Activated PI3Kδ Specifically Perturbs Mouse Regulatory T Cell Homeostasis and Function Leading to Immune Dysregulation.

FOXP3+ regulatory T cells (Treg) are required for maintaining immune tolerance and preventing systemic autoimmunity. PI3Kδ is required for normal Treg development and function. However, the impacts of dysregulated PI3Kδ signaling on Treg function remain incompletely understood. In this study, we used a conditional mouse model of activated PI3Kδ syndrome to investigate the role of altered PI3Kδ signaling specifically within the Treg compartment. Activated mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) specifically within the Treg compartment exhibited weight loss and evidence for chronic inflammation, as demonstrated by increased memory/effector CD4+ and CD8+ T cells with enhanced IFN-γ secretion, spontaneous germinal center responses, and production of broad-spectrum autoantibodies. Intriguingly, aPIK3CD facilitated Treg precursor development within the thymus and an increase in peripheral Treg numbers. Peripheral Treg, however, exhibited an altered phenotype, including increased PD-1 expression and reduced competitive fitness. Consistent with these findings, Treg-specific aPIK3CD mice mounted an elevated humoral response following immunization with a T cell-dependent Ag, which correlated with a decrease in follicular Treg. Taken together, these findings demonstrate that an optimal threshold of PI3Kδ activity is critical for Treg homeostasis and function, suggesting that PI3Kδ signaling in Treg might be therapeutically targeted to either augment or inhibit immune responses.

Evidence-based effectiveness of Ozone therapy in the treatment for oral lichen planus - A systematic review.

Oral lichen planus is a common, chronic mucocutaneous condition of uncertain origin. Early treatment of OLP can dramatically reduce the risk of further development, which in turn reduces the risk of developing cancer. Numerous methods can be used to treat OLP. Since the significance of ozone in treating this disease is still uncertain. This systematic review was conducted based on english databases, including PUBMED, SCOPUS, Embase, Ovid, and Journal of Web up to July 2022. We used the search phrases "ozone," "ozone in the treatment of oral lichen planus," "oral lichen planus," and "ozone therapy." Finally, five papers were selected for qualitative analysis. This review included a total of five papers, four of which were clinical trials and one was a longitudinal study. All studies included the erosive form of OLP, also ozone therapy was applied to patients who did not respond to conventional treatment. Ozone showed significant therapeutic effects in terms of reduction in pain and size of the lesion. The signs and symptoms associated with OLP such as burning sensation, lesion size, and scarring all considerably improved with ozone therapy.

The immediate impact of mandatory helmet law on maxillo-facial trauma: A comparative study in a major trauma center, Uttar Pradesh.

Aim: To analyze the effect of the mandatory helmet rule in helmet usage among motorcycle riders and on facial trauma and to determine the significance of difference in the possibility of facial trauma between the helmeted and non-helmeted motorcycle riders. Setting and Design: A retrospective comparative study conducted in a major trauma center at Uttar Pradesh. Material and Method: Data for the present study was obtained from records of the Emergency Department of Trauma Center, for a period of two months before and after the implementation of The Motor Vehicles Act in UP. The study included patients with a history of non-fatal motorcycle accidents who sustained facial injuries regardless of the presence of injuries to other areas of the body during the study period. Information regarding helmet usage during the accident was also recorded. The results were compared between the pre-law period and post-law period. Statistical Analysis Used: Sample t-test was applied to find the level of significance. Results: Out of 219 injured patients, 152 (69.40%) subjects were not wearing helmets, whereas only 67 (30.59%) subjects were wearing helmets. It was observed that around 68.18% of people stated wearing helmets after law implementation with a statistical significance (P value < 0.05). Conclusion: Our study shows that the mandatory helmet rule with elevated penalty rates has significantly increased the usage of helmet among the motorcycle riders, and it also proves that the possibility of facial trauma is significantly higher in non-helmeted riders when compared to helmeted riders.

Methemoglobinemia Following Indoxacarb Ingestion: A Unique Toxicological Presentation.

Indoxacarb, an oxadiazine insecticide, is known for its selective lethality by blocking neuronal voltage-dependent sodium channels. While primarily developed to target insect populations resistant to other pesticides, its toxicity in humans remains poorly understood. We present a case of methemoglobinemia resulting from indoxacarb ingestion, a rare manifestation of its toxic effects. A 38-year-old farmer attempted suicide by ingesting the insecticide, leading to cyanosis, hypoxemia, and characteristic arterial blood gas findings indicative of methemoglobinemia. Prompt diagnosis was challenging due to the absence of specific tests, necessitating clinical suspicion. Treatment with methylene blue and supportive therapy resulted in significant clinical improvement, highlighting the importance of early intervention in managing indoxacarb poisoning. This case underscores the need for increased awareness among healthcare providers regarding the potential toxic effects of indoxacarb. It emphasizes the importance of prompt recognition and treatment of methemoglobinemia in pesticide-related poisonings. Further research is warranted to elucidate the mechanisms underlying indoxacarb toxicity in humans and to optimize treatment strategies for affected individuals.

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities.

The essential amino acid histidine plays a central role in the manifestation of several metabolic processes, including protein synthesis, enzyme-catalysis, and key biomolecular interactions. However, excess accumulation of histidine causes histidinemia, which shows brain-related medical complications, and the molecular mechanism of such histidine-linked complications is largely unknown. Here, we show that histidine undergoes a self-assembly process, leading to the formation of amyloid-like cytotoxic and catalytically active nanofibers. The kinetics of histidine self-assembly was favored in the presence of Mg(II) and Co(II) ions. Molecular dynamics data showed that preferential noncovalent interactions dominated by H-bonds between histidine molecules facilitate the formation of histidine nanofibers. The histidine nanofibers induced amyloid cross-seeding reactions in several proteins and peptides including pathogenic Aß1-42 and brain extract components. Further, the histidine nanofibers exhibited oxidase activity and enhanced the oxidation of neurotransmitters. Cell-based studies confirmed the cellular internalization of histidine nanofibers in SH-SY5Y cells and subsequent cytotoxic effects through necrosis and apoptosis-mediated cell death. Since several complications including behavioral abnormality, developmental delay, and neurological disabilities are directly linked to abnormal accumulation of histidine, our findings provide a foundational understanding of the mechanism of histidine-related complications. Further, the ability of histidine nanofibers to catalyze amyloid seeding and oxidation reactions is equally important for both biological and materials science research.

Persistent facial pain in post-stroke patients, a hospital-based cohort study; experience from North India.

Background: Post-stroke pain is common after a stroke and might be underreported. We describe Persistent Facial Pain (PFP) developed in post-stroke patients. Method: ology: This was a prospective hospital-based cohort study of stroke patients, and patients were followed up. Out of 415 stroke patients, 26 developed PFP. Result: Out of all PFP patients, six patients had an ischemic stroke, and 20 had a hemorrhagic stroke. 57.7% of patients had hypertension, while 34.6 patients had diabetes. The stroke location was left-sided in 12 patients and right-sided in 14 patients. 46.15% of patients responded to venlafaxine, 30.77% responded to amitriptyline, and 23.08% responded to pregabalin. Conclusion: Persistent facial pain is a pain syndrome that might be missed in patients post-stroke. It might be more common in hemorrhagic stroke patients than in ischemic stroke patients. It responds adequately to antidepressants. A high index of suspicion is required to diagnose and appropriately manage these patients.

Prehospital Cervical Spine (C-spine) Stabilization and Airway Management in a Trauma Patient: A Review.

Severe traumatic damage to the brain-to-body signaling bundle that results in bruising and a partial or total tear of the spinal cord is known as a spinal cord injury (SCI). SCI may develop at the time of an event or after. It can also develop while handling the patient and can worsen during the transportation of the patient. So prehospital care is crucial to prevent or minimize SCI. Prehospital care involves examining the patient, immobilizing the cervical spine (C-spine), providing cardiovascular support (keeping the mean arterial blood pressure over 85 mmHg), and carefully managing the airway (possibly intubating the patient using manual in-line stabilization (MILS)). Methylprednisolone (MPS) and other pharmacological treatments have not been shown to offer clinically meaningful and essential benefits for people with SCI. The therapeutic use of MPS in patients with SCI in the prehospital context is no longer supported. Additionally, whether or not pharmaceutical drugs will be effective in therapeutic hypothermia is unknown. When performing endotracheal intubation on these patients, the potential for C-spine damage is always considered. During intubation, the MILS approach significantly reduces C-spine movement. The MILS method, however, can potentially restrict mouth opening and result in subpar laryngoscopic vision. These issues can be handled using the recently developed video laryngoscope, such as Airtraq laryngoscope and AirWay Scope (AWS). Compared to a direct laryngoscope, the AWS and Airtraq laryngoscope reduced the improvement of intubation conditions and the acceleration of tracheal intubation through the occiput-C1 and C2-C4 levels of the C-spine extension movement.

Automated Synthesis of [11C]PiB via [11CH3OTf]-as Methylating Agent for PET Imaging of ß-Amyloid.

AIM: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor. BACKGROUND: [11C]PiB is a promising radiotracer for PET imaging of ß-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was by the quality and safety criteria required for clinical use. METHODS: The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life. RESULTS: The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/µmol range. CONCLUSION: A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

Electromyographic Assessment of Masticatory Muscles & their Asymmetries in Adult Indian Population.

Objective: To study the surface electromyography (sEMG) and it is asymmetry under resting and dynamic conditions in masticatory muscles. Materials and Methods: sEMG of the masticatory muscles (bilateral masseter & temporalis) was done in 61 healthy subjects (mean age 28.5 ± 8.8 years) with bilateral functional molar occlusal relationship. Root mean square (RMS) values sEMG for each activity (rest, clenching, maximum mouth opening (MMO), left and right excursion) for a 10 s period were recorded and analyzed. Indices for asymmetry of muscles, relative activity and resultant torque were assessed and analyzed. Results: RMS values of sEMG during clenching were significantly higher for all masticatory muscles in males compared to females (p < 0.05). During excursive mandibular movement a statistically significant difference seen in ipsilateral temporalis muscle in males. sEMG of masticatory muscles during rest as well as functional activities of mandible was asymmetrical. A predominant masseteric activity was observed for all functional activities of mandible except during rest for which temporalis muscle activity was higher. Right sided torque was observed during rest, MMO and right lateral movements while a predominant left sided torque was present during left lateral movement and clenching. Conclusion: sEMG values of masticatory muscles obtained in our study can be used as reference for healthy Indian population. A perfect muscular symmetry might be illusive and a controlled asymmetry criterion appears to be more useful which corresponds to reality.

Biotechnological innovations in nanocellulose production from waste biomass with a focus on pineapple waste.

New materials' synthesis and utilization have shown many critical challenges in healthcare and other industrial sectors as most of these materials are directly or indirectly developed from fossil fuel resources. Environmental regulations and sustainability concepts have promoted the use of natural compounds with unique structures and properties that can be biodegradable, biocompatible, and eco-friendly. In this context, nanocellulose (NC) utility in different sectors and industries is reported due to their unique properties including biocompatibility and antimicrobial characteristics. The bacterial nanocellulose (BNC)-based materials have been synthesized by bacterial cells and extracted from plant waste materials including pineapple plant waste biomass. These materials have been utilized in the form of nanofibers and nanocrystals. These materials are found to have excellent surface properties, low density, and good transparency, and are rich in hydroxyl groups for their modifications to other useful products. These materials are well utilized in different sectors including biomedical or health care centres, nanocomposite materials, supercapacitors, and polymer matrix production. This review explores different approaches for NC production from pineapple waste residues using biotechnological interventions, approaches for their modification, and wider applications in different sectors. Recent technological developments in NC production by enzymatic treatment are critically discussed. The utilization of pineapple waste-derived NC from a bioeconomic perspective is summarized in the paper. The chemical composition and properties of nanocellulose extracted from pineapple waste may have unique characteristics compared to other sources. Pineapple waste for nanocellulose production aligns with the principles of sustainability, waste reduction, and innovation, making it a promising and novel approach in the field of nanocellulose materials.

Development of "Smart Foods" for health by nanoencapsulation: Novel technologies and challenges.

Importance of nanotechnology may be seen by penetration of its application in diverse areas including the food sector. With investigations and advancements in nanotechnology, based on feedback from these diverse areas, ease, and efficacy are also increasing. The food sector may use nanotechnology to encapsulate smart foods for increased health, wellness, illness prevention, and effective targeted delivery. Such nanoencapsulated targeted delivery systems may further add to the economic and nutritional properties of smart foods like stability, solubility, effectiveness, safeguard against disintegration, permeability, and bioavailability of smart/bioactive substances. But in the way of application, the fabrication of nanomaterials/nanostructures has several challenges which range from figuring out the optimal technique for obtaining them to determining the most suitable form of nanostructure for a bioactive molecule of interest. This review precisely addresses concepts, recent advances in fabrication techniques as well as current challenges/glitches of nanoencapsulation with special reference to smart foods/bioactive components. Since dealing with food materials also raises the quest for safety and regulatory norms a brief overview of the safety and regulatory aspects of nanomaterials/nanoencapsulation is also presented.

Robust Optical Detection of Ga3+ by a Rhodamine- and Coumarin-Based Proficient Probe: Theoretical Investigations and Biological Applications.

The present investigation highlights a rhodamine-B- and coumarin-based efficient probe that selectively detects Ga3+ over other metal ions. The active pocket of the ligand for trapping the metal ions and the binding stoichiometry of its Ga3+ complex were discovered by single-crystal X-ray diffraction (SC-XRD) analysis. This binding stoichiometry was further confirmed in the solution state by mass spectrometry and Job's plot. The detection limit was found to be at the nanomolar level. Pyrophosphate being a well-known quencher could easily quench the fluorescence intensity of the RC in the presence of Ga3+ and reversibly recognize Ga3+ in the solution. The spiro ring opening of the ligand after Ga3+ insertion is proposed to be the principal mechanism for the turn-on fluorescence response. This ring opening was confirmed by SC-XRD data and nuclear magnetic resonance (NMR) titration experiments. Both ground- and excited-state calculations of the ligand and complex have been carried out to obtain information about their energy levels and to obtain the theoretical electronic spectra. Furthermore, the live-cell imaging of the probe only and the probe after the addition of Ga3+ have been carried out in HaCaT cells and satisfactory responses were observed. Interestingly, with the help of this probe, Ga3+ can be tracked inside the intracellular organelle such as lysosomes along with other regions of the cell. The article highlights a rhodamine-coumarin-based probe for the detection of Ga3+ over other metal ions with a nanomolar level detection limit. Structural characterization of the ligand and its Ga3+ complex was investigated by SC-XRD. Density functional theory (DFT) and time-dependent DFT (TD-DFT) studies were carried out to explore the excited-state energies and electronic spectra. The application of the probe for the detection of Ga3+ in live cells has been explored, and positive responses were observed.

Comparative Evaluation of Nasolabial Flap, Buccal Fat Pad and Platysma Myocutaneous Flap for Reconstruction of Oral Sub Mucous Fibrosis Defects.

Moderately advanced (stage III) and advanced (stage IV a & b) OSMF requires surgical intervention for management A number of options are available for reconstruction of post OSMF oral cavity defects. In our study we retrospectively compared buccal fat pad, nasolabial flap and platysma flap for reconstruction of the buccal mucosal defects. Patient records were obtained from the medical records section of the Institute and divided into three groups; group A (buccal fat pad), group B (nasolabial group) and group C (platysma flap). Maximal mouth opening and intercommisural distance were the primary outcomes. Kruskal Wallis test was used to test the mean difference between three groups. Mann-Whitney test was used for intergroup comparisons. Wilcoxon signed rank test was used to evaluate the mean difference in outcomes at each follow up interval. A p value of < 0.05 was considered as statistically significant at 95% confidence interval. After 1 year follow up patients in platysma group had significantly better mouth opening (39.84 ± 1.65 mm) compared to both buccal fat pad (36.69 ± 3.41 mm) and nasolabial groups (37.94 ± 0.43 mm). Inter commisural distance was significantly better in patients reconstructed with platysma flap (59.21 ± 0.99 mm) compared to both buccal fat pad (54.11 ± 1 mm) and nasolabial flap (56.84 ± 1.48 mm). Platysma flap lead to significantly better maximal mouth opening compared to both nasolabial and buccal fat pad. Both buccal fat pad and nasolabial lead to comparable mouth opening. Inter commissural distance is maximum with platysma flap followed by nasolabial flap and buccal fat pad.

Analysis of Auxin-Encoding Gene Family in Vigna radiata and It's Cross-Species Expression Modulating Waterlogging Tolerance in Wild Vigna umbellata.

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5, VrARF-11, VrARF-25, and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress.

Study of paraCEST response on six-coordinated Co(II) and Ni(II) complexes of a pyridine-tetraamide-based ligand.

This study highlights the successful synthesis of a potential ligand, 2,2',2'',2'''-((pyridine-2,6-diylbis(methylene))bis(azanetriyl))tetraacetamide (PATA), along with its corresponding Co(II) and Ni(II) complexes for paraCEST-based agents. X-ray diffraction data confirmed that both the complexes are six coordinated with distorted octahedral geometries, but only the [Co(PATA)]2+ complex has a good structural feature to show paraCEST activity. After a thorough characterization of the ligand and both of its complexes, various studies, including solution-state magnetic properties, redox properties, temperature, and pH variation studies, were carried out. [Co(PATA)]2+ remained inert in the presence of competing ions, under acidic conditions, at high temperatures, and in the physiological pH range. The paraCEST response of [Co(PATA)]2+ has been measured in the presence of HEPES buffer medium, and a high paraCEST feature was discovered at both 37 and 25 °C. The pH variation paraCEST studies were carried out and the exchange rate constant of the probe at 37 and 25 °C was also determined. However, due to the fast exchange of water protons, the [Ni(PATA)(OH2)]2+ complex remained inactive in the CEST process.

Advancements and Challenges in Developing Malaria Vaccines: Targeting Multiple Stages of the Parasite Life Cycle.

Malaria, caused by Plasmodium species, remains a major global health concern, causing millions of deaths annually. While the introduction of the RTS,S vaccine has shown promise, there is a pressing need for more effective vaccines due to the emergence of drug-resistant parasites and insecticide-resistant vectors. However, the complex life cycle and genetic diversity of the parasite, technical obstacles, limited funding, and the impact of the 2019 pandemic have hindered progress in malaria vaccine development. This review focuses on advancements in malaria vaccine development, particularly the ongoing clinical trials targeting antigens from different stages of the Plasmodium life cycle. Additionally, we discuss the rationale, strategies, and challenges associated with vaccine design, aiming to enhance the immune response and protective efficacy of vaccine candidates. A cost-effective and multistage vaccine could hold the key to controlling and eradicating malaria.

Comparative paraCEST effect of amide and hydroxy groups in divalent cobalt and nickel complexes of tripyridine-based ligands.

Co(II) and Ni(II) complexes of two tri-pyridine-based ligands with two hydroxy and two amide exchangeable protons (TDTA) and with six amide exchangeable protons (TMTP) were investigated for application as paraCEST-based magnetic resonance imaging (MRI) contrast agents. The two hydroxy groups present in the TDTA ligand were found to be passive while the amide group was active towards the CEST process. In the case of the Co(II) and Ni(II) complexes of the TMTP ligand, all three coordinated amide groups participated in the exchange process, and excellent CEST signals were observed. The X-ray structure of the four complexes revealed the seven-coordinate geometry of Co(II) complexes and the six-coordinate geometry of Ni(II) complexes. The presence of amide protons and hydroxy protons in the complexes was detected by the NMR method. The stability of the complexes in solution at high temperatures, in different pH ranges and acidic conditions, in the presence of competing cations, and biologically relevant anions was investigated. Potentiometric titrations were carried out to determine the ligand's protonation constants and the complexes' thermodynamic stability constant at 25.0 °C and I = 0.15 mol L-1 NaClO4. ParaCEST studies of [Co(TMTP)]2+ and [Ni(TMTP)]2+ at variable pH and variable pulse power are highlighted.