A Correlation of Tumour Budding and Tumour-Stroma Ratio with Clinicopathological Factors in Oral Squamous Cell Carcinoma.

Objectives: This study aimed to analyse the association of tumour budding (TB) and tumour-stroma ratio (TSR) with clinicopathological parameters that can be easily viewed on routine haematoxylin and eosin (H&E)-stained slides to provide an easy and cost-effective method for prognosticating oral squamous cell carcinoma (OSCC). Methods: This study was conducted at the ESIC Medical College and Hospital in Faridabad, India, from July 2022 to October 2022. In patients with histologically diagnosed OSCC, TB and TSR were evaluated via routine H&E-stained sections and correlated with clinicopathological parameters. Statistical analysis was performed using Chi-squared test. Results: A total of 50 patients were included. The mean age of participants was 61 ± 12.72, and the male-to-female ratio was 7.1:1. Most of the tumours were located on the tongue (46%), followed by the buccal mucosa (26%), gingivobuccal sulcus (12%) and retromolar trigone (8%). The palate and alveolus were the other sites involved, constituting 4% each. TB and TSR were both found to be significantly associated with the tumour grade, lymph node metastasis and tumour size. A highly significant correlation was also found between TB and TSR (P = 0.001). Conclusions: Both TB and TSR can be easily evaluated on routine H&E sections; they are highly reproducible and were found to be reliable independent prognostic markers in OSCC. Therefore, this simple and cost-effective method of prognostication, which is currently lacking in clinical practice, will help clinicians to identify patients with poor prognosis and thus individualise their treatment plan.

Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.

The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, n = 112) and healthy HA sojourners (n = 111). The present study investigated cfDNA characteristics such as concentration, fragment length size, degree of integrity, and subfractions reflecting mitochondrial-cfDNA copies in the two groups. The total cfDNA level was significantly higher in patients with HAPE, and the level increased with increasing HAPE severity (P = 0.0036). A lower degree of cfDNA integrity of 0.346 in patients with HAPE (P = 0.001) indicated the prevalence of shorter cfDNA fragments in circulation in patients compared with the healthy HA sojourners. A significant correlation of cfDNA characteristics with the peripheral oxygen saturation levels in the patient group demonstrated the translational relevance of cfDNA molecules. The correlation was further supported by multivariate logistic regression and receiver operating characteristic curve. To our knowledge, our study is the first to highlight the association of higher cfDNA concentration, a lower degree of cfDNA integrity, and increased mitochondrial-derived cfDNA population with HAPE disease severity. Further deep profiling of cfDNA fragments, which preserves cell-type specific genetic and epigenetic features, can provide dynamic physiological responses to hypoxia.NEW & NOTEWORTHY This study observed altered cell-free (cf) DNA fragment patterns in patients with high-altitude pulmonary edema and the significant correlation of these patterns with peripheral oxygen saturation levels. This suggests deep profiling of cfDNA fragments in the future may identify genetic and epigenetic mechanisms underlying physiological and pathophysiological responses to hypoxia.

Congenital Unilateral Hypoplasia of Kidney with Mesonephric Remnants in the Ureter: A Case Report.

Mesonephric remnants persist as an appendix of epididymis and paradidymis in efferent ductules in males and skene's glands and Gartner's ducts in females. The mesonephric remnant in the renal parenchyma is extremely rare and only a few cases have been reported in the literature. We present a case with a non-functioning atrophic left kidney. Histopathology showed variable-sized ducts filled with colloid-like material surrounded by collagenized stroma. The ureter showed hypertrophied muscle and a few ducts lined by flattened and a few by columnar epithelium resembling epididymis suggestive of mesonephric remnants. IHC for CD10, PAX 8, and GATA3 was positive. A diagnosis of congenital unilateral hypoplasia of kidneys and ureter with mesonephric remnants was given.

A critical appraisal of mucormycosis in COVID- 19 patients in a tertiary care centre in India.

Background and Purpose: Morbidity and mortality of opportunistic fungal infections in COVID-19 patients are less studied and defined. The patients receiving immunosuppressive therapy, broad-spectrum antibiotics, corticosteroids, and invasive and non-invasive ventilation are the high-risk groups. Materials and Methods: The demographic profile as well as clinical and radiological findings of all the patients with COVID-19 suspected of Mucormycosis (MM) were recorded. The tissue samples from all the patients were sent for microbiological (KOH mount and culture) and histopathological analysis for confirmation of MM. Results: In total, 45 COVID-19 patients suspected of MM were included in the study and MM was confirmed in 42 patients. The mean age of the patients was 50.30±14.17 years with a female: male ratio of 1.1:1. The most common symptom was headache (52.38%) followed by purulent nasal discharge (38.09%) and facial pain in 33.33% of the cases. The ocular symptoms included a diminution of vision (33.33%) and redness of the eye (2.38%). The most common site of involvement was rhino-orbital (42.85%) followed by sinonasal (23.80%) and rhino cerebral (19.04%). Majority (38.09%) of the patients were diagnosed with stage II of Rhino-orbital-cerebral Mucormycosis (ROCM) based on radiology. A history of diabetes mellitus and steroids was present in 97.61% and 85.71% of the cases, respectively. Moreover, KOH was positive for MM in 97.61% of the cases while the culture was positive in only 35.71% of the cases. In addition, on histopathology, MM was confirmed in 64.28 % of the cases. Mixed growth with Aspergillus species and Rhizopus species was observed in 14.28% of the cases in culture and 11.90% of the cases in histopathology test. Furthermore, angioinvasion was found in 23.80% of the cases according to the histopathology test. Conclusion: Based on the results, the most common conditions associated with MM in COVID-19 patients were diabetes mellitus and steroid therapy. A high level of clinical suspicion aided with diagnostic tests, including KOH mount, culture, histopathology, and radiology which helped the early detection of opportunistic fungal infection in COVID-19 patients to ensure timely treatment.

Association of transient mitochondrial functional impairment with acute heat exposure in children from Muzaffarpur region of Bihar, India.

Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated as potential sources of the ailment. However, no conclusive etiology for AES has been identified in the affected children. During recent rounds of the outbreak, metabolic abnormalities have been documented in these children, and a direct correlation was observed between higher environmental temperature during the peak-summer month and AES caseload. The clinical and metabolic profiles of these children suggested the possible involvement of mitochondrial dysfunction during heat stress as one of the several contributory factors leading to multisystem metabolic derangement. The present study observed that mitochondrial function parameters such as cell death, mitochondrial membrane potential, oxidative stress, and mitochondrial pathway-related gene expression in peripheral blood mononuclear cells (PBMCs) isolated from children were affected in peak-summer when compared to post-summer months. Similar observations of mitochondrial function parameters along with impaired bioenergetic parameters were demonstrated in the heat-exposed model of PBMCs isolated from healthy adult individuals. In conclusion, the results suggested that there is an association of transient mitochondrial dysfunction when exposed to sustained heat during the summer months. One may consider mitochondrial dysfunction as one of the important factors leading to an outbreak of AES among the children from affected regions though this needs to be substantiated with further studies.

Synchronous Occurrence of Adult Granulosa Cell Tumor with Fibroma in One Ovary and Brenner Tumor in Other Ovary: An Extremely Unusual Case.

Ovarian tumors are a common form of neoplasia in women and it accounts for about 30% of female genital cancers. A coexistence of ovarian tumors with the same histogenetic origin such as germ cell or epithelial or sex cord stromal, but different histologic subtype is relatively common, whereas a synchronous occurrence of tumors with different histogenetic origin is rare. We report a case of 58-year-old woman with the synchronous presentation of adult granulosa cell tumor with fibroma (ovarian tumors with the same origin (sex cord stromal) but different histologic type) in one ovary and Brenner tumor (epithelial origin) in other ovary. Our patient presented with postmenopausal bleeding and was diagnosed with this rare combination of ovarian tumors on histopathology supplemented with immunohistochemistry. On extensive literary search, there is only a single report of mixed ovarian tumor composed of Brenner tumor and adult-type granulosa cell tumor. Our case is different from the above-mentioned report as although, in our patient both tumors coexisted, but in contralateral ovaries.

Xanthogranulomatous Change in a Leiomyoma: First Report of an Extremely Rare Variant/Degenerative Change.

Xanthogranulomatous inflammation, a specific form of chronic inflammation, is marked by parenchymal destruction, proliferative fibrosis, and infiltration of typical foamy histiocytes admixed with hemosiderin-laden macrophages and foreign-body giant cells. Myometrial xanthomatosis, a term designated for nodular or diffuse histiocytic hyperplasia of the myometrium, has been reported in association with pregnancy-related procedures. Moreover, a 2-3-fold increase in histiocytic counts has been observed in leiomyomatous areas than in adjacent normal myometrium. The first evidence of collections of lipid-laden macrophages was documented in the form of yellowish degeneration of uterine leiomyomas. We report a case of xanthogranulomatous change in a leiomyoma in a 47-year-old female who presented with abnormal uterine bleeding. To the best of our knowledge, this is the first report of xanthogranulomatous variant/degenerative change in a leiomyoma. This case highlights a new variant of leiomyoma which both gynecologists and pathologists should be aware of as it may pose a diagnostic challenge both clinically as well as pathologically.

Evaluation of the Effects of Topical Fluoride Varnish and Fluoride Releasing Adhesive on Shear Bond Strength of Orthodontic Brackets: An In Vitro Study.

Aim: The aim of this study was to evaluate the in vitro effects of topical fluoride varnish and fluoride-releasing adhesive on the shear bond strength (SBS) of orthodontic brackets. Materials and methods: A total of 60 extracted premolars were bonded to 0.022, stainless steel brackets and equally divided into three groups (n = 20) based on the adhesive used-Group I- Transbond XT Plus color change (3M Unitek), Group II- Transbond XT followed by application of fluoride varnish, and Group III- Transbond XT (3M Unitek) adhesive and their bond strengths were compared. Brackets were debonded with a universal testing machine. The modified adhesive remnant index (ARI) was also recorded. Data were analyzed by using an analysis of variance, and a post hoc test was performed for multiple comparisons among the groups. Results: There were no significant differences between the SBSs (p = 0.91) between the groups. Also, no significant difference was found in the modified ARI (p = 0.093). Conclusion: The orthodontic adhesives used in our study, with or without the application of topical fluoride varnish, did not have a significant effect on the bond strengths of brackets. Clinical significance: Adhesives evaluated in this study can be successfully used for bonding brackets. How to cite this article: Chauhan C, Mangla R, Gandhi G, et al. Evaluation of the Effects of Topical Fluoride Varnish and Fluoride Releasing Adhesive on Shear Bond Strength of Orthodontic Brackets: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(1):37-41.

Biochemical and molecular mechanisms of antibiotic resistance in Salmonella spp.

Salmonella is a diverse Gram-negative bacterium that represents the major disease burden worldwide. According to WHO, Salmonella is one of the fourth global causes of diarrhoeal disease. Antibiotic resistance is a worldwide health concern, and Salmonella spp. is one of the microorganisms that can evade the toxicity of antimicrobials via antibiotic resistance. This review aims to deliver in-depth knowledge of the molecular mechanisms and the underlying biochemical alterations perceived in antibiotic resistance in Salmonella. This information will help understand and mitigate the impact of antibiotic-resistant bacteria on humans and contribute to the state-of-the-art research developing newer and more potent antibiotics.

Sclerosing angiomatoid nodular transformation of spleen: A rare case report.

ABSTRACT: Sclerosing angiomatoid nodular transformation (SANT) is a reactive non-neoplastic, rare vascular lesion of the spleen. The histology shows multiple angiomatoid nodules surrounded by proliferative stroma. A 31-year-old lady presented with an abdominal mass for 6 months. Contrast-enhanced computed tomography (CECT) abdomen was suggestive of hemangiopericytoma/hemangioendothelioma. An open splenectomy was performed, and the resected specimen was sent for histopathology examination. The gross examination showed a bosselated mass present at the lower pole of the spleen measuring 8 × 8 cm with peripherally located coalescing red-brown nodules embedded in a dense fibrous stroma on the cut surface. On microscopy, multiple circumscribed angiomatoid nodules comprising irregular slit-like vascular channels lined by plump endothelial cells were seen embedded in dense sclerotic stroma. Because of the lack of specific diagnostic features, it is difficult to diagnose SANT clinically and radiologically. However, the typical histopathological findings are a clue in clinching the diagnosis.

Heterologous expression of hAID in E. coli leads to the production of a splice isoform of AID: hAIDδC, a mystery to be explored.

Activation-induced cytidine deaminase (AID) is a key player that initiates antibody diversification in activated B-cell. AID mediates somatic hypermutation (SHM) and class switch recombination (CSR) via the deamination of cytosine to uracil at the Ig locus, resulting in the production of high-affinity antibodies. AID is predominantly restricted to Ig genes, whereas off-targeting of AID leads to lymphocyte-related malignancies. Interestingly, apart from FL-AID other splice isoforms of AID are highly expressed in the lymphocyte malignancies. In our study, we found that the heterologous expression of hAID-FL in E. coli cells produced two induced bands of hAID as demonstrated by SDS-PAGE and western blotting. Remarkably, peptide mapping data predicted that one band is hAID-FL and the other is its splice isoform, hAIDδE4a. To get an insight into why E. coli cells expressed hAID-FL and hAID variant, we mutated the 5' and 3' splice site of a putative intron of hAID, but it failed to produce only hAID-FL. Incidentally, hAID expressed with fusion partners also displayed two bands, and peptide mapping data strongly suggest that besides hAID-FL, the lower band showed a significant number of amino acids missing towards the C-terminal domain (named as hAIDδC). Our results are the first report to show that expression of recombinant hAID alone or irrespective of solubilization tags in E. coli cells produced hAID-FL and hAIDδC. It will be fascinating to explore the potential mechanism underlying the expression of hAIDδC from recombinant hAID plasmid in E. coli cells.

Clinical and Genetic Profile of Children With Short Stature Presenting to a Genetic Clinic in Northern India.

OBJECTIVE: To define the spectrum of genetic disorders in patients with short stature visiting the genetic out-patient department in a tertiary care hospital. METHODS: A chart review was done for 455 individuals (10 months-16 yrs) with short stature, who were evaluated at the genetic clinic from 1 January, 2017 upto 31 October, 2018. 226 patients who needed detailed evaluation, the spectrum of genetic diagnosis is presented. RESULTS: Proportionate short stature was identified in 63% individuals (n=142) of which 93 (65%) were recognizable syndromes such as Turner syndrome, and William syndrome, and RASopathies. In clinically undefined syndromes (39, 27%), a diagnosis could be made by karyotype (n=3/10), chromosomal microarray (6/12) and exome sequencing (1/6). In the 84 children in the disproportionate short stature group (37%), lysosomal storage disorders (LSDs) (45%, n=38) were identified by enzyme analysis in 86.8% and skeletal dysplasias (44%, n=37) identified by skeletal survey in 89% cases. CONCLUSIONS: In undefined syndromic short stature, chromosomal microarray may be the first investigation of choice if phenotyping is not suggestive of a specific genetic syndrome. Exome sequencing can be useful in identifying newer genes among idiopathic and familial short stature cohorts.

Combined effects of biochar and fertilizer applications on yield: A review and meta-analysis.

The use of biochar is changing, and the combined application of biochar with fertilizer is increasingly gaining acceptance. However, the yield gains results reported in the existing literature through the co-application of fertilizer with biochar are conflicting. To resolve this, we utilized a meta-analysis of 627 paired data points extracted from 57 published articles to assess the performance of the co-application of biochar and fertilizers on crop yield compared with the corresponding controls. We also studied the impact of biochar characteristics, experimental conditions, and soil properties on crop yield. Our analysis showed that individually, biochar and inorganic fertilizer increased crop yield by 25.3% ± 3.2 (Bootstrap CI 95%) and 21.9% ± 4.4, respectively. The co-application of biochar with both inorganic and organic fertilizers increased crop yield by 179.6% ± 18.7, however, this data needs to be treated with caution due to the limited dataset. The highest yield increase was observed with amendments to very acidic soils (pH ≤5), but the benefits of biochar were not affected by the rate and the time after the application. In addition, the effects of biochar are enhanced when it is produced at 401-500 °C with a C:N ratio of 31-100. Our results suggest that the co-application of biochar with either inorganic and/or organic fertilizers in acidic soils increase crop productivity compared to amendment with either fertilizer or biochar. Our meta-analysis supports the utilization of biochar to enhance the efficiency and profitability of fertilizers.

The effect and correlation of smoking with platelet indices, neutrophil lymphocyte ratio and platelet lymphocyte ratio

ABSTRACT Introduction: Smoking is associated with the occurrence and progression of cardiovascular diseases, inflammatory disorders and malignancies. Objective: To study the platelet indices, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in smokers and their correlation with smoking pack-years. Method: A total of 110 smokers and 110 non-smokers were included. The smokers were grouped into three groups: mild (<5 pack-years), moderate (5-10 pack-years) and heavy (>10 pack-years). The platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were noted. The NLR and PLR were calculated and the statistical analysis was made using the Student's T-test, Analysis of Variance (ANOVA) and Spearman's correlation coefficient. Results: The platelet count, PCT and PDW were significantly higher with mean values: 218.56 ± 121.31 vs 203.23 ± 80.35 (p-value = 0.038), 0.27 ± 0.10 vs 0.26 ± 0.10 (p-value = 0.041) and 12.54 ± 1.45 vs 11.99 ± 1.70 (p-value = 0.001) in smokers and non-smokers, respectively. The PLR differed significantly with mean values: 119.40 ± 84.81 in smokers and 181.99 ± 313.09 in non-smokers, with a p-value of 0.045. A significant positive correlation was found between pack-years of smoking and platelet count and PLR with the Pearson correlation coefficient of 0.250 and 0.198 and p-values, 0.008 and 0.037, respectively. The Platelet Count, PCT, MPV and PDW varied significantly between mild, moderate and heavy smoker groups, with p-values of 0.045, 0.010, 0.015 and 0.017, respectively. Conclusion: The platelet indices and inflammatory markers NLR and PLR are derived from routine blood investigations, which are easily available and inexpensive. The monitoring of platelet indices, along with the PLR, can be used as early predictors of morbidity in smokers.

The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer.

Prostate cancer is the second most frequently occurring cancer diagnosed among males. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation. In this review, we focused on studies that demonstrated anticancer effects of cannabinoids and their possible mechanisms of action in prostate cancer. Besides the palliative effects of cannabinoids, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of cancers. This analysis may provide pharmacological insights into the selection of specific cannabinoids for the development of antitumor drugs for the treatment of prostate cancer.

Association of Hematologic biomarkers and their combinations with disease severity and mortality in COVID-19- an Indian perspective.

BACKGROUND: COVID-19 is a systemic viral infection with a significant impact on the hematopoietic system, hemostasis as well as immune system. It would be of utmost importance to explore if the most routinely used tests could serve as an aid in determining patient's clinical status or predicting severity of the disease. METHODS: A prospective cross-sectional study was conducted on 506 Covid-19 positive patients and 200 controls over a period of two months (June and July 2020). The cases were sub-classified based on disease severity into mild to moderate (n=337), severe (n=118) and very severe (n=51) and based on survivor status into survivors (n=473) and non-survivors (n=33). RESULTS: There were statistically significant differences in WBC count, Absolute neutrophil count (ANC), Absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) Red blood cell distribution width (RDW-SD) and RDW CV between covid cases vs controls; among the clinical subgroups and among the survivors and non-survivors. There was a significant strong positive correlation between various parameters, that is, NLR and MLR (r: 0.852, P=0), MPV and PDW (r: 0.912, P=0), MPV and PLCR (r: 0.956, P=0), PDW and PLCR (r: 0.893, P=0). NLR (AUC: 0.676, P=0) was the best single parameter and NLR+RDW-CV was best combination parameter as per area under curve (0.871) of ROC to distinguish severe from mild to moderate disease. CONCLUSIONS: Leucocytosis, neutrophilia, lymphopenia and monocytosis were characteristic findings in covid cases while NLR and NLR+RDW-CV emerged as the most effective single and combination CBC parameters in distinguishing mild to moderate and severe cases respectively.

Effects of biochar, compost, and biochar-compost on soil total nitrogen and available phosphorus concentrations in a corn field in Papua New Guinea.

Replenishing soil nutrient particularly total nitrogen (TN) and available phosphorus (P) is important to sustain soil health for food production. Organic amendments such as compost and biochar are commonly applied to improve soil nutrient retention especially N and P. In farms, biochar is usually applied once followed by applying other organic amendment applied in their full rates. Both form and rate of organic amendments can affect soil nutrient concentrations particularly in short term. This study aimed to examine the effects of compost and mixture of compost with biochar (both at full rates) on soil nutrient concentrations in short term. A randomised complete block filed experiment with eight replicates was used for this study. The effects of biochar (5 t/ha) only, compost (at the rates of 10 t/ha, 25 t/ha and 35 t/ha) and biochar mixed with compost (5 t/ha and 10 t/ha, respectively) on soil nutrient concentrations compared with control were explored in a corn field. Compost treatment at the rate of 35 t/ha had significantly higher TN, available P, calcium (Ca) and iron (Fe) compared with other treatments and control. Soil potassium (K) levels remained unchanged among all treatments. Biochar only treatment had significantly higher available P and Ca concentrations compared with biochar mixed with compost treatment. Compost application at higher rate (35 t/ha) proved best practice to significantly increase TN and available P concentrations in short term. Significantly higher available P concentration in biochar only treatment compared with the biochar mixed with compost treatment could have been associated with stimulation of P immobilisation when biochar was mixed with compost. Our results indicated that the form and rate of organic amendments in short term cropping systems are important to be considered while applying to a volcanic soil to ensure N and P availability for plants are not compromised.