Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.

AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.

Development and challenges in the discovery of 5-HT1A and 5-HT7 receptor ligands.

Serotonin (5-hydroxytryptamine) is a small molecule that acts both in the central and peripheral nervous system as a neurotransmitter and a hormone, respectively. Serotonin is synthesized via a multi-stage pathway beginning with l-tryptophan, which is converted by an enzyme called tryptophan hydroxylase into L-5-Hydroxytryptophan. It is well-known for its significance in the control of mood, anxiety, depression, and insomnia as well as in normal human functions such as sleep, sexual activity, and appetite. Thus, for medical chemists and pharmaceutical firms, serotonin is one of the most desirable targets. Among the seven different classes of serotonin receptors, the 5-HT1A was one of the first discovered serotonin receptors, and the 5-HT7 was the last addition to the serotonin receptor family. Both the classes were thoroughly examined. 5-HT1A neurotransmission-related dysfunctions are linked to many psychological conditions such as anxiety, depression, and movement disorders. 5-HT7 is a member of the cell surface receptor GPCR superfamily and is regulated by the serotonin neurotransmitter. It has been the focus of intensive research efforts since its discovery, which was prompted by its presence in functionally important regions of the brain. The thalamus and hypothalamus have the highest 5-HT7 receptor densities. They are also found in the hippocampus and cortex at higher densities. Thermoregulation, circadian rhythm, learning and memory, and sleep are all associated with the 5-HT7 receptor. It is also suspected that this receptor may be involved in the control of mood, indicating that it may be a beneficial target for depression treatment. Several differently structured molecules such as aminotetralins, ergolines, arylpiperazines, indolylalkylamines, aporphines, and aryloxyalkyl-amines are known to bind to 5-HT1A and 5-HT7 receptor sites. In brain serotonin receptors 5-HT1A and 5-HT7 are strongly co-expressed in regions involved in depression. However, their functional interaction has not been identified. An overview of the 5-HT1A and 5-HT7 receptor ligands belonging to different chemical groups is mentioned in this review.

Evaluation of advanced, pathophysiologic new targets for imaging of CNS.

The inadequate information about the in vivo pathological, physiological, and neurological impairments, as well as the absence of in vivo tools for assessing brain penetrance and the efficiency of newly designed drugs, has hampered the development of new techniques for the treatment for variety of new central nervous system (CNS) diseases. The searching sites such as Science Direct and PubMed were used to find out the numerous distinct tracers across 16 CNS targets including tau, synaptic vesicle glycoprotein, the adenosine 2A receptor, the phosphodiesterase enzyme PDE10A, and the purinoceptor, among others. Among the most encouraging are [18 F]FIMX for mGluR imaging, [11 C]Martinostat for Histone deacetylase, [18 F]MNI-444 for adenosine 2A imaging, [11 C]ER176 for translocator protein, and [18 F]MK-6240 for tau imaging. We also reviewed the findings for each tracer's features and potential for application in CNS pathophysiology and therapeutic evaluation investigations, including target specificity, binding efficacy, and pharmacokinetic factors. This review aims to present a current evaluation of modern positron emission tomography tracers for CNS targets, with a focus on recent advances for targets that have newly emerged for imaging in humans.

Calyceal diverticula: Clinical, radiological and histopathological findings of an uncommon entity with presumed congenital origin.

Calyceal diverticula (CD) are relatively uncommon urologic conditions that generally follow an asymptomatic course and rarely require medical intervention. CD are thought to have a congenital origin due to abnormalities during the process of ureteral bud formation. Clinically and radiologically, they can mimic multiple neoplastic and non-neoplastic renal processes, with potentially relevant differences in the management of these patients. Symptoms are usually associated with the presence of stones, obstruction to the drainage of the diverticulum, large size, or secondary infection. In chronic cases, surgery might become necessary, creating an opportunity to examine the histopathological characteristics of this condition. Although these are benign in the majority of patients, some rare instances of malignancy arising from the CD have been reported. In this series, we addressed the clinical, radiological, and histopathological findings of CD.

Modified benzoxazolone (ABO-AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein.

Acetamidobenzoxazolone (ABO) has been modified to ABO-AA, 2-(2-(5-bromo/chloro benzoxazolone)acetamide)-3-(1H-indol-3-yl)propionate to improve pharmacokinetics and lipophilicity (log p = 2.04). The final compound was synthesized in better yield and in fewer steps than previously reported MBIP-Br (70% vs. 62%). Computational docking confirmed binding of MBIP-Cl with translocator protein (TSPO) as well as with mutant TSPO (-8.99 for PDB: 4RYQ and -9.30 for PDB: 4UC1, respectively). Ex-vivo biodistribution and scintigraphy showed that 99m Tc-MBIP-Cl is better than 99m Tc-MBIP-Br in terms of uptake in TSPO-rich organs and release kinetics 0-120 min postinjection. At 15 min, uptake was 2.75-fold (12.91%ID/g vs. 4.69%ID/g) in lung and seven-fold (5.16%ID/g vs. 0.72%ID/g) in heart for 99m Tc-MBIP-Cl compared to that of 99m Tc-MBIP-Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.

Human health risk assessment and PAHs in a stretch of river Ganges near Kanpur.

The presence of 13 polycyclic aromatic hydrocarbons (PAHs) was measured in a small stretch of river Ganges in Kanpur, using high-performance liquid chromatography equipped with photodiode array detector (HPLC/PDA). Non-carcinogenic risk on human health was calculated in the form of hazardous index. Carcinogenic risk was calculated as chronic daily intake and incremental lifetime cancer risk (ILCR) with the help of monitored PAHs in river water. Due to non-availability of reference dose (RfD) values for all the 13 PAHs, the combined hazardous index for three PAHs was calculated. These values in winter, pre-monsoon, and post-monsoon period varied from 6.37 × 10-3 (Bithoor) to 1.12 × 10-2 (Jajmau), 2.89 × 10-3 (Bithoor) to 8.52 × 10-3 (Annandeshwar Temple), and 1.80 × 10-3 (Massacre Ghat) to 6.67 × 10-3 (Jajmau), respectively. In this study, the carcinogenic risk due to PAHs was calculated in the form of ILCR. ILCR due to benzo(a)pyrene (BaP) varied from 1.39 × 10-6 (Massacre Ghat) to 1.45 × 10-5 (Jajmau). ILCR was also calculated with the help of BaPeq for five age groups of people (adults, teenagers, children, toddlers, and infants). The outcome of the study indicates that there is a need to control pollution of the river water to maintain its quality. Continuous discharge of PAHs into the river poses both human health risk and ecological risk.

Isolation of pristine MXene from Nb4AlC3 MAX phase: a first-principles study.

Synthesis of pristine MXene sheets from MAX phase is one of the foremost challenges in getting a complete understanding of the properties of this new technologically important 2D-material. Efforts to exfoliate Nb4AlC3 MAX phase always lead to Nb4C3 MXene sheets, which are functionalized and have several Al atoms attached. Using the first-principles calculations, we perform an intensive study on the chemical transformation of MAX phase into MXene sheets by inserting HF, alkali atoms and LiF in Nb4AlC3 MAX phase. Calculated bond-dissociation energy (BDE) shows that the presence of HF in MAX phase always results in functionalized MXene, as the binding of H with MXene is quite strong while that with F is weak. Insertion of alkali atoms does not facilitate pristine MXene isolation due to the presence of chemical bonds of almost equal strength. In contrast, weak Li-MXene and strong Li-F bonding in Nb4AlC3 with LiF ensured strong anisotropy in BDE, which will result in the dissociation of the Li-MXene bond. Ab initio molecular dynamics calculations capture these features and show that at 500-650 K, the Li-MXene bond indeed breaks leaving a pristine MXene sheet behind. The approach and insights developed here for chemical exfoliation of layered materials bonded by chemical bonds instead of van der Waals can promote their experimental realization.

Box-Behnken design for optimum extraction of biogenetic chemicals from P. lanceolata with an energy audit (thermal × microwave × acoustic): a case study of HPTLC determination with additional specificity using on-line/off-line coupling with DAD/NIR/ESI-MS.

INTRODUCTION: The genus Pluchea comprises about 80 species distributed worldwide, out of them, only Pluchea lanceolata (DC.) Oliv. & Hiern, is used extensively in the traditional system of India. No chromatographic method is available for its quality. OBJECTIVES: To perform the energy audit for the extraction of biogenetic pentacyclic triterpene, its acetate and sterol from P. lanceolata utilising organic and four alternative solvents. Additionally to resolve the uncertainty of TLC determination, on-line/off-line coupling with a diode-array detector (DAD), and near-infrared (NIR) and electrospray ionisation (ESI) MS was introduced. METHODS: The extraction of taraxasterol (Tx), taraxasterol acetate (TxAc) and stigmasterol (St) from P. lanceolata was performed using three energy modes. The effects of different operating parameters were studied for optimum extraction yield using the design of experiments, that is, the central composite design and Box-Behnken design. In addition to the retention factor (Rf ) and visible spectral matching, two additional optical spectroscopic techniques, that is, NIR and ESI-MS, were applied for extended specificity. RESULTS: The method was developed for Tx, TxAc and St determination using HPTLC at 645 nm. The optimum extraction yield of targeted compounds was found to be higher with organic solvents than eco-friendly surfactants. The pulse ultrasonic assisted extraction (PUAE) has resulted in optimum extraction of compounds comparable to hot extraction. Both NIR and ESI-MS provided extended specificity in determination. CONCLUSION: The 5/1-PUAE was determined to be effective, reproducible, simple and energy efficient for the determination of Tx, TxAc and St in P. lanceolata. The offline coupling of NIR and ESI-MS with HPTLC led to considerable improvement in specificity.

Comparison of quantitative and qualitative anti-dsDNA assays.

OBJECTIVE: In evaluation of systemic lupus erythematosus (SLE), anti-double-stranded DNA antibodies (anti-dsDNA) play a significant role in diagnosis, monitoring SLE activity, and assessing prognosis. However, evaluations of the performance and limitations for recently developed methods for anti-dsDNA assessment are sparse. METHODS: Specimens used for antinuclear antibody testing (n = 129) were evaluated for anti-dsDNA assay comparability across 4 medical centers in the United States. The methods compared were Werfen Quanta Lite dsDNA, Zeus Scientific dsDNA Enzyme Immunoassay, Bio-Rad multiplex immunoassay (MIA) dsDNA, ImmunoConcepts Crithidia, and Bio-Rad Laboratories Crithidia. RESULTS: For quantitative anti-dsDNA measurements, Spearman's correlation coefficient was highest between Zeus and Werfen (ρ = 0.86; CI, 0.81-0.90; P < .0001). Comparison of MIA to Werfen or Zeus yielded similar results to each other (ρ = 0.58; CI, 0.44-0.68; P < .0001; and ρ = 0.59; CI, 0.46-0.69; P < .0001, respectively), but lower than the correlation between Zeus and Werfen. Positive concordance between assays ranged from 31.4% to 97.1%, and negative concordance between assays ranged from 58.5% to 100%. The detection of anti-dsDNA in those with SLE diagnosis ranged from 50.9% to 77.4% for quantitative assays and 15.1% to 24.5% for Crithidia assays. CONCLUSION: Current quantitative anti-dsDNA assays are not interchangeable for patient follow-up. Crithidia-based assays demonstrate high negative concordance and lack positive concordance among the methods.

Pancreatic Panniculitis: A Case Associated With Acute Pancreatic Allograft Rejection.

We present a unique case of pancreatic panniculitis (PP) in a 42-year-old male with a history of pancreas-after-kidney (PAK) transplant. The patient developed PP due to acute pancreas allograft rejection. Clinical manifestations included fevers, myalgias, arthralgias, and tender erythematous subcutaneous nodules on the lower extremities. A recent hospital admission was noted for acute pancreas allograft rejection related to low tacrolimus levels. Rheumatological and infectious disease workups were negative. Skin nodule punch biopsy confirmed PP with lobular panniculitis, necrotic adipocytes, basophilic debris, and calcification. Pancreatic biopsy showed evidence of parenchymal acute cellular rejection. Lipase and amylase levels were elevated (1781 U/L and 881 U/L, respectively). Treatment involved pulse solumedrol and thymoglobulin for pancreatic rejection, alongside adjustments to immunosuppressive medications. This case highlights the rarity of PP in a PAK recipient and its association with acute pancreas allograft rejection. Importantly, it is the first reported case of PP occurring solely in the context of pancreas transplant rejection, without concurrent kidney damage or rejection. Prompt diagnosis and management led to the resolution of skin and systemic symptoms. In conclusion, this report presents a clinically relevant and unique case of PP resulting from acute pancreas allograft rejection in a PAK transplant recipient. The findings underscore the importance of early diagnosis and management for positive patient outcomes, serving as a reminder to consider underlying pancreatic pathology when encountering PP in transplant recipients.

Supernumerary Nostril: A Rare Anomaly.

Supernumerary nostril or accessory nostril is a very rare congenital abnormality of nose. Less than 50 cases of same have been reported in English literature so far. In this study, the author present case of a 7-year-old female who had isolated supernumerary right nostril.

Comparative Evaluation of Maintenance of Cell Viability of an Experimental Transport Media "Ringer's Lactate" with Dextrose Normal Saline ORS Egg White and Infant Milk Formula for Transportation of an Avulsed Tooth.

Background and objective: The viability of the periodontal ligament (PDL) cells on the root surface of the avulsed tooth determines the prognosis of the replanted tooth, which in turn is determined by a suitable transport medium in which the tooth was stored. The aim of the present study is to evaluate and compare the effectiveness of Ringer's lactate (RL) as a storage medium for an avulsed tooth in maintaining the PDL cell viability with dextrose normal saline (DNS), oral rehydration salt (ORS), egg white (EW), and infant milk formula (IMF). Materials and methods: A total of 85 freshly extracted human teeth were divided into five experimental groups and two control groups. The positive and negative controls corresponded to 0-minute and 8-hour dry time, respectively. The experimental teeth were stored dry for 30 minutes and then immersed in one of five experimental media (RL, DNS, ORS, EW, and IMF) for 45 minutes. The teeth were then treated with collagenase type III and trypsin for 10 minutes. The number of viable PDL cells was counted with a hemocytometer and analyzed. Results: Statistical analysis showed that IMF, RL, and EW had no statistically significant differences among them in maintaining the viability of the PDL cells but were significantly better than DNS. No statistically significant difference between RL, EW, and ORS in the number of viable PDL cells. Conclusion: Infant milk formula (IMF), RL, and EW showed similar results within the parameters of the study; they can be used as alternative storage media for avulsed teeth. DNS showed poor results, and ORS could serve as short-term storage media if the other solutions are not readily available. Clinical significance: The search for an appropriate storage media with favorable pH and osmolality along with easy availability is the basic thought behind this study. How to cite this article: Kumar P, Kotumachagi SS, Fabi AJ, et al. Comparative Evaluation of Maintenance of Cell Viability of an Experimental Transport Media "Ringer's Lactate" with Dextrose Normal Saline ORS Egg White and Infant Milk Formula for Transportation of an Avulsed Tooth. Int J Clin Pediatr Dent 2023;16(3):453-458.

To Assess the Prevalence of Dental Caries and Its Association with Body Mass Index, Socioeconomic Status, Dietary Habits, and Oral Hygiene among 6-12-year-old Children in Faridabad.

Aim: The aim of our study was to assess the prevalence of dental caries and the body mass index (BMI) in included school-going children. Moreover, to examine the relationship between the prevalence of dental caries, BMI, and socioeconomic (SES) status and to evaluate sugar consumption and other dietary habits as risk factors for dental caries. Materials and methods: The present cross-sectional study was performed among 400 school-going children aged 6-12 years from Faridabad city, Haryana. Parents filled out questionnaires for their respective children. The clinical examination of dental caries was performed according to World Health Organization (WHO) 1997. The BMI calculation was done by measuring height and weight. Statistical analysis: The collected data were analyzed statistically using parametric and nonparametric tests. Results: The prevalence of dental caries in deciduous teeth was 95.5% and in permanent teeth was 47.3%, respectively. Conclusion: This study displayed the positive correlation of dental caries to BMI, oral hygiene practices, beverages, aerated drinks, chips, candy, and tea/coffee. Whereas the SES status and dietary habits Jam group variable had no significance in relation to dental caries. How to cite this article: Kapil D, Saraf BG, Sheoran N, et al. To Assess the Prevalence of Dental Caries and Its Association with Body Mass Index, Socioeconomic Status, Dietary Habits, and Oral Hygiene among 6-12-year-old Children in Faridabad. Int J Clin Pediatr Dent 2023;16(4):626-632.

Selective Reduction of CO2 on Ti2C(OH)2 MXene through Spontaneous Crossing of Transition States.

Direct reduction of gas-phase CO2 to renewable fuels and chemical feedstock without any external energy source or rare-metal catalyst is one of the foremost challenges. Here, using density functional theory and ab initio molecular dynamics (AIMD) simulations, we predict Ti2C(OH)2 MXene as an efficient electron-coupled proton donor exhibiting simultaneously high reactivity and selectivity for CO2 reduction reaction (CRR) by yielding valuable chemicals, formate, and formic acid. This is caused by CO2 spontaneously crossing the activation barrier involved in the formation of multiple intermediates. Metallic Ti2C(OH)2 contains easily donatable protons on the surface and high-energy electrons near the Fermi level that leads to its high reactivity. High selectivity arises from low activation barrier for CRR as predicted by proposed mechanistic interpretations. Furthermore, H vacancies generated during the product formation can be replenished by exposure to moisture, ensuring the uninterrupted formation of the products. Our study provides a single-step solution for CRR to valuable chemicals without necessitating the expensive electrochemical or low-efficiency photochemical cells and hence is of immense interest for recycling the carbon.

Reassessing the optimal volume for malignancy detection in serous fluid cytology.

BACKGROUND: The international system for reporting serous fluid cytopathology (TIS) recommends submitting at least 50-75 mL of serous fluid to decrease false-negative results. However, prior studies did not agree on specific volume requirements or consensus adequacy criteria. Our study aims to assess whether fluid volume affects the adequacy rate and to assess the minimum volume necessary for optimal adequacy in pleural and peritoneal fluids. METHODS: A total of 8530 serous fluid cytology cases were identified in the laboratory information system. Differences in mean fluid volume received in the laboratory were compared using an ANOVA Games-Howell test based on TIS category. The percentage of malignant diagnoses across the volume ranges of 0 to 5 mL, 5 to 10 mL, 10 to 25 mL, 25 to 50 mL, 50 to 75 mL, 75 to 100 mL, 100 to 150 mL, 150 to 250 mL, 250 to 500 mL, 500 to 2000 mL was compared in pleural and peritoneal fluids using a chi-square test, and a SiZer analysis was performed. RESULTS: Mean fluid volume in inadequate, atypical, and negative cases was significantly lower compared to positive cases. A SiZer analysis showed a positive relationship between the malignancy fraction of pleural and peritoneal fluids and fluid volume. The percentage of malignant diagnoses in pleural and peritoneal fluid samples increased significantly up to a volume range of 75-100 mL. CONCLUSIONS: There is a significant relationship between fluid volume, adequacy and detection of malignancy in serous effusion cytopathology. The malignancy fraction increases with larger fluid volumes but at least 75-100 mL of fluid should be submitted for optimal diagnosis of malignancy in pleural and peritoneal fluids.