Comparison of flow-mediated dilation (FMD) of the brachial artery in normotensive versus preeclamptic pregnant females.

Introduction: Flow-mediated dilation (FMD) of the brachial artery is an ultrasonography test that assesses the endothelial response to reactive hyperemia. The aim of this study was to assess the changes in FMD in preeclamptic pregnant patients and compare them with normotensive pregnant females. Methods: An analytical cross-sectional comparative study was conducted in the Department of Obstetrics and Gynaecology at King George's Medical University (KGMU) after obtaining ethical approval. A total of 110 normotensive and 100 preeclamptic patients were recruited for the study. Using a Toshiba Ultrasound Machine with a 7-12 MHz probe, the baseline diameter of the brachial artery D1 was measured. Afterward, the cuff of the sphygmomanometer was placed distally on the forearm and it was inflated up to ≥250 mm of Hg pressure and later slowly deflated. At 90th seconds after cuff deflation, the mean of three measurements of vessel caliber (D2) was obtained. The FMD% was obtained by the following equation: FMD (%) = [(D2 - D1)/D1] ×100, where D1 = basal diameter and D2 = post-occlusion diameter. All patients were followed till delivery for maternofetal outcome. Results: FMD% was significantly lower in the preeclampsia group, and it went on decreasing with increasing severity of preeclampsia. At the cutoff of 9.4 for FMD%, its sensitivity for the prediction of preeclampsia was 65.3%, specificity was 89.3%, positive predictive value (PPV) was 94%, and negative predictive value (NPV) was 50%. Discussion: FMD is a noninvasive test, and it gets decreased before clinical signs of preeclampsia, so it can be used as a predictor of preeclampsia.

Enantioselective Synthesis of ß-l-5-[(E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) Uracil)] (l-BHDU) via Chiral Pure l-Dioxolane.

ß-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU (17) has demonstrated excellent anti-VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP (24), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP (24) is needed. In this article, an efficient approach for the synthesis of l-BHDU (17) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU (17) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Superior haplotypes towards the development of blast and bacterial blight-resistant rice.

Rice blast and bacterial leaf blight, are major disease, significantly threatens rice yield in all rice growing regions under favorable conditions and identification of resistance genes and their superior haplotypes is a potential strategy for effectively managing and controlling this devastating disease. In this study, we conducted a genome-wide association study (GWAS) using a diverse set of 147 rice accessions for blast and bacterial blight diseases in replications. Results revealed 23 (9 for blast and 14 for BLB) significant marker-trait associations (MTAs) that corresponded to 107 and 210 candidate genes for blast and BLB, respectively. The haplo-pheno analysis of the candidate genes led to the identification of eight superior haplotypes for blast, with an average SES score ranging from 0.00 to 1.33, and five superior haplotypes for BLB, with scores ranging from 1.52cm to 4.86cm superior haplotypes. Among these, superior haplotypes LOC_OS12G39700-H4 and LOC_Os06g30440-H33 were identified with the lowest average blast scores of 0.00-0.67, and superior haplotype LOC_Os02g12660-H39 exhibited the lowest average lesion length (1.88 - 2.06cm) for BLB. A total of ten accessions for blast and eight accessions for BLB were identified carrying superior haplotypes were identified. These haplotypes belong to aus and indx subpopulations of five countries (Bangladesh, Brazil, India, Myanmar, and Pakistan). For BLB resistance, eight accessions from six countries (Bangladesh, China, India, Myanmar, Pakistan, and Sri Lanka) and four subpopulations (aus, ind1A, ind2, and ind3) were identified carrying superior haplotypes. Interestingly, four candidate genes, LOC_Os06g21040, LOC_Os04g23960, LOC_Os12g39700, and LOC_Os01g24640 encoding transposon and retrotransposon proteins were among those with superior haplotypes known to play a crucial role in plant defense responses. These identified superior haplotypes have the potential to be combined into a single genetic background through haplotype-based breeding for a broader resistance spectrum against blast and bacterial blight diseases.

Effect of vaginal douching with normal saline before insertion of dinoprostone vaginal insert for labor induction.

Objective: Vaginal pH has been suggested to be one of the causative factors, responsible for variation in prostaglandin efficacy for induction of labour. The purpose of this study was to analyse the effect of vaginal douching with normal saline before insertion of dinoprostone vaginal insert for induction of labour. Methods: This randomised controlled study was done in the Department of Obstetrics and Gynaecology for a period of 1 year. Using a computer-generated random number table, subjects were allocated in two groups. In group A (study group), vaginal douching was done with 20 cc of sterile 0.9% NaCl and vaginal pH was again measured with pH paper strips just before inserting dinoprostone pessary. Dinoprostone pessary was inserted without douching in group B (control group). Results: There was a significant increase in the vaginal pH after douching with normal saline (4.91 vs 5.52, P < 0.001). Mean intrinsic vaginal pH (pH before inserting dinoprostone insert) in women who delivered vaginally was significantly higher than that of the women who had a caesarean section (5.10 vs 4.63, P < 0.001). Time interval between dinoprostone insertion to active phase of labour, duration of active phase of labour, time interval between dinoprostone insertion, and complete cervical dilatation and mode of delivery were not significantly different between the two groups. Conclusion: Although douching with normal saline increases vaginal pH, douching does not help in increasing the chances of vaginal delivery because it gives a transient effect. Rather, it is intrinsic vaginal pH, which is a better decisive factor for successful vaginal delivery.

New insights into QTNs and potential candidate genes governing rice yield via a multi-model genome-wide association study.

BACKGROUND: Rice (Oryza sativa L.) is one of the globally important staple food crops, and yield-related traits are prerequisites for improved breeding efficiency in rice. Here, we used six different genome-wide association study (GWAS) models for 198 accessions, with 553,229 single nucleotide markers (SNPs) to identify the quantitative trait nucleotides (QTNs) and candidate genes (CGs) governing rice yield. RESULTS: Amongst the 73 different QTNs in total, 24 were co-localized with already reported QTLs or loci in previous mapping studies. We obtained fifteen significant QTNs, pathway analysis revealed 10 potential candidates within 100kb of these QTNs that are predicted to govern plant height, days to flowering, and plot yield in rice. Based on their superior allelic information in 20 elite and 6 inferior genotypes, we found a higher percentage of superior alleles in the elite genotypes in comparison to inferior genotypes. Further, we implemented expression analysis and enrichment analysis enabling the identification of 73 candidate genes and 25 homologues of Arabidopsis, 19 of which might regulate rice yield traits. Of these candidate genes, 40 CGs were found to be enriched in 60 GO terms of the studied traits for instance, positive regulator metabolic process (GO:0010929), intracellular part (GO:0031090), and nucleic acid binding (GO:0090079). Haplotype and phenotypic variation analysis confirmed that LOC_OS09G15770, LOC_OS02G36710 and LOC_OS02G17520 are key candidates associated with rice yield. CONCLUSIONS: Overall, we foresee that the QTNs, putative candidates elucidated in the study could summarize the polygenic regulatory networks controlling rice yield and be useful for breeding high-yielding varieties.

Bone marrow metastasis in nonhematological malignancies: A study from tertiary care center.

Introduction: Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis. Materials and Methods: This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis. Results: Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98). Conclusions: It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies.

Résumé Introduction: Le cancer métastatique présente un défi de traitement pour les cliniciens, en particulier pour les patients présentant une infiltration de moelle osseuse. Pour la stadification tumorale, la sélection du traitement et la stratification du risque de pronostic, l'état de la moelle osseuse doit être connu pour la présence ou l'absence de métastases. L'étude visait à évaluer les résultats hématologiques et l'analyse complète de la moelle osseuse dans les cas de tumeurs malignes non hématologiques avec métastases de la moelle osseuse. Matériel et méthodes: Cette étude rétrospective comprenait une récupération des archives ministérielles des 6 dernières années. Un total de patients atteints de tumeurs malignes non hématologiques ont été trouvés, dont 31,42% (104/331) présentaient des osmétastases médullaires. Une approche clinique intégrée avec les résultats de l'examen de la moelle osseuse et l'immunohistochimie chaque fois que nécessairea été utilisé pour établir un diagnostic définitif de métastases médullaires. Résultats: Dans la population étudiée, 31,42 % (104/331) des patients présentaient des tumeurs malignes non hématologiques qui se métastasaient à la moelle osseuse. La plupart des patients atteints de métastases de la moelle osseuse présentaient une anémie, qui a été trouvée dans 77,88% (81/104) des cas. Une réaction leucoérythroblastique a été observée dans 31,73 % (33/104) des cas, et une thrombocytopénie a été observée dans 25 % (26/104) des cas. La tumeur maligne la plus fréquente associée aux métastases de la moelle osseuse chez l'adulte était l'adénocarcinome de la prostate (28,1 %) (9/32) et, chez les enfants, le neuroblastome (53,9 %) (52/98). Conclusions: Il est essentiel de diagnostiquer les tumeurs malignes non hématologiques qui ontmétastasé à la moelle osseuse car cela nécessite une stadification tumorale, une sélection thérapeutique et une stratification du risque de pronostic. Pour conclure, pas un seul paramètre hématologique n'est prédictif des métastases de la moelle osseuse; Cependant, une anémie inexpliquée, une image sanguine leucoérythroblastique et une thrombocytopénie dans le sang périphérique devraient faire suspecter des métastases de la moelle osseuse en cas de tumeurs malignes non hématologiques. Mots-clés: Aspiration de moelle osseuse, biopsie de la moelle osseuse, métastases de la moelle osseuse, résultats hématologiques, immunohistochimie, tumeurs malignes non hématologiques, frottis sanguin périphérique.

Superior haplotypes of key drought-responsive genes reveal opportunities for the development of climate-resilient rice varieties.

Haplotype-based breeding is an emerging and innovative concept that enables the development of designer crop varieties by exploiting and exploring superior alleles/haplotypes among target genes to create new traits in breeding programs. In this regard, whole-genome re-sequencing of 399 genotypes (landraces and breeding lines) from the 3000 rice genomes panel (3K-RG) is mined to identify the superior haplotypes for 95 drought-responsive candidate genes. Candidate gene-based association analysis reveals 69 marker-trait associations (MTAs) in 16 genes for single plant yield (SPY) under drought stress. Haplo-pheno analysis of these 16 genes identifies superior haplotypes for seven genes associated with the higher SPY under drought stress. Our study reveals that the performance of lines possessing superior haplotypes is significantly higher (p ≤ 0.05) as measured by single plant yield (SPY), for the OsGSK1-H4, OsDSR2-H3, OsDIL1-H22, OsDREB1C-H3, ASR3-H88, DSM3-H4 and ZFP182-H4 genes as compared to lines without the superior haplotypes. The validation results indicate that a superior haplotype for the DREB transcription factor (OsDREB1C) is present in all the drought-tolerant rice varieties, while it was notably absent in all susceptible varieties. These lines carrying the superior haplotypes can be used as potential donors in haplotype-based breeding to develop high-yielding drought-tolerant rice varieties.

SpeedFlower: a comprehensive speed breeding protocol for indica and japonica rice.

To increase rice yields and feed billions of people, it is essential to enhance genetic gains. However, the development of new varieties is hindered by longer generation times and seasonal constraints. To address these limitations, a speed breeding facility has been established and a robust speed breeding protocol, SpeedFlower is developed that allows growing 4-5 generations of indica and/or japonica rice in a year. Our findings reveal that a high red-to-blue (2R > 1B) spectrum ratio, followed by green, yellow and far-red (FR) light, along with a 24-h long day (LD) photoperiod for the initial 15 days of the vegetative phase, facilitated early flowering. This is further enhanced by 10-h short day (SD) photoperiod in the later stage and day and night temperatures of 32/30 °C, along with 65% humidity facilitated early flowering ranging from 52 to 60 days at high light intensity (800 µmol m-2 s-1). Additionally, the use of prematurely harvested seeds and gibberellic acid treatment reduced the maturity duration by 50%. Further, SpeedFlower was validated on a diverse subset of 198 rice accessions from 3K RGP panel encompassing all 12 distinct groups of Oryza sativa L. classes. Our results confirmed that using SpeedFlower one generation can be achieved within 58-71 days resulting in 5.1-6.3 generations per year across the 12 sub-groups. This breakthrough enables us to enhance genetic gain, which could feed half of the world's population dependent on rice.

Comparative assessment of cleaning efficacy of two exclusive paediatric rotary files in root canals of primary teeth: An in vitro study.

BACKGROUND: Paediatric rotary file systems have recently been developed for primary teeth use. AIM: To study the cleaning efficacies of two paediatric rotary endodontic files, the Prime PedoTM, and the Kedo-SG BlueTM against the standard H files. DESIGN: This in vitro study included 54 freshly extracted primary molars, which were randomised into three groups (n = 18 each) and were prepared using either Kedo-SG BlueTM, Prime PedoTM or hand H files after injecting methylene blue dye into the canals. Pre- and post-operative cone beam computerised tomography (CBCT) was performed to assess change in root canal volumes. Methylene blue dye removal from canals was assessed using stereomicroscopy, and canal cleanliness was examined by scanning electron microscopy (SEM). RESULTS: Both Prime PedoTM and Kedo-SG BlueTM files reduced significantly less dentine when compared with conventional hand filing with Prime PedoTM removing the least amount of dentine. No significant difference was found in median SEM scores among the groups in the cervical, middle and apical thirds of the roots. Stereomicroscopic assessment of root canal cleanliness using dye removal technique shows a statistically significant difference existing between Kedo-SG BlueTM and hand H files groups. CONCLUSION: Prime PedoTM removed the least amount of dentine. Kedo-SG BlueTM performed significantly better than conventional hand filing with H files when the root canal cleanliness was assessed.

Extreme trait GWAS (Et-GWAS): Unraveling rare variants in the 3,000 rice genome.

Identifying high-impact, rare genetic variants associated with specific traits is crucial for crop improvement. The 3,010 rice genome (3K RG) dataset offers a valuable resource for discovering genomic regions with potential applications in crop breeding. We used Extreme Trait GWAS (Et-GWAS), employing bulk pooling and allele frequency measurement to efficiently extract rare variants from the 3K RG. This innovative approach facilitates the detection of associations between genetic variants and target traits, concentrating and quantifying rare alleles. In our study, on grain yield under drought stress, Et-GWAS successfully identified five key genes (OsPP2C11, OsK5.2, OsIRO2, OsPEX1, and OsPWA1) known for enhancing yield under drought. In addition, we examined the overlap of our results with previously reported qDTY-QTLs and observed that OsUCH1 and OsUCH2 genes were located within qDTY2.2 We compared Et-GWAS with conventional GWAS, finding it effectively capturing most candidate genes associated with the target trait. Validation with resistant starch showed similar results. To enhance user-friendliness, we developed a GUI for Et-GWAS; https://et-gwas.shinyapps.io/Et-GWAS/.

Comparison of acceptability & efficacy of thermal ablation (thermocoagulation) & cryotherapy in VIA positive cervical lesions: A pilot study.

BACKGROUND OBJECTIVES: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. METHODS: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. RESULTS: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). INTERPRETATION CONCLUSIONS: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

Utility of bone marrow examination in retinoblastoma and their correlation with hematological features.

Retinoblastoma makes up about 3% of all childhood malignancies. The frequency of metastatic retinoblastoma ranges from 4.8 to 11%. Assessing the bone marrow status of newly diagnosed patients is crucial because of the advantages of autologous bone marrow transplants for high-risk patients. This study aimed to determine the utility of bone marrow examination in cases of retinoblastoma and its correlation with hematological findings. This retrospective study was conducted at the Department of Pathology, King George's Medical University, Lucknow, India. A total of 34 cases of retinoblastoma with bone marrow examination were included in the study. Bone marrow infiltration was present in 17.65% (6/34) cases of retinoblastoma. Bone marrow aspirate myelogram showed that marrow metastasis in retinoblastoma was significantly linked with a reduced percentage of total myeloid cells (p=0.001) and segmented cells (p=0.006). The present study demonstrated that 15% (3/20) of retinoblastoma patients previously classified as nonmetastatic before bone marrow examination (stages I to III based on histology, imaging, and bone scan) had bone marrow metastases following bone marrow examination and were upgraded to stage IV. To conclude, a diligent and exhaustive search for metastatic cells in bone marrow is advised if the myelogram shows a reduced percentage of total myeloid and segmented cells. All stage II and stage III cases of retinoblastoma must undergo bone marrow examination for early metastasis detection, as it may result in an upgrade to stage IV disease, impacting the prognosis and necessitating distinct treatment modalities.

Solitary superficial angiomyxoma of the ear pinna: a diagnostic dilemma with a review of literature.

Superficial angiomyxoma is an extremely rare subcutaneously placed myxoid soft tissue neoplasm. There are few case reports with fine needle aspiration cytological and histopathological findings available for this tumor because of its rarity. Here, we describe a case of superficial angiomyxoma in a 24-year-old girl who had a solitary left ear pinna mass without a Carney's complex at the time of presentation or at the end of two years of follow-up next to the surgical removal of the tumor. The clinical, cytomorphological, and histological findings, together with the immunohistochemical markers, in a case of superficial angiomyxoma are described in this rare case report for the first time in the English literature.

Molecular and Morphological Characterization of Introgression Lines with Resistance to Bacterial Leaf Blight and Blast in Rice.

The present study evaluates marker assisted forward breeding (MAFB)-derived disease resistant introgression lines (ILs) which do not have the targeted resistance genes for bacterial blight (xa5 + xa13 + Xa21) and blast (Pi2 + Pi9 + Pi54). The ILs were derived in the background of two elite rice cultivars, Krishna Hamsa [Recurrent Parent 1 (RP1)] and WGL 14 (RP2), involving multi-parent inter-crossing. Molecular characterization with gene specific markers for seven reported resistance genes each for bacterial blight (Xa33, Xa38, xa23, Xa4, xa8, Xa27 and Xa41) and blast (Pi1, Pi20, Pi38, Pib, Pitp, Pizt and Pi40) revealed the presence of xa8 and Xa38, in addition to the targeted xa5, xa13 and Xa21 for bacterial blight resistance and Pi1, Pi38, Pi40, Pi20, Pib and Pipt, in addition to the targeted Pi9 and Pi54, for blast resistance in various combinations. A maximum of nine resistance genes xa5 + Xa21 + Pi54 + xa8 + Pipt + Pi38 + Pi1 + Pi20 + Pib was observed in RP1-IL 19030 followed by eight genes xa5 + xa13 + Xa21 + xa8 + Pi9 + Pipt + Pi1 + Pi20 in two RP2-ILs, 19344 and 19347. ANOVA revealed the presence of significant variability for all the yield traits except "days to 50% flowering" (DFF). Box plots depicted the seasonal differences in the phenotypic expression of the yield traits. There was significant positive association of grain yield with days to flowering, tiller number and panicle number. Thousand grain weight is also significantly and positively correlated with grain yield. On the contrary, grain yield showed a significantly negative association with plant height. Multi-parent selective inter-crossing in the present study not only led to the development of high yielding disease resistant ILs but also enhanced recovery of the recurrent parent via selection for essential morphological features. More than 90.0% genetic similarity in the ILs based on SNP-based background selection demonstrated the success of multi-parent selective intercrossing in the development of disease resistant NILs.

Post-mortem interval estimation using miRNAs of road traffic accident cases: A forensic molecular approach.

In forensic examination accurate estimation of post-mortem interval (PMI) is a challenging task, particularly in the advanced stages of decomposition. The existing methods (algor mortis, livor mortis, rigor mortis, putrefaction etc) used for estimating PMI rely on analyzing the physical, biochemical, and metabolic changes that occur in the corpse after death. While these methods have shown some level of effectiveness in estimating PMI during the early stages of decomposition, accurate estimation becomes increasingly challenging during the later stages of putrefaction when the body undergoes significant changes. Recently, microRNA (miRNA) profiling due to its relatively small size and stability has emerged as a promising tool in several areas of forensics. This study demonstrates the potential of miRNA for PMI estimation in advanced stages of death. In this study, miRNA-195, miRNA-206, and miRNA-378 were selected as target miRNAs and miRNA-1 as reference miRNA. Left ventricle tissue (5 g) of the heart from 20 forensic autopsies of traffic accident victims (18-32 years) were collected and processed. The samples were held at room temperature for eight different time intervals (12, 24, 48, 72, 96, 120, 168 and 196 h), and RNA was extracted from all the samples using Trizol-based RNA isolation protocol, followed by cDNA synthesis and amplification with commercially available specific miRNA probes in Real-Time PCR (RT-PCR), Ct was calculated. The result showed that miRNAs were associated with PMI. Over time, there were substantial changes in the Ct values of all three miRNAs, with significant reductions observed at 196 h compared to 12 h. miRNA-206 demonstrated significant changes at multiple time intervals, while miRNA-1 remained stable for up to 196 h and thus holds caas an endogenous marker. In conclusion, miRNA has the potential to serve as a valuable tool for estimating PMI, especially during the advanced stages of decomposition, when used in conjunction with established techniques. However, further validation of the study is required to obtain more accurate estimates of PMI.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.

Early and Effective Diagnosis of Sepsis Using Flow Cytometry.

Objective Sepsis is a major global health issue due to its high death and morbidity rates. To avoid the negative effects of sepsis and decrease mortality, it is vital to diagnose and treat it as soon as possible. Blood cultures can take up to 2 days to give result, and they are not always reliable. According to recent studies, neutrophil CD64 expression might be a sensitive and specific option for assessing sepsis. This study aimed to evaluate the diagnostic performance of a flow cytometry analysis for the expression of neutrophil CD64 in sepsis and its comparison with other standard tests in a tertiary care center. Materials and Methods Prospective analysis on 40 blood samples from suspected sepsis patients admitted to intensive care units with criteria for the systemic inflammatory response syndrome on presentation was performed for expression of neutrophil CD64, C-reactive protein, procalcitonin, and complete blood count. Ten healthy volunteers were also enrolled in this prospective study. The laboratory results were compared in different groups. Results The neutrophil CD64 had the highest diagnostic value to differentiate between patients of sepsis and nonsepsis groups with a sensitivity of 100% (95% confidence interval [CI]: 77.19-100%) and 100% (95% CI: 55.32-86.83%); specificity of 90.00% (95% CI: 59.58-99.49%) and 87.24% (95% CI: 66.69-99.61%); and likelihood ratio of 10.00 and 7.84, respectively. Conclusion The neutrophil CD64 expression provides a more sensitive, specific, and novel marker for the early detection of sepsis in critically ill patients.

Comparison of Demirjian and Cameriere methods and development of modified Cameriere and Demirjian formula more efficient for North Indian population.

Introduction: Accurate age estimation is of utmost importance in several branches of life, be it disaster victim identification (DVI), sports, fashion, education, and many more. Several studies/formulas have been proposed over the years from various parts of the world and amongst them, Cameriere's method of age estimation is now being accepted globally, and the related work is still one of the most thought about. Aim: The aim of this study was to access the relationship between dental age (DA) and chronological age using Cameriere and Demirjian age estimation method in the north Indian population and develop a population-specific regression formula and validate it in the north Indian population. Materials and Methods: Orthopantomograms (OPG) of 762 children of north India with age groups between 7 and 16 years were collected. Seven left permanent mandibular teeth were analyzed using both Cameriere and Demirjian's age estimation method. The resultant data were subjected to statistical analysis. Results: The mean differences between CAge and DAge with age were 1.21 (males), 0.14 (males) and 1.72 (females), 0.28 (females) respectively, which shows significant disparity, wherein Demirjian follows overestimation and Cameriere follows the underestimation trend. Therefore, we modified these methods using the linear regression model. Conclusion: The modified Demirjian and Cameriere formula after validation shows a better fit in the north Indian state of the Uttar Pradesh population.

Prodrug Strategies for the Development of ß-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU) against Varicella Zoster Virus (VZV).

Varicella zoster virus (VZV) establishes lifelong infection after primary disease and can reactivate. Several drugs are approved to treat VZV diseases, but new antivirals with greater potency are needed. Previously, we identified ß-l-5-((E)-2-bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU, 1), which had significant anti-VZV activity. In this communication, we report the synthesis and evaluation of numerous l-BHDU prodrugs: amino acid esters (14-26), phosphoramidates (33-34), long-chain lipids (ODE-l-BHDU-MP, 38, and HDP-l-BHDU-MP, 39), and phosphate ester prodrugs (POM-l-BHDU-MP, 41, and POC-l-BHDU-MP, 47). The amino acid ester l-BHDU prodrugs (l-phenylalanine, 16, and l-valine, 17) had a potent antiviral activity with EC50 values of 0.028 and 0.030 µM, respectively. The phosphate ester prodrugs POM-l-BHDU-MP and POC-l-BHDU-MP had a significant anti-VZV activity with EC50 values of 0.035 and 0.034 µM, respectively, and no cellular toxicity (CC50 > 100 µM) was detected. Out of these prodrugs, ODE-l-BHDU-MP (38) and POM-l-BHDU-MP (41) were selected for further evaluation in future studies.