. This study was to assess the levels of red complex bacteria in chronic periodontitis patients following treatment with probiotic mouthwash., Materials and Methods: Twenty chronic periodontitis patients with ages ranging from 18 to 55 years were recruited for the study. The control group was given placebo mouthwash and the study group was given probiotic mouthwash. After clinical monitoring and scaling and root planing, the collected plaque samples at baseline and 14th day were transferred for microbiological analysis by transport media for Conventional Multiplex Polymerase Chain Reaction., Results: On the 14th day, all the clinical parameters were significantly reduced in the study group with gingival index ( p = 0.003 HS) and plaque index ( p = 0.001 VHS). In the study group, there was significant bacterial cell reduction with T. denticola ( p = 0.041 S) and T. forsythia ( p = 0.037 S)., Conclusion: In patients with chronic periodontitis, treatment with probiotic mouthwash significantly reduces the levels of red complex bacteria., Clinical Significance: The use of probiotic mouthwash could be a useful adjunct to scaling and root planing in chronic periodontitis.

Background: Molecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear., Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells., Results: In this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4 + and CD8 + T cells in the TME. In addition, CD163 + tumor associated-macrophages were positively associated with S100A7 and cPLA2 expression in malignant breast cancer patients., Conclusions: Our study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer., (© 2022. The Author(s).)

Changes in the composition and viscoelasticity of the extracellular matrix in load-bearing cartilage influence the proliferation and phenotypes of chondrocytes, and are associated with osteoarthritis. However, the underlying molecular mechanism is unknown. Here we show that the viscoelasticity of alginate hydrogels regulates cellular volume in healthy human chondrocytes (with faster stress relaxation allowing cell expansion and slower stress relaxation restricting it) but not in osteoarthritic chondrocytes. Cellular volume regulation in healthy chondrocytes was associated with changes in anabolic gene expression, in the secretion of multiple pro-inflammatory cytokines, and in the modulation of intracellular calcium regulated by the ion-channel protein transient receptor potential cation channel subfamily V member 4 (TRPV4), which controls the phosphorylation of glycogen synthase kinase 3β (GSK3β), an enzyme with pleiotropic effects in osteoarthritis. A dysfunctional TRPV4-GSK3β pathway in osteoarthritic chondrocytes rendered the cells unable to respond to environmental changes in viscoelasticity. Our findings suggest strategies for restoring chondrocyte homeostasis in osteoarthritis., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Pneumonia is the most common cause of death in children under five years of age. Epidemiological factors and the disease burden differ in developing and industrialized countries. The present study is a cross sectional observational study, carried out from August 2018 to August 2020 in Hindu Rao Hospital, to assess the prevalence of congenital heart disease (CHD) in patients with pneumonia in children up to 5 years. The main objectives of the study were to study the prevalence of congestive cardiac failure (CCF) in pneumonia with and without congenital heart disease., Material and Methods: Patients under 5 years of age, presenting with pneumonia during August 2018 to July 2020 were enrolled for study. The bio-data of each patient was documented each patient was clinically evaluated thoroughly and findings noted. Pneumonia was diagnosed on typical history, physical findings, blood investigations and chest radiographic finding of pneumonia infiltrates in either one or both lung fields. All the cases of pneumonia underwent transthoracic 2 Dimensional (2D) and Doppler echocardiography, done by the cardiologist. Any congenital heart disease so found was noted. The type and size of the defects was documented. The ventricular septal defects were classified based on the site and size. The size of the patient ductus arteriosus was also determined. These measurements were taken to evaluate the impact of defect size on pneumonia. CCF was diagnosed when the patient fulfilled the clinical diagnostic criteria of heart failure. All the cases of pneumonia underwent transthoracic 2 Dimensional (2D) and Doppler echocardiography for diagnosis of any congenital heart disease., Results: Mean age of the children with pneumonia was 9.94 months with 77.5% of the cases below 1 year of age. Male predominance was seen with 56.3% males to 43.8% females. Prevalence of congenital heart disease among cases of pneumonia was 12.5% while that of congestive heart failure was 27.5%. Most common CHD observed was VSD (14 cases; 8.8%) followed by PDA, ASD and TGA (4; 2.5% and 3; 1.9% and 1; 0.6% cases respectively). A significant association was observed between presence of congenital heart disease and development of CCF., Conclusion: Our study demonstrates that most patients with pneumonia or recurrent pneumonia are likely to have an underlying illness at the time of pneumonia. Recurrent ALRTI often occurred in children with history of congenital heart diseases (CHD) and is also associated with Congestive Cardiac Failure. Children with CHD are more vulnerable to recurrent respiratory tract infection., Competing Interests: We do not have any conflict of interest., (© 2021 The Authors.)