ABSTRACT
The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 µg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs.
Subject(s)
Anti-Bacterial Agents , Benzimidazoles , Coumarins , Microbial Sensitivity Tests , Animals , Humans , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Benzimidazoles/chemical synthesis , Cell Survival/drug effects , Coumarins/chemistry , Coumarins/pharmacology , Coumarins/chemical synthesis , Dose-Response Relationship, Drug , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Klebsiella pneumoniae/drug effects , Molecular Structure , Structure-Activity RelationshipABSTRACT
BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development.
Subject(s)
Angelman Syndrome , Brain , Disease Models, Animal , Metabolomics , Proton Magnetic Resonance Spectroscopy , Animals , Angelman Syndrome/metabolism , Angelman Syndrome/genetics , Brain/metabolism , Brain/diagnostic imaging , Mice , Metabolome , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , FemaleABSTRACT
The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and in cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). While ZEB1 in tumor cells regulates metastasis and therapy resistance, its role in CAFs is largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis is accelerated, whereas invasion and metastasis in sporadic cancers are reduced. Single-cell transcriptomics, histological characterization, and in vitro modeling reveal a crucial role of ZEB1 in CAF polarization, promoting myofibroblastic features by restricting inflammatory activation. Zeb1 deficiency impairs collagen deposition and CAF barrier function but increases NFκB-mediated cytokine production, jointly promoting lymphocyte recruitment and immune checkpoint activation. Strikingly, the Zeb1-deficient CAF repertoire sensitizes to immune checkpoint inhibition, offering a therapeutic opportunity of targeting ZEB1 in CAFs and its usage as a prognostic biomarker. Collectively, we demonstrate that ZEB1-dependent plasticity of CAFs suppresses anti-tumor immunity and promotes metastasis.
Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Immunotherapy , Inflammation , Zinc Finger E-box-Binding Homeobox 1 , Zinc Finger E-box-Binding Homeobox 1/metabolism , Zinc Finger E-box-Binding Homeobox 1/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/therapy , Colorectal Neoplasms/immunology , Animals , Mice , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Humans , Inflammation/metabolism , Inflammation/genetics , Inflammation/pathology , Immunotherapy/methods , Gene Expression Regulation, Neoplastic , Fibroblasts/metabolism , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Epithelial-Mesenchymal Transition/geneticsABSTRACT
In this work, a common-path optical coherence tomography (OCT) system is demonstrated for characterizing the tissue in terms of some optical properties. A negative axicon structure chemically etched inside the fiber tip is employed as optical probe in the OCT. This probe generates a quality Bessel beam owning a large depth-of-field, â¼700 µm and small central spot size, â¼3 µm. The OCT system is probing the sample without using any microscopic lens. For experimental validation, the OCT imaging of chicken tissue has been obtained along with estimation of its refractive index and optical attenuation coefficient. Afterwards, the cancerous tissue is differentiated from the normal tissue based on the OCT imaging, refractive index, and optical attenuation coefficient. The respective tissue samples are collected from the human liver and pancreas. This probe could be a useful tool for endoscopic or minimal-invasive inspection of malignancy inside the tissue either at early-stage or during surgery.
Subject(s)
Chickens , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Tomography, Optical Coherence/instrumentation , Humans , Animals , Equipment Design , Liver/diagnostic imaging , Liver/pathology , Pancreas/diagnostic imaging , RefractometryABSTRACT
BACKGROUND: The maintenance of oral hygiene and subsequent health related issues in visually handicapped children is a challenging task. Hence, tools must be used to ensure good oral health in these children. The study aimed to analyze the effectiveness of preventive programs on oral health using specialized audio and tactile aids in visually impaired school children. MATERIALS AND METHODS: 100 visually handicapped children were selected for the study. They were divided into two groups: Group A (Training using Braille) and Group B (training by means of audio aids). Children were trained using appropriate tools and oral health was assessed using Plaque and Gingival bleeding indices. STATISTICAL ANALYSIS: Independent 'T-test' was used for comparing mean ± SD values. RESULTS: Statistically significant improvements in both plaque and gingival bleeding indices were obtained on follow-up observations at 3rd and 6th months. CONCLUSION: The use of specialized tactile and audio tools significantly improved the oral health status of visually impaired school children.
ABSTRACT
The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.
ABSTRACT
In traumatic dental injuries in children, due to a lack of maturity to cope with the situation, pain intolerance, amount of treatment procedure, and parental anxiety, simplified and non-invasive treatment procedures, such as biologic restorations, are useful. Using advanced adhesive material for fragment reattachment provides excellent esthetic results and a positive attitude from the patient and family. The purpose of this case report is to describe the biological restoration of a complicated crown-root fracture of a primary maxillary central incisor with the fragment reattachment technique.
Subject(s)
Dental Restoration, Permanent , Incisor , Tooth Crown , Tooth Fractures , Tooth Root , Tooth, Deciduous , Humans , Male , Composite Resins , Dental Bonding/methods , Dental Restoration, Permanent/methods , Incisor/injuries , Maxilla , Resin Cements , Tooth Crown/injuries , Tooth Fractures/therapy , Tooth Fractures/complications , Tooth Root/injuries , Tooth, Deciduous/injuries , Child, PreschoolABSTRACT
Objectives: A significant gap is observed between the proportion of individuals suffering from mental health (MH)-related conditions and those receiving adequate MH care services, especially in rural areas. This study highlights and contextualizes MH concerns and its extant knowledge as well as gender roles in rural Maharashtra (India). Methods: Using in-depth interviews, MH themes were highlighted analytically among 72 female beneficiaries of Svatantra from the six administrative divisions (Konkan, Nashik, Pune, Aurangabad, Amravati and Nagpur) in the state of Maharashtra, India. Results: The notion that MH concerns exist among women from rural communities was well supported. Along with MH concerns, the participants reported somatic concerns in the context of adverse life experiences. Furthermore, systemic issues such as financial problems, familial concerns, presence of addictions and pressures of gender role-related responsibilities were significant triggers for MH problems. Conclusions: Overall, this study aimed at improving the understanding of the MH needs of women in rural Maharashtra, which can further catalyze an exploration of their general MH and devise suitable interventions for the same.
ABSTRACT
BACKGROUND: Bortezomib, a commonly used anti-myeloma drug, is metabolized by liver microsomal enzymes which may be polymorphic and responsible for lack of response in 30% patients. Hence, the association of CYP2C19 polymorphism with treatment response was explored in this study. METHODS: Treatment naive multiple myeloma (MM) patients, eligible for bortezomib-based induction treatment, were recruited as per the inclusion - exclusion criteria. The genotyping of CYP2C19 was done using polymerase chain reaction-restriction fragment length polymorphism for *2, *3 and *17 alleles. The incidence and severity of peripheral neuropathy were noted at follow-up visits and graded as per CTCAE criteria ver 5.0. RESULTS: Total 220 patients were recruited from August 2016 till May 2021; with a mean age of 55.6 (9.5) years and 65.9% males. Bortezomib+cyclophosphamide+dexamethasone (41.8%) and bortezomib+lenalidomide+dexamethasone (38.2%) were the most prescribed regimens. The CYP2C19 was polymorphic in 38.6%, 2.3% and 23.7% patients for *2, *3 and *17 allele respectively. There were 195 treatment responders and 25 non-responders, and CYP2C19*2 allele was different between responders and non-responders (p = 0.02). All extensive metabolisers (n = 54) were noted to be treatment responders. Peripheral neuropathy was reported by 23.2% patients. The frequency of peripheral neuropathy was somewhat lower in patients having either *2/*2 or *3/*3 allele pattern for CYP2C19 (p = 0.44). CONCLUSIONS: Polymorphism in CYP2C19 enzyme is likely to have an impact on bortezomib treatment response and peripheral neuropathy. The study suggests the role of pharmacogenetics in personalised treatment of MM.
Subject(s)
Bortezomib , Cytochrome P-450 CYP2C19 , Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Bortezomib/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Female , Male , Middle Aged , Aged , Polymorphism, Genetic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Antineoplastic Agents/therapeutic use , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/drug therapy , Treatment Outcome , GenotypeABSTRACT
OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.
Subject(s)
Hypoglycemic Agents , India , Humans , Retrospective Studies , Hypoglycemic Agents/economics , Hypoglycemic Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/economics , Drugs, Generic/economics , Drugs, Generic/therapeutic use , Hypolipidemic Agents/economics , Hypolipidemic Agents/therapeutic use , Heart Disease Risk Factors , Drug Costs , Hypertension/drug therapy , Hypertension/economics , Diabetes Mellitus/drug therapy , Diabetes Mellitus/economics , Dyslipidemias/drug therapy , Dyslipidemias/economics , Antihypertensive Agents/economics , Antihypertensive Agents/therapeutic use , Costs and Cost AnalysisABSTRACT
INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.
Subject(s)
Carcinoma, Renal Cell , Hand-Foot Syndrome , Kidney Neoplasms , Sunitinib , Urea , Vascular Endothelial Growth Factor Receptor-2 , Humans , Sunitinib/administration & dosage , Sunitinib/pharmacokinetics , Sunitinib/adverse effects , Double-Blind Method , Carcinoma, Renal Cell/drug therapy , Male , Female , Middle Aged , Urea/analogs & derivatives , Urea/pharmacokinetics , Urea/administration & dosage , Kidney Neoplasms/drug therapy , Hand-Foot Syndrome/etiology , Hand-Foot Syndrome/prevention & control , Vascular Endothelial Growth Factor Receptor-2/genetics , Pilot Projects , Aged , Polymorphism, Single Nucleotide , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Quality of Life , Treatment Outcome , Administration, Topical , Adult , Indoles/administration & dosage , Indoles/pharmacokinetics , Indoles/adverse effectsABSTRACT
BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Prescriptions , Humans , Cross-Sectional Studies , Tertiary Care Centers , India/epidemiology , Anti-Bacterial Agents/adverse effects , Drug PrescriptionsABSTRACT
Sustaining an inhalation injury increases the risk of severe complications and mortality. Current evidential support to guide treatment of the injury or subsequent complications is lacking, as studies either exclude inhalation injury or design limit inferences that can be made. Conventional ventilator modes are most commonly used, but there is no consensus on optimal strategies. Settings should be customized to patient tolerance and response. Data for pharmacotherapy adjunctive treatments are limited.
Subject(s)
Burns , Respiratory Insufficiency , Humans , Ventilators, Mechanical , Consensus , Critical Care , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapyABSTRACT
Rationale: Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications. Aim: The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD. Sample size: Using 80% power and an alpha error of 5 %, presuming a 10%-15% drop-out rate, a total of 2200 patients will be recruited for the study. Methodology: This is a prospective, randomised, double-blind, placebo controlled trial. Study outcomes: The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase. Discussion: The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.
ABSTRACT
BACKGROUND: Small round cell tumors (SRCTs) are a group of malignant neoplasms with minimal or no differentiation, characterized by the presence of round cells with high nuclear-cytoplasmic ratio. Although SRCTs can occur in any part of the body, involvement of central nervous system (CNS) is uncommon. AIM: We aimed to study the clinicopathological spectrum of cranial SRCT diagnosed in our institute over a period of four years (2016-2019). MATERIAL AND METHODS: A retrospective review of medical records (2016-2019) with a morphological diagnosis of cranial SRCT was made. Both intra-axial and extra-axial tumors were included. A total of 60 cases were retrieved, and the clinical and histopathological features were studied. Special cytochemical staining and immunohistochemistry were performed, where needed. RESULTS: The mean age at presentation was 18.4 years (range, 1-60 years), with a male-to-female ratio of 2.5:1. The most common site was posterior fossa of brain (n = 28, 47%), followed by dorso-lumbar spine (n = 9, 15%). The most common type of tumor was medulloblastoma (n = 29, 48.3%), followed by Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) (n = 11, 18.3%), non-Hodgkin lymphoma (NHL) (n = 9, 15%), neuroblastoma (n = 3, 5%), and CNS embryonal tumor, NOS (n = 2, 3.3%). One case each of atypical teratoid rhabdoid tumor (ATRT), rhabdomyosarcoma, pineoblastoma, melanoma, rhabdomyosarcoma, and undifferentiated pleomorphic sarcoma was also documented. CONCLUSIONS: SRCTs have a variable age of presentation. Their incidence in CNS is low as compared to other organ systems. On light microscopy, the histopathology of these lesions is overlapping, posing a great diagnostic dilemma for the pathologist. The use of ancillary techniques like immunohistochemistry helps in arriving at the correct diagnosis. Treatment strategy and tumor prognosis also vary along the entire spectrum of SRCT, thus making exact characterization essential for proper management.
Subject(s)
Central Nervous System Neoplasms , Cerebellar Neoplasms , Neoplasms, Germ Cell and Embryonal , Neuroectodermal Tumors, Primitive , Rhabdomyosarcoma , Sarcoma , Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Tertiary Care Centers , Sarcoma/pathology , Rhabdomyosarcoma/pathology , Neuroectodermal Tumors, Primitive/pathology , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/epidemiologyABSTRACT
Due to multifactorial aetiology, tooth surfaces of primary dentition are more prone to dental caries and follow the specific pattern of dental caries which is difficult to control. The proper knowledge of caries-susceptible areas on individual primary teeth surfaces guides the clinician to take early preventive measures to stop the progression of dental caries. This study aims to find the prevalence of caries-susceptible areas on primary teeth surfaces in preschool children and the most commonly affected primary teeth. The study design adopted was a cross-sectional study. A total number of 3720 teeth of 186 preschool children were examined for initial pinpoint caries lesions using World Health Organization (WHO) caries detection criteria. 33 caries-susceptible areas were examined on individual primary tooth surfaces of preschool children who visited the Faculty of Dental Sciences. Each tooth surface was recorded separately and no radiographic examination was done. Obtained data was analysed keeping the level of significance at 5%. The overall prevalence of caries-susceptible area was found significantly higher in the maxillary teeth (Maxillary teeth: 41.7% vs. Mandible teeth: 30.7%; p < 0.001) and anterior teeth (Anterior teeth: 43.7% vs. Posterior teeth: 28.4%; p < 0.001). The prevalence of caries-susceptible area on primary teeth on the right side when compared to left counterparts was similar (Right side-38.6% and left side-38.4%; p = 0.931). Area 2 was the most prevalent area on primary teeth surfaces and primary canine was more prevalent in caries-susceptible areas.
Subject(s)
Dental Caries , Child, Preschool , Humans , Dental Caries/prevention & control , Prevalence , Dental Caries Susceptibility , Cross-Sectional Studies , Tooth, DeciduousABSTRACT
A significant portion of the world's population suffers from blindness. Despite being a vital part of systemic health, oral health is neglected in such a population. The present study aimed to determine the oral health status of blind individuals in north India and to identify the factors affecting it. Sixty-nine blind students from a local school for the visually impaired were included in the study. A questionnaire was used to record the basic demographic details and oral habits, followed by an oral examination by a single trained dentist to record dental caries, periodontal status and dental trauma. The prevalence of Dental caries was 63.8% (mean 1.43 ± 1.61). Gingival bleeding on probing (BOP) was found in 60.9% of individuals. Dental trauma prevalence was 23.2%, and harmful oral habits were found in 31.9% of individuals. Individuals experiencing a toothache in the last year had a 1.784 times higher risk of dental caries than those who didn't experience a toothache. Individuals having acquired blindness are 2.411 times more prone to dental trauma in comparison to those suffering from congenital blindness. Blind individuals have poor oral health. Toothache in the last one year is an important risk factor for dental caries in such individuals. Acquired blindness makes a person more susceptible to dental trauma than congenital blindness.
Subject(s)
Dental Caries , Oral Health , Humans , Dental Caries/epidemiology , Toothache , Blindness/epidemiology , Blindness/etiology , Socioeconomic FactorsABSTRACT
Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR-T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%-70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T-cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR-T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR-T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.