Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation.

CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using a morpholino-antisense-oligonucleotide-based zebrafish model for CHARGE syndrome, we uncover a complex spectrum of abnormalities in the neural crest and the crest-derived cell types. We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment cells in a CHARGE model. We also observe defects in the specification of peripheral neurons and the craniofacial skeleton as previously reported. Chd7 morphants have impaired migration of neural crest cells and deregulation of sox10 expression from the early stages. Knocking down Sox10 in the zebrafish CHARGE model rescued the defects in Schwann cells and craniofacial cartilage. Our zebrafish CHARGE model thus reveals important regulatory roles for Chd7 at multiple points of neural crest development viz., migration, fate choice and differentiation and we suggest that sox10 deregulation is an important driver of the neural crest-derived aspects of Chd7 dependent CHARGE syndrome.

Long-Term Safety Analysis of the BBV152 Coronavirus Vaccine in Adolescents and Adults: Findings from a 1-Year Prospective Study in North India.

BACKGROUND AND OBJECTIVE: Evidence on the long-term safety of COVID-19 vaccines is scarce. Here, in continuation of our previously published results on short-term safety, we provide data on the long-term safety of the BBV152 vaccine in adolescents and adults. METHODS: This was a prospective observational study conducted from January 2022 to August 2023. Adolescents and adults receiving the BBV152 vaccine were interviewed telephonically about long-term adverse events of special interest (AESIs) after 1 year of vaccination. Risk factors of AESIs and AESIs persistent for at least 1 month were identified. RESULTS: Out of 1024 individuals enrolled, 635 adolescents and 291 adults could be contacted during the 1-year follow-up. Viral upper respiratory tract infections were reported by 304 (47.9%) adolescents and 124 (42.6%) adults in this period. New-onset skin and subcutaneous disorders (10.5%), general disorders (10.2%), and nervous system disorders (4.7%) were the common AESIs in adolescents. General disorders (8.9%), musculoskeletal disorders (5.8%), and nervous system disorders (5.5%) were the common AESIs in adults. Menstrual abnormalities were noticed in 4.6% of female participants. Ocular abnormalities and hypothyroidism were observed in 2.7% and 0.6% of participants, respectively. Among serious AESIs (1%), stroke and Guillain-Barre syndrome were identified in 0.3% and 0.1% of participants, respectively. Among adolescents, female individuals, those with a history of allergy and post-vaccination typhoid were respectively at 1.6, 2.8, and 2.8 times higher risk of AESIs. The majority of the AESIs persisted at the 1-year follow-up. Female individuals, adolescents with pre-vaccination COVID-19, those with co-morbidities, and those with post-vaccination typhoid had respectively 1.6, 2, 2.7, and 3.2 times higher odds of persistent AESIs. Adults with co-morbidities had more than 2 times higher odds of AESIs and persistent AESIs. CONCLUSIONS: The patterns of AESIs developing after BBV152 differed from those reported with other COVID-19 vaccines as well as between adolescents and adults. With the majority of AESIs persisting for a significant period, extended surveillance of COVID-19-vaccinated individuals is warranted to understand the course and outcomes of late-onset AESIs. Serious AESIs might not be uncommon and necessitate enhanced awareness and larger studies to understand the incidence of immune-mediated phenomena post-COVID-19 vaccination. The relationship of AESIs with sex, co-morbidities, pre-vaccination COVID-19, and non-COVID illnesses should be explored in future studies.

Exosomes: Mediators of cellular communication in potentially malignant oral lesions and head and neck cancers.

Exosomes are a unique type of extracellular vesicles that contain a plethora of biological cargo such as miRNA, mRNA, long non-coding RNA, DNA, proteins and lipids. Exosomes serve as very effective means of intercellular communication. Due the presence of a lipid bilayer membrane, exosomes are resistant to degradation and are highly stable. This makes them easily identifiable in blood and other bodily fluids such as saliva. The exosomes that are secreted from a parent cell directly release their contents into the cytoplasm of a recipient cell and influence their cellular activity and function. Exosomes can also transfer their content between cancer cells and normal cells and regulate the tumor microenvironment. Exosomes play a vital role in tumor growth, tumor invasion and metastasis. Exosomes provide a multitude of molecular and genetic information and have become valuable indicators of disease activity at the cellular level. This review explores the molecular characteristics of exosomes and the role that exosomes play in the tumorigenesis pathway of potentially malignant oral lesions and head and neck cancers The application of exosomes in the treatment of oral cancers is also envisioned. Exosomes are very small and can easily pass through various biological barriers, making them very good delivery vectors for therapeutic drugs as well as to selectively induce DNA's mRNA and miRNAs into targeted cancer cells.

Common tendinopathies around the elbow; what does current evidence say?

Tendinopathies are common causes of pain around the elbow resulting in significant functional impairment in athletes or the working-age population. Patients complain of a gradual onset pain with or without any specific trauma. Tissue histology shows chronic fibroblast and vascular proliferation, with a disorganized collagen pattern and absence of inflammatory mediators. Currently, numerous treatment options are described, but many of these are only supported by a heterogenous evidence base. Thus, management guidelines are difficult to define. Surgery is mostly indicated in selected cases that have failed non-operative management. This article reviews the pathophysiology and natural history of lateral and medial elbow tendinopathies, as well as distal biceps and triceps tendinopathies, and their current treatment options.

Modeling organically fertilized flooded rice systems and its long-term effects on grain yield and methane emissions.

The increasing trend of adopting organic fertilization in rice production can impact grain yields and soil methane (CH4) emissions. To simulate these impacts in the absence of long-term field data, a process-based biogeochemical model, Denitrification and Decomposition (DNDC version 9.5) was used. The model was calibrated against a single year greenhouse study and validated using a previously published one-year field trial from 1990, both comparing varying fertilization systems in rice production in southeast Texas, USA. In both the greenhouse and the field studies, lower grain yield and greater soil CH4 emissions were observed in organically fertilized systems. Calibrated model simulations of the greenhouse study correlated with the observed daily CH4 emissions (conventional r2 = 0.87; organic r2 = 0.91) and SOC (r2 = 0.83); but, the model overestimated yield of conventional systems (slope = 1.2) and underestimated yield of organic systems (slope = 0.68). For the field study, agreement between simulated and observed yields and CH4 emissions resulted in slopes close to 1. A simple organic system with urea and straw amendment from the field study was an input available in DNDC whereas the slow release, pelletized organic fertilizer used in the greenhouse study, Nature Safe, was not modeled well by DNDC. The validated model was used to simulate 22 years of rice production and predicted that the differences in yield and CH4 emissions between treatments would diminish with time. In the model simulations, the overall soil health was enhanced when managed with organic fertilization compared to conventional inorganic fertilizers. Model simulations could be improved further by including site-specific calibration of soil organic C, and soil carbon dioxide (CO2) emissions.

A Novel One-Pot Synthesis and Characterization of Silk Fibroin/α-Calcium Sulfate Hemihydrate for Bone Regeneration.

This study aims to fabricate silk fibroin/calcium sulfate (SF/CS) composites by one-pot synthesis for bone regeneration applications. The SF was harvested from degummed silkworm cocoons, dissolved in a solvent system comprising of calcium chloride:ethanol:water (1:2:8), and then mixed with a stoichiometric amount of sodium sulfate to prepare various SF/CS composites. The crystal pattern, glass transition temperature, and chemical composition of SF/CS samples were analyzed by XRD, DSC, and FTIR, respectively. These characterizations revealed the successful synthesis of pure calcium sulfate dihydrate (CSD) and calcium sulfate hemihydrate (CSH) when it was combined with SF. The thermal analysis through DSC indicated molecular-level interaction between the SF and CS. The FTIR deconvolution spectra demonstrated an increment in the ß-sheet content by increasing CS content in the composites. The investigation into the morphology of the composites using SEM revealed the formation of plate-like dihydrate in the pure CS sample, while rod-like structures of α-CSH surrounded by SF in the composites were observed. The compressive strength of the hydrated 10 and 20% SF-incorporated CSH composites portrayed more than a twofold enhancement (statistically significant) in comparison to that of the pure CS samples. Reduced compressive strength was observed upon further increasing the SF content, possibly due to SF agglomeration that restricted its uniform distribution. Therefore, the one-pot synthesized SF/CS composites demonstrated suitable chemical, thermal, and morphological properties. However, additional biological analysis of its potential use as bone substitutes is required.

An Insight into Nano Silver Fluoride-Coated Silk Fibroin Bioinspired Membrane Properties for Guided Tissue Regeneration.

The current work focuses on the development of a novel electrospun silk fibroin (SF) nonwoven mat as a GTR membrane with antibacterial, biomineralization and biocompatible properties. The γ-poly glutamic acid (γ-PGA)-capped nano silver fluoride (NSF) and silver diamine fluoride (SDF) were first synthesized, which were dip-coated onto electrospun silk fibroin mats (NSF-SF and SDF-SF). UV-Vis spectroscopy and TEM depicted the formation of silver nanoparticles. NSF-SF and SDF-SF demonstrated antibacterial properties (against Porphyromonas gingivalis) with 3.1 and 6.7 folds higher relative to SF, respectively. Post-mineralization in simulated body fluid, the NSF-SF effectively promoted apatite precipitation (Ca/P ~1.67), while the SDF-SF depicted deposition of silver nanoparticles, assessed by SEM-EDS. According to the FTIR-ATR deconvolution analysis, NSF-SF portrayed ~75% estimated hydroxyapatite crystallinity index (CI), whereas pure SF and SDF-SF demonstrated ~60%. The biocompatibility of NSF-SF was ~82% when compared to the control, while SDF-coated samples revealed in vitro cytotoxicity, further needing in vivo studies for a definite conclusion. Furthermore, the NSF-SF revealed the highest tensile strength of 0.32 N/mm and 1.76% elongation at break. Therefore, it is substantiated that the novel bioactive and antibacterial NSF-SF membranes can serve as a potential candidate, shedding light on further in-depth analysis for GTR applications.

Rehardening and the Protective Effect of Gamma-Polyglutamic Acid/Nano-Hydroxyapatite Paste on Surface-Etched Enamel.

Many revolutionary approaches are on the way pertaining to the high occurrence of tooth decay, which is an enduring challenge in the field of preventive dentistry. However, an ideal dental care material has yet to be fully developed. With this aim, this research reports a dramatic enhancement in the rehardening potential of surface-etched enamels through a plausible synergistic effect of the novel combination of γ-polyglutamic acid (γ-PGA) and nano-hydroxyapatite (nano-HAp) paste, within the limitations of the study. The percentage of recovery of the surface microhardness (SMHR%) and the surface parameters for 9 wt% γ-PGA/nano-HAp paste on acid-etched enamel were investigated with a Vickers microhardness tester and an atomic force microscope, respectively. This in vitro study demonstrates that γ-PGA/nano-HAp treatment could increase the SMHR% of etched enamel to 39.59 ± 6.69% in 30 min. To test the hypothesis of the rehardening mechanism and the preventive effect of the γ-PGA/nano-HAp paste, the surface parameters of mean peak spacing (Rsm) and mean arithmetic surface roughness (Ra) were both measured and compared to the specimens subjected to demineralization and/or remineralization. After the treatment of γ-PGA/nano-HAp on the etched surface, the reduction in Rsm from 999 ± 120 nm to 700 ± 80 nm suggests the possible mechanism of void-filling within a short treatment time of 10 min. Furthermore, ΔRa-I, the roughness change due to etching before remineralization, was 23.15 ± 3.23 nm, while ΔRa-II, the roughness change after remineralization, was 11.99 ± 3.90 nm. This statistically significant reduction in roughness change (p < 0.05) implies a protective effect against the demineralization process. The as-developed novel γ-PGA/nano-HAp paste possesses a high efficacy towards tooth microhardness rehardening, and a protective effect against acid etching.

Hydrothermal Effect on Mechanical Properties of Nephila pilipes Spidroin.

The superlative mechanical properties of spider silk and its conspicuous variations have instigated significant interest over the past few years. However, current attempts to synthetically spin spider silk fibers often yield an inferior physical performance, owing to the improper molecular interactions of silk proteins. Considering this, herein, a post-treatment process to reorganize molecular structures and improve the physical strength of spider silk is reported. The major ampullate dragline silk from Nephila pilipes with a high ß-sheet content and an adequate tensile strength was utilized as the study material, while that from Cyrtophora moluccensis was regarded as a reference. Our results indicated that the hydrothermal post-treatment (50-70 °C) of natural spider silk could effectively induce the alternation of secondary structures (random coil to ß-sheet) and increase the overall tensile strength of the silk. Such advantageous post-treatment strategy when applied to regenerated spider silk also leads to an increment in the strength by ~2.5-3.0 folds, recapitulating ~90% of the strength of native spider silk. Overall, this study provides a facile and effective post-spinning means for enhancing the molecular structures and mechanical properties of as-spun silk threads, both natural and regenerated.

Microplasma Cross-Linked Graphene Oxide-Gelatin Hydrogel for Cartilage Reconstructive Surgery.

Herein, we report the cartilage tissue engineering application of nanographene oxide (NGO)-reinforced gelatin hydrogel fabricated by utilizing a microplasma-assisted cross-linking method. NGO sheets with surface functionalities were introduced to enhance the mechanical and biomedical properties of gelatin-based hydrogels. Highly energetic reactive radicals were generated from the nonthermal plasma (NTP), which is used to facilitate the cross-linking and polymerization during the polymeric hydrogel fabrication. The NTP treatment substantially reinforced a small amount (1 wt %) of NGO into the gelatin hydrogel. Systematic material characterization thus shows that the fabricated hydrogel possessed unique properties such as moderate surface roughness and adhesiveness, suitable pores sizes, temperature-dependent viscoelasticity, and controllable degradability. In vitro studies demonstrated that the as-fabricated hydrogel exhibited excellent cell-material interactions with SW 1353 cells, bone marrow-derived mesenchymal stem cells, and a rat chondrocyte cell line, thereby exhibiting appropriate cytocompatibility for cartilage tissue engineering applications. Furthermore, an in vivo study indicated that the formation of a healthy hyaline cartilage after the microfracture was enhanced by the fabricated hydrogel implant, offering a potential biocompatible platform for microfracture-based cartilage reconstructive surgery.

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases.

INTRODUCTION: Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. AIM: Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). MATERIALS AND METHODS: The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. RESULTS: The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21-40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. CONCLUSION: The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the "Gold Standard" for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical parameters are the key for diagnosis of other forms of thyroiditis.

Antioxidant and antibacterial hydroxyapatite-based biocomposite for orthopedic applications.

Post-implantation, vicinity acquired oxidative stress and bacterial infections lead to apoptosis with eventual bone-resorption and implant failure, respectively. Thus, in order to combat aforementioned complications, present research aims in utilizing antioxidant ceria (CeO2) and antibacterial silver (Ag) reinforced hydroxyapatite (HA) composite with enhanced mechanical and cytocompatible properties. Highly dense (>90%) spark plasma sintered HA-based composites elicits enhanced elastic modulus (121-133 GPa) in comparison to that of HA. The antioxidant activity is quantified using ceria alone, wherein HA-ceria and HA-ceria-Ag pellets exhibits ~36 and 30% antioxidant activity, respectively, accrediting ceria as a scavenger of reactive oxygen species, which was corroborated with the % Ce3+ change quantified by X-ray photoelectron spectroscopy. The HA-Ag pellet shows antibacterial efficacy of ~61% for E. coli and ~53% for S. aureus, while a reduction of ~59% for E. coli and ~50% for S. aureus is observed for HA-ceria-2.5Ag pellet, affirming Ag reinforcement as an established bactericidal agent. The enhanced hydrophobicity on all the HA-based composites affords a high protein adsorption (24 h incubation). Further, elevated hFOB cell count (~6.7 times for HA-ceria-Ag on day 7) with filopodial extensions (60-150 µm) and matrix-like deposition reflect cell-substrate intimacy. Thus, synergistic antioxidant ceria and antibacterial Ag reinforcement with enhanced mechanical integrity can potentially serve as cytocompatible porous bone scaffolds or bioactive coatings on femoral stems.

Enhanced Tribological and Bacterial Resistance of Carbon Nanotube with Ceria- and Silver-Incorporated Hydroxyapatite Biocoating.

Pertaining to real-life applications (by scaling up) of hydroxyapatite (HA)-based materials, herein is a study illustrating the role of carbon nanotube (CNT) reinforcement with ceria (CeO2) and silver (Ag) in HA on titanium alloy (TiAl6V4) substrate, utilizing the plasma-spraying processing technique, is presented. When compared with pure HA coating enhanced hardness (from 2.5 to 5.8 GPa), elastic modulus (from 110 to 171 GPa), and fracture toughness (from 0.7 to 2.2 MPa·m1/2) elicited a reduced wear rate from 55.3 × 10-5 mm³·N-1·m-1 to 2.1 × 10-5 mm³·N-1·m-1 in HA-CNT-CeO2-Ag. Besides, an order of magnitude lower Archard's wear constant and a 41% decreased shear stress by for HA-CNT-CeO2-Ag coating depicted the effect of higher hardness and modulus of a material to control its wear phenomenon. Antibacterial property of 46% (bactericidal) is ascribed to Ag in addition to CNT-CeO2 in HA. Nonetheless, the composite coating also portrayed exaggerated L929 fibroblast cell growth (4.8 times more than HA), which was visualized as flat and elongated cells with multiple filopodial protrusions. Hence, synthesis of a material with enhanced mechanical integrity resulting in tribological resistance and cytocompatible efficacy was achieved, thereupon making HA-CNT-CeO2-Ag a scalable potent material for real-life load-bearing implantable bio-coating.