Inclusion of carbohydrate antigen 242 in addition to carbohydrate antigen 19.9 in serological workup of carcinoma gall bladder: a case series analysis

Background: Common antigenic pool is seen because of shared embryonic origins of gall bladder cancer (GBC) and pancreas. Hence, we analyzed the role of serum carbohydrate antigen 242 (CA242) which has been studied in pancreatic cancer, in GBC. The objectives were to identify whether serum CA242 provides added advantage in diagnosis of GBC when compared to controls and to determine its cut-off value. Methods: Serum CA 19-9 level was determined by chemiluminescent micro particle assay and CA242 by enzyme linked immunosorbent assay (ELISA) of age matched cases and controls. Results: Total enrolled patients were 83 including 10 (11.7%) healthy volunteers, 22 (25.9%) chronic cholecystitis cases, and 53 (62.4%) patients with histological evidence of carcinoma. Mean age of presentation of GBC was 51.64 SD10.88 years with F: M ratio of 5.6:1. Pain (90.6%, 48/53) accompanied with jaundice was significantly associated with GBC well reflected by significantly raised serum total bilirubin (p=0.011), direct bilirubin (p=0.008) along with alkaline phosphatase levels (p=0.001). Significantly higher median value of CA 19-9 and CA242 was observed in GBC when compared to CC and healthy volunteers (p<0.001) with a significant correlation between tumor size (>2.5 cm) and serum levels of CA242. The best cut-off limit for CA242 was 45.25 IU/ml. The specificity for carcinoma diagnosis increased to 100% when CA242 was included along with CA 19.9 in serological estimation. Conclusions: We recommend that CA antigen 19-9 may be complimented with CA242 for serological identification of malignancy in the gall bladder

Clinicopathological and immunohistochemical analysis of Sarcomatoid carcinoma of head and neck mucosal region: a retrospective analysis

Background: Sarcomatoid carcinoma is a biphasic tumour comprising both of malignant epithelial and mesenchymal elements derived monoclonally from same stem cells. These are unusual variants of squamous cell carcinoma and constitute less than 1% of the head and neck mucosal tumors. Only few studies have been published and needs more understanding to establish treatment guidelines. The aim of this study was to review the cases of carcinosarcoma arising from mucosal sites of head and neck and study their clinical, histological and Immunohistochemical features.Methods: Retrospective data and slides of histologically proven sarcomatoid carcinoma over a period of thirty -four months between January 2016 - October 2018 were retrieved and evaluated for various clinical and histopathological parameters.Results: Total of 22 cases were included in the study and the mean age of presentation was 58years with male: female ration 2:1. Most of the patients (81.8%) presented with a mass lesion of less than 6 months duration. The most common site was oral cavity (68.1%) followed by larynx (22.7%). Clinical stage was known in eleven cases. One case presented with pulmonary metastasis. Histopathologically, epithelial differentiation was identified in nine cases (41%) on morphology and in thirteen cases could be highlighted by cytokeratin positivity. The Mesenchymal component was arranged in sheets (63.7%) and fascicles (31.8%). Marked anaplasia and brisk mitosis wereseen in 54.5% and 19.3% respectively.  On immunohistochemistry all 22 cases were positive for Vimentin, twenty cases were positive for cytokeratin/EMA and aberrant mesenchymal markers were expressed in 10% of cases.  Follow up was available in eighteen cases out of which fourteen cases died within one year of diagnosis.Conclusions: Diagnosis of sarcomatoid carcinoma is challenging especially on small biopsy because of overlapping features with other spindle cell tumors. Understanding the clinicopathological features facilitates their diagnosis and effective clinical management

β2M Signals Monocytes Through Non-Canonical TGFβ Receptor Signal Transduction.

Rationale: Circulating monocytes can have pro-inflammatory or pro-reparative phenotypes. The endogenous signaling molecules and pathways that regulate monocyte polarization in vivo are poorly understood. We have shown that platelet derived beta-2 microglobulin (β2M) and transforming growth factor beta (TGFβ) have opposing effects on monocytes by inducing inflammatory and reparative phenotypes respectively, but each bind and signal through the same receptor. We now define the signaling pathways involved. Objective: To determine the molecular mechanisms and signal transduction pathways by which β2M and TGFβ regulate monocyte responses both in vitro and in vivo. Methods and Results: Wild-type (WT) and platelet specific β2M knockout (Plt-β2M-/-) mice were treated intravenously with either β2M or TGFβ to increase plasma concentrations to those in cardiovascular diseases. Elevated plasma β2M increased pro-inflammatory monocytes, while increased plasma TGFβ increased pro-reparative monocytes. TGFβ receptor (TGFβR) inhibition blunted monocyte responses to both β2M and TGFβ in vivo. Using imaging flow cytometry, we found that β2M decreased monocyte SMAD2/3 nuclear localization, while TGFβ promoted SMAD nuclear translocation, but decreased noncanonical/ inflammatory (JNK and NFκB nuclear localization). This was confirmed in vitro using both imaging flow cytometry and immunoblots. β2M, but not TGFβ, promoted ubiquitination of SMAD3 and SMAD4, that inhibited their nuclear trafficking. Inhibition of ubiquitin ligase activity blocked noncanonical SMAD-independent monocyte signaling and skewed monocytes towards a pro-reparative monocyte response. Conclusions: Our findings indicate that elevated plasma β2M and TGFβ dichotomously polarize monocytes. Furthermore, these immune molecules share a common receptor, but induce SMAD-dependent canonical signaling (TGFβ) versus non-canonical SMAD-independent signaling (β2M) in a ubiquitin ligase dependent manner. This work has broad implications as β2M is increased in several inflammatory conditions, while TGFβ is increased in fibrotic diseases.pre-print3451 K

Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India

Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi

Receptor Determinant Analogues for All 9-O-Ac-Sialoglycan-Recognizing Corona Viruses

In present study, analogues of receptor determinants were identified, which can mimic 9-O-Acsialoglycan-recognition by viruses and its usage in antiviral. It is well known that receptor determinants are part of host cell surface receptors which are recognized by virus surface glycoprotein as the first interaction of the target cell. This recognition governs the further processes of viral infection. Similar to other influenza viruses, Corona virus also processes through mechanisms of host interaction. This hostvirus interaction involves a conserved domain at interaction component of virus, which is known to be a key component during the process of virus infection. Therefore in the present study profile of possible Pharmacophore of conserved domain was used as a filter to identify analogues of receptor determinant from database ZINC database. The identified molecules were re-observed among the applicability domain defined by existing antiviral drugs as well as natural existing receptor determinant with sialic acid. The identified molecule needs to be further evaluated through in-vitro experiments. </p

Successful Aging among Senior Adults Across Age Residing in Lucknow City

Research Background: Successful Aging among Senior Adults is an important area of concern that reflects their overall aging and how they deal with it. Objective: The aim of the present investigation was to study Successful Aging among Senior Adults. Methods: The study was conducted on a Purposive Random Sampling of 120 respondents who were selected from Lucknow city in the age ranging from 65 to more than 75 years of which 67 men and 53 women. “Successful Aging Scale” Questionnaire which are prepared by Reker, 2009 is used to measure Successful Aging, the questionnaire was administered. The data were coded, tabulated, and analyzed. The data obtained were subjected to statistical analyzed using mean, frequency percentage. Result: The finding of the study revealed that the majority of respondents are Successfully Aged and the study also reveals that there is no significant difference between the Successful Aging of respondents and their Gender

Quality of Life among Senior Adults across Gender Residing in Lucknow City

Background: The quality of life among senior adults is an important area of concern which reflects the health status and well-being this vulnerable group. Objectives: The aim of the present investigation was to study the quality of life among senior adults. Methods: The study was conducted on a purposive random sampling of 120 respondents who were selected from Lucknow city in the age ranging from 65 to more than 75 years of which 67 men and 53 women. (OPQOL-35) “Older People’s Quality of Life” questionnaire which is prepared by A Bowling was used to measure the quality of life, the questionnaire was administered. The data were coded, tabulated, and analyzed. The data obtained were subjected to statistical analyzed using mean, frequency percentage, F test, and χ2 test using SPSS (version 20.0). Results: The finding of the study revealed that majority of respondents has good and alright quality of life. The result also revealed that there was no significant difference between quality of life of respondents across gender

Post-Translation Modifications and Mutations of Human Linker Histone Subtypes: Their Manifestation in Disease

Linker histones (LH) are a critical component of chromatin in addition to the canonical histones (H2A, H2B, H3, and H4). In humans, 11 subtypes (7 somatic and 4 germinal) of linker histones have been identified, and their diverse cellular functions in chromatin structure, DNA replication, DNA repair, transcription, and apoptosis have been explored, especially for the somatic subtypes. Delineating the unique role of human linker histone (hLH) and their subtypes is highly tedious given their high homology and overlapping expression patterns. However, recent advancements in mass spectrometry combined with HPLC have helped in identifying the post-translational modifications (PTMs) found on the different LH subtypes. However, while a number of PTMs have been identified and their potential nuclear and non-nuclear functions explored in cellular processes, there are very few studies delineating the direct relevance of these PTMs in diseases. In addition, recent whole-genome sequencing of clinical samples from cancer patients and individuals afflicted with Rahman syndrome have identified high-frequency mutations and therefore broadened the perspective of the linker histone mutations in diseases. In this review, we compile the identified PTMs of hLH subtypes, current knowledge of the relevance of hLH PTMs in human diseases, and the correlation of PTMs coinciding with mutations mapped in diseases

Analysis and optimization of mass percentage of zycoprint polymer and abrasives in achieving stability of suspension mixture in abrasive water jet machining

The suspension parameters are vital in the suspension-type abrasive water jet (AWJ) machining of several engineering materials, more so in difficult-to-cut materials, because it significantly influences the suspension stability and sedimentation behaviour of the suspension mixture and abrasive particle acceleration into the AWJs. The suspension stability and abrasive particle acceleration of the suspension-type AWJs are improved by using polymer additives. Hence, it is necessary to study the effect of suspension parameters (abrasive and polymer concentrations) on suspension stability. In this direction, the novel work reported in the paper analyses the stability of suspension by varying the mass percentage of abrasives (garnet and aluminum oxide (Al2O3)) (ωa) and mass percentage of the zycoprint polymer (ωp) in water by considering the Taguchi L9 Orthogonal array (OA). The linear regression (LR) models for the percentage of suspension volume with garnet (VsG) and the percentage of suspension volume with Al2O3 (VsA), are developed. The JAYA algorithm is used to find the optimal combination of the suspension parameters, and its results are in close agreement with the findings from the LR results. The optimum setting of the suspension parameters for both, VsG and VsA, is 3% of ωa and 0.80% of ωp

Experimental investigation and parametric optimization of cryogenic abrasive water jet machining of nitrile rubber using Taguchi analysis

AbstractMining/marine bushings, biomedical implants, and many more are among the several applications of lightweight elastomer components. The use of non-traditional machining to manufacture these good-quality components in small or batch-size units is required because the primary manufacturing method requires customised mould and follow-up machining. In this regard, the present work focuses on investigating the performance of machining a nitrile rubber (NR) using suspension-type abrasive water jet (AWJ) under both conventional (room temperature) and cryogenic (liquid nitrogen (LN2)) conditions at optimal values of process parameters: water jet pressure (WJP, bar), transverse rate (Vf, mm/min), and stand-off distance (SOD, mm). The experimental runs are designed using Taguchi analysis with respective performance parameters: Kerf taper ratio (KTR) and Material removal rate (MRR, mm3/min). The results show that Vf (Rank 1) is the highest influencing factor on the machining performance of NR under both conditions. The reasons are improved kinetic energy, less collision of garnet abrasive particles and lesser change in the average width of the kerf. The influence of LN2 showed that the optimal values of KTR reduced by 11.97% at 200 bar, 40 mm/min, and 1 mm, and MRR increased by 0.65% at 250 bar, 60 mm/min, and 2.0 mm, respectively