miRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population.

The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005-0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00-2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22-181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32-3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = -1.07), and miR-143 (Log2FC = -1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.

Dynamics of nanocluster aerosol in the indoor atmosphere during gas cooking.

Nanocluster aerosol (NCA: particles in the size range of 1-3 nm) are a critically important, yet understudied, class of atmospheric aerosol particles. NCA efficiently deposit in the human respiratory system and can translocate to vital organs. Due to their high surface area-to-mass ratios, NCA are associated with a heightened propensity for bioactivity and toxicity. Despite the human health relevance of NCA, little is known regarding the prevalence of NCA in indoor environments where people spend the majority of their time. In this study, we quantify the formation and transformation of indoor atmospheric NCA down to 1 nm via high-resolution online nanoparticle measurements during propane gas cooking in a residential building. We observed a substantial pool of sub-1.5 nm NCA in the indoor atmosphere during cooking periods, with aerosol number concentrations often dominated by the newly formed NCA. Indoor atmospheric NCA emission factors can reach up to ∼1016 NCA/kg-fuel during propane gas cooking and can exceed those for vehicles with gasoline and diesel engines. Such high emissions of combustion-derived indoor NCA can result in substantial NCA respiratory exposures and dose rates for children and adults, significantly exceeding that for outdoor traffic-associated NCA. Combustion-derived indoor NCA undergo unique size-dependent physical transformations, strongly influenced by particle coagulation and condensation of low-volatility cooking vapors. We show that indoor atmospheric NCA need to be measured directly and cannot be predicted using conventional indoor air pollution markers such as PM2.5 mass concentrations and NO x (NO + NO2) mixing ratios.

Helicobacter pylori-Associated Immune Thrombocytopenia: Diagnostic and Therapeutic Approach.

The relationship between immune thrombocytopenia (ITP) and Helicobacterpylori infection has largely been an unexplored entity. This review article aims at focusing on the role of H. pylori in secondary ITP. We also elucidated the importance of diagnostic workup and treatment of H. pylori in this article. The mechanisms of H. pylori-associated ITP have been covered in this article. The factors determining platelet response to H. pylori eradication therapy have been mentioned. It is extremely crucial to be aware that H. pylori is a major causative pathogen for new-onset ITP as well as chronic ITP. Upper gastrointestinal endoscopic biopsy is the best invasive method for the diagnosis of the same. Further studies need to be conducted across larger, more diverse groups to validate our observation that eradication of H. pylori could aid platelet recovery in ITP.

RésuméObjectif: La relation entre ITP et l'infection à Helicobacterpylori a largement été un domaine inexploré. Cet article de revue vise à SE concentrer sur le rôle de H. pylori dans l'ITP secondaire. Nous avons également élucidé l'importance du bilan diagnostique et du traitement de H. pylori dans cet article. Les mécanismes de l'ITP associée à H. pylori ont été abordés dans cet article. Les facteurs déterminant la réponse des plaquettes à la thérapie d'éradication de H. pylori ont été mentionnés. Il est extrêmement crucial de prendre conscience que H. pylori est un pathogène causal majeur pour l'ITP de novo ainsi que pour l'ITP chronique. La biopsie endoscopique du tractus gastro-intestinal supérieur est la meilleure méthode invasive pour le diagnostic de la même pathologie. Des études ultérieures doivent être menées auprès de groupes plus vastes et plus diversifiés pour valider notre observation selon laquelle l'éradication de H. pylori pourrait favoriser la récupération des plaquettes dans l'ITP.

One-stage prosthodontically driven jaw reconstruction in patients with benign and malignant pathologies: A 7- to 11-year cohort study.

OBJECTIVES: One stage functional jaw reconstruction is defined as the resection and reconstruction of segmental defects in conjunction with the placement of dental implants in an ideal prosthetic position and loaded with a provisional restoration, during one surgical procedure. The aim of the study is to describe clinical outcomes of patients who underwent one stage functional jaw reconstruction. METHODS: Patients who underwent one-stage functional jaw reconstruction, from January 2013 to March 2016 were recalled in 2022 and 2023. Planning and execution for the reconstruction utilized either analogue or digital techniques. Outcome parameters recorded were treatment-related outcomes at patient level, implant-related outcomes and patient-reported outcome measures. RESULTS: Eighteen patients underwent one-stage jaw reconstruction with a total of 57 implants. Four patients had maxillary and 14 had mandibular reconstructions. Ten patients underwent postoperative radiotherapy. Ten patients were planned using analogue and eight by digital planning. Three patients had partial flap necrosis, three patients had plate fractures, implant loss was seen in one patient and four patients died during the period. A functional prosthesis was provided in 16 out of the 18 patients. CONCLUSION: One-stage functional jaw reconstruction is a predictable method for providing rehabilitation with successful outcomes at 7-11 years. However, caution should be exercised when the treatment modality is carried out in patients with malignant pathologies who have undergone radiotherapy.

Low ppm NO2 detection through advanced ultrasensitive copper oxide gas sensor.

The imperative development of a cutting-edge environmental gas sensor is essential to proficiently monitor and detect hazardous gases, ensuring comprehensive safety and awareness. Nanostructures developed from metal oxides are emerging as promising candidates for achieving superior performance in gas sensors. NO2 is one of the toxic gases that affects people as well as the environment so its detection is crucial. The present study investigates the gas sensing capability of copper oxide-based sensor for 5 ppm of NO2 gas at 100 °C. The sensing material was synthesized using a facile precipitation method and characterized by XRD, FE-SEM, UV-visible spectroscopy, photoluminescence spectroscopy, XPS and BET techniques. The developed material shows a response equal to 67.1% at optimal temperature towards 5 ppm NO2 gas. The sensor demonstrated an impressive detection limit of 300 ppb, along with a commendable percentage response of 5.2%. Under optimized conditions, the synthesized material demonstrated its high selectivity, as evidenced by the highest percentage response recorded for NO2 gas among NO2, NH3, CO, CO2 and H2S.

"The impact of orthognathic surgery on articulation proficiency and speech intelligibility in skeletal Class III malocclusion: 18 months follow up".

Introduction: Orthognathic surgery results in the positional change of the maxilla and mandible that may affect speech. The present study evaluated the effect of combined maxillary advancement and mandibular setback surgery on articulation proficiency and speech intelligibility in patients with non-syndromic skeletal Class III malocclusion. Methods: In this prospective study, twenty-five patients with skeletal class III malocclusion and consecutively treated with Lefort-1 maxillary advancement and mandibular setback (BSSO) orthognathic surgery were included in this study. The speech sample was recorded with a digital audio tape recorder one day before surgery and at 3, 6, 9, 12 and 18 months after surgery. Three qualified and experienced speech and language pathologists evaluated articulation errors and intelligibility of speech samples. Repeated One-way analysis of variance was used to compare articulation proficiency and speech intelligibility at different time intervals. Results: The substitution, omission, distortion and addition errors showed no significant changes at 3 months and 6 months. The total articulation errors decreased to zero at 9 months and no significant increase was observed till 18 months (P < 0.05). Speech intelligibility showed statistically non-significant improvement at any time interval. Cephalometric skeletal parameters SNA and N l A°. were significantly correlated with addition and total articulation errors at 18 months follow up. Conclusions: The ortho-surgical treatment improves speech (decreases. articulation errors) in most of the patients usually 6-9 months post-surgery. Speech intelligibility is not affected by bimaxillary orthognathic surgery in skeletal class III patients. The articulation errors were correlated to changes in position of maxilla.

Sodium Alginate Chitosan Crosslinked Hydrogel Amoxycillin Absorption Properties.

Wound healing refers to the replacement of destroyed or damaged tissue of a living organism by newly produced tissue, and the time taken is known as wound regeneration time. Wound care is a major challenging biomedical field due to the delayed healing process or delayed wound regeneration time. The factors responsible for delayed wound healing are poor oxygen flow, less exposure to moisture, diseases such as diabetes and cancer, etc., Wound dressings that are formulated from biopolymers such as chitosan, chitin, and cellulose have properties such as biocompatibility (compatible with living systems and does not cause any immunological rejection), biodegradable, nontoxic with minimal side effects, anti-microbial, anti-inflammatory properties. Chitosan is obtained from scales of fish and shrimp. It contains highly reactive amine groups and sodium alginate, which is a polysaccharide produced from seaweed and bacteria and is biocompatible with living systems and biodegradable polysaccharides. This study is based on the development of sodium alginate crosslinked hydrogel and testing the properties of hydrogel with amoxycillin drug and water release property of the drug.

Engineered lignocellulosic based biochar to remove endocrine-disrupting chemicals: Assessment of binding mechanism.

The safety and health of aquatic organisms and humans are threatened by the increasing presence of pollutants in the environment. Endocrine disrupting chemicals are common pollutants which affect the function of endocrine and causes adverse effects on human health. These chemicals can disrupt metabolic processes by interacting with hormone receptors upon consumptions by humans or aquatic species. Several studies have reported the presence of endocrine disrupting chemicals in waterbodies, food, air and soil. These chemicals are associated with increasing occurrence of obesity, metabolic disorders, reproductive abnormalities, autism, cancer, epigenetic variation and cardiovascular risk. Conventional treatment processes are expensive, not environment friendly and unable to achieve complete removal of these harmful chemicals. In recent years, biochar from different sources has gained a considerable interest due to their adsorption efficiency with porous structure and large surface areas. biochar derived from lignocellulosic biomass are widely used as sustainable catalysts in soil remediation, carbon sequestration, removal of organic and inorganic pollutants and wastewater treatment. This review conceptualizes the production techniques of biochar from lignocellulosic biomass and explores the functionalization and interaction of biochar with endocrine-disrupting chemicals. This review also identifies the further needs of research. Overall, the environmental and health risks of endocrine-disrupting chemicals can be dealt with by biochar produced from lignocellulosic biomass as a sustainable and prominent approach.

Hazard identification of endocrine-disrupting carcinogens (EDCs) in relation to cancers in humans.

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

Rehabilitation of Reconstructed Maxilla Using Denture-Guided Epithelial Regeneration in DCIA Flap: 10-Year Follow-Up.

This 10-year follow-up report describes the interdisciplinary comprehensive management of a patient with aneurysmal bone cyst of the maxilla in a 24-year-old patient. The treatment included resection and primary reconstruction with vascularized deep circumflex iliac artery-based composite free flap, implant placement, and peri-implant soft tissue management using denture-guided epithelial regeneration with interim dentures. Definitive management was done using implant-supported cast partial dentures, and the patient followed up for 10 years.

In Vitro and In Vivo Investigations of Chromone Derivatives as Potential Multitarget-Directed Ligands: Cognitive Amelioration Utilizing a Scopolamine-Induced Zebrafish Model.

Alzheimer's disease is a complex neurological disorder linked with multiple pathological hallmarks. The interrelation of therapeutic targets assists in the enhancement of cognitive decline through interference with overall neuronal transmission. We have synthesized and screened various chromone derivatives as potential multitarget-directed ligands for the effective treatment of Alzheimer's disease. The synthesized compounds exhibited multipotent activity against AChE, BuChE, MAO-B, and amyloid ß aggregation. Three potent compounds, i.e., VN-3, VN-14, and VN-19 were identified that displayed remarkable activities against different targets. These compounds displayed IC50 values of 80 nM, 2.52 µM, and 140 nM against the AChE enzyme, respectively, and IC50 values of 2.07 µM, 70 nM, and 450 nM against the MAO-B isoform, respectively. VN-3 displayed potent activity against self-induced Aß1-42 aggregation with inhibition of 58.3%. In the ROS inhibition studies, the most potent compounds reduced the intracellular ROS levels up to 80% in SH-SY5Y cells at 25 µM concentration. The compounds were found to be neuroprotective and noncytotoxic even at a concentration of 25 µM against SH-SY5Y cells. In silico studies showed that the compounds were nicely accommodated in the active sites of the receptors along with thermodynamically stable orientations. Compound VN-19 exhibited a balanced multitargeting profile against AChE, BuChE, MAO-B, and Aß1-42 enzymes and was further evaluated for in vivo activities on the scopolamine-induced zebrafish model. VN-19 was found to ameliorate the cognitive decline in zebrafish brains by protecting them against scopolamine-induced neurodegeneration. Thus, VN-3, VN-14, and VN-19 were identified as potent multitarget-directed ligands with a balanced activity profile against different targets and can be developed as therapeutics for AD.

Neoantigen Identification and Dendritic Cell-Based Vaccines for Lung Cancer Immunotherapy.

Immunotherapies can treat many cancers, including difficult-to-treat cases such as lung cancer. Due to its tolerability, long-lasting therapeutic responses, and efficacy in a wide spectrum of patients, immunotherapy can also help to treat lung cancer, which has few treatment choices. Tumor-specific antigens (TSAs) for cancer vaccinations and T-cell therapies are difficult to discover. Neoantigens (NeoAgs) from genetic mutations, irregular RNA splicing, protein changes, or viral genetic sequences in tumor cells provide a solution. NeoAgs, unlike TSAs, are non-self and can cause an immunological response. Next-generation sequencing (NGS) and bioinformatics can swiftly detect and forecast tumor-specific NeoAgs. Highly immunogenic NeoAgs provide personalized or generalized cancer immunotherapies. Dendritic cells (DCs), which originate and regulate T-cell responses, are widely studied potential immunotherapeutic therapies for lung cancer and other cancers. DC vaccines are stable, reliable, and safe in clinical trials. The purpose of this article is to evaluate the current status, limitations, and prospective clinical applications of DC vaccines, as well as the identification and selection of major histocompatibility complex (MHC) class I and II genes for NeoAgs. Our goal is to explain DC biology and activate DC manipulation to help researchers create extremely potent cancer vaccines for patients.

Early Detection of Oral Potentially Malignant Disorders: A Review on Prospective Screening Methods with Regard to Global Challenges.

Oral cancer is a cancer type that is widely prevalent in low-and middle-income countries with a high mortality rate, and poor quality of life for patients after treatment. Early treatment of cancer increases patient survival, improves quality of life and results in less morbidity and a better prognosis. To reach this goal, early detection of malignancies using technologies that can be used in remote and low resource areas is desirable. Such technologies should be affordable, accurate, and easy to use and interpret. This review surveys different technologies that have the potentials of implementation in primary health and general dental practice, considering global perspectives and with a focus on the population in India, where oral cancer is highly prevalent. The technologies reviewed include both sample-based methods, such as saliva and blood analysis and brush biopsy, and more direct screening of the oral cavity including fluorescence, Raman techniques, and optical coherence tomography. Digitalisation, followed by automated artificial intelligence based analysis, are key elements in facilitating wide access to these technologies, to non-specialist personnel and in rural areas, increasing quality and objectivity of the analysis while simultaneously reducing the labour and need for highly trained specialists.

Cloning, expression, and characterization of a novel thermo-acidophilic l-asparaginase of Pseudomonas aeruginosa CSPS4.

In the present investigation, a soil isolate Pseudomonas aeruginosa CSPS4 was used for retrieving the l-asparaginase encoding gene (Asn_PA) of size 1089 bp. The gene was successfully cloned into the pET28a (+) vector and expressed into E. coli BL21(DE3) for characterization of the protein. The recombinant rAsn_PA enzyme was purified by affinity chromatography using Ni-NTA2+ resins. Molecular weight analysis using SDS-PAGE unveiled rAsn_PA as a monomeric protein of molecular weight ~ 35 kDa. On characterization, the recombinant rAsn_PA showed optimum pH and temperature of 6.0 and 60 °C, respectively, along with significant stability at 50-70 °C, along with 50% residual activity at 80 °C after 3 h of incubation. Similarly, the rAsn_PA exhibited asparaginase activity over a broad pH range between 4 and 8. The enzyme was not significantly inhibited in the presence of detergents. The rAsn_PA was grouped into the asparaginase-glutaminase family II due to the glutaminase activity. The purified rAsn_PA showed antitumor activity by exhibiting a cytotoxic effect on three different cell lines, where IC50 of purified rAsn_PA was 2.3 IU, 3.7 IU, and 20.5 IU for HL-60, MOLM-13, and K-562 cell lines, respectively. Thus, recombinant rAsn_PA of P. aeruginosa CSPS4 may also be explored as an antitumor agent after reducing or minimizing the glutaminase activity. Thermo-acidophilic properties of rAsn_PA make it a novel enzyme that needs to be further investigated.

Clinicodemographic profile, management, and treatment outcomes in advanced retinoblastoma at a tertiary care center in North India.

PURPOSE: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. METHODS: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. RESULTS: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. CONCLUSION: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

Recurrent spontaneous subluxation of the eye globe managed with orbital decompression: A case report with literature review.

Spontaneous subluxation of the eyeball is a rare phenomenon as there are only few cases reported in the literature. It is a sight-threatening condition and very traumatising for the patient. The globe has to be reposited back within the socket immediately to save vision and to prevent exposure keratitis and optic neuropathy. In all published reports about subluxation of the eyeball, the underlying aetiology which was responsible for this condition was found. Herein, we report a case of recurrent spontaneous subluxation of the eyeball in which the cause could not be ascertained in a middle-aged male patient even after thorough clinical examination and investigation. The case was managed successfully with three-wall orbital decompression and tarsorrhaphy. The patient did not experience any episode of subluxation of the globe following surgery as orbital decompression increased the available space for the orbital contents, thereby averting its occurrence.

Cancer Vaccines in the Immunotherapy Era: Promise and Potential.

Therapeutic vaccines are a promising alternative for active immunotherapy for different types of cancers. Therapeutic cancer vaccines aim to prevent immune system responses that are not targeted at the tumors only, but also boost the anti-tumor immunity and promote regression or eradication of the malignancy without, or with minimal, adverse events. Clinical trial data have pushed the development of cancer vaccines forward, and the US Food and Drug Administration authorized the first therapeutic cancer vaccine. In the present review, we discuss the various types of cancer vaccines and different approaches for the development of therapeutic cancer vaccines, along with the current state of knowledge and future prospects. We also discuss how tumor-induced immune suppression limits the effectiveness of therapeutic vaccinations, and strategies to overcome this barrier to design efficacious, long-lasting anti-tumor immune responses in the generation of vaccines.