SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK WITH AND WITHOUT DEXAMETHASONE AS AN ADJUVANT TO LOCAL ANESTHETICS- AN OBSERVATIONAL STUDY.

Aim: Branchial plexus block accompanied by bupivacaine gives very efficacious anesthesia and analgesia. The addition of dexamethasone as an additive in bupivacaine prolonged the anesthetic and analgesic effect. This study aimed to contrast the outset and period of sensory and motor blockade and the period of the analgesic effect after adding dexamethasone to anesthesia and anesthesia without adding dexamethasone in the Supraclavicular branchial plexus block. Materials and Methods: This study included 100 patients and was conducted in Cuttack, Odisha. The age group of patients was between 20-60 years. Patients were divided into 2 categories:         Category 1 (cases): In this group, 16 ml of 2% lignocaine with adrenaline was administered and 16 ml of 0.5% bupivacaine with 10mg dexamethasone was administered.         Category 2 (control): In this group, 16 ml of 2% lignocaine with adrenaline was administered and 16 ml of 0.5% bupivacaine with saline was administered. Results: In Category 1 the sensory blockage was outset in 7 minutes whereas in Category 2 the outset of sensory blockage was 14 minutes. The motor blockage in Category 1 started in 4 minutes and in Category 2 it started in 19 minutes. There was no complication during the operative period and post-operatively. Conclusion: The addition of dexamethasone in 16 ml of 2 % lignocaine with adrenaline and 16 ml of 0.5% bupivacaine with 10mg dexamethasone increases the outset of sensory and motor blockage. It significantly increases the period of sensory and motor blockage and duration of analgesia. Recommendation: The in-plane approach is strongly recommended for this block; the needle tip and shaft should be continuously visualised in real-time to avoid inadvertent pleural puncture

A prospective observational study of prevalence, incidence, and prognostic implications of right-sided heart failure in acute respiratory distress syndrome patients

Background: Acute respiratory distress syndrome (ARDS) is a common reason for respiratory failure in critically unwell patients. Noncardiogenic pulmonary edoema that develops suddenly, acute hypoxemia, and the need for mechanical ventilation are its defining features. This study's major objective was to examine the likelihood of cor-pulmonale in ARDS patients receiving protective ventilation, as well as its prognosis over the long term. Methods: S. C. B. medical college in Odisha, India served as the setting for this prospective observational study. 100 consecutive patients with moderate to severe ARDS were included in the trial in accordance with the Indian criterion. With an average PEEP of 91 cm H2O and a plateau pressure cap of 31 cm H2O, these patients were ventilated. Results: There were 100 patients altogether, 63 males and 37 females, with a mean age of 59-19 years. The interval between the diagnosis of ARDS and TEE was typically 0.75-0.97 days. There were 100 cases of cor pulmonale, which was shown to be common (21.09%). Lung injury occurred more frequently in patients with cor pulmonale compared to other patients when an infectious cause was involved [37 (79.06%) vs. 67 (57.61%)]. Conclusions: The incidence of cor pulmonale in ARDS patients undergoing ventilation with restricted airway pressure is an interesting finding. In our investigation, it showed up as an independent risk factor for 28-day mortality and was linked to sepsis and high driving pressure readings

Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma

Introduction: Younger women with breast carcinoma (BC) exhibits more aggressive pathologic features compared to older women; young age could be an independent predictor of adverse prognosis. To find any existing differences in the molecular pathogenesis of BC in both younger and older women, alterations at chromosomal (chr.) 9q22.32-22.33 region were studied owing to its association in wide variety of tumors. Present work focuses on comparative analysis of alterations of four candidate genes; PHF2, FANCC, PTCH1 and XPA located within 4.4 Mb region of the afore-said locus in two age groups of BC, as well as the interrelation and prognostic significance of alterations of these genes. Methods: Deletion analysis of PHF2, FANCC, PTCH1 and XPA were examined in a subset of 47 early-onset (group-A: ≤ 40 years) and 59 late-onset (group-B: > 40 years) breast carcinomas using both microsatellite and exonic markers. Methylation Sensitive Restriction analysis (MSRA) was done to check for promoter methylation. Quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemisty (IHC) was done in some genes to see their relative mRNA and protein expressions respectively. Clinico-pathological correlation of different parameters as well as patient survival was calculated using different statistical softwares like EpiInfo 6.04b, SPSS 10.0 etc. Results: Either age group exhibited high frequency of overall alterations in PHF2, FANCC and PTCH1 compared to XPA. Samples with alteration (deletion/methylation) in these genes showed reduced level of mRNA expression as seen by Q-PCR. Immunohistochemical analysis of FANCC and PTCH1 also supported this observation. Poor patient survival was noted in both age groups having alterations in FANCC. Similar result was also seen with PTCH1 and XPA alterations in group-A and PHF2 alterations in group-B. This reflected their roles as prognostic tools in the respective groups in which they were altered. Conclusion: Overall alterations of PHF2, FANCC and PTCH1 were comparatively higher than XPA. Differential association of alterations in FANCC and PTCH1 with that of PHF2, XPA and two breast cancer susceptibility genes (BRCA1/BRCA2) in the two age groups suggests differences in their molecular pathogenesis and dysregulation of multiple DNA repair pathways as well as hedgehog dependent stem cell renewal pathway

Inhibition of nucleoporin member Nup214 expression by miR-133b perturbs mitotic timing and leads to cell death

Background: Nucleoporins mediate nucleocytoplasmic exchange of macromolecules and several have been assigned active mitotic functions. Nucleoporins can participate in various mitotic functions like spindle assembly, kinetochore organisation and chromosome segregation- important for genome integrity. Pathways to genome integrity are frequently deregulated in cancer and many are regulated in part by microRNAs. Indeed, altered levels of numerous microRNAs have frequently been associated with tumorigenesis. Here, we unveil a microRNA-mediated regulation of the nucleoporin Nup214 and its downstream effect on genome integrity. Methods: Databases/bioinformatic tools such as miRBase, Oncomine and RNAhybrid predicted Nup214 as a miR-133b target. To validate this, we used luciferase reporter assays, Real-Time PCR and immuno-blotting. Flow cytometry and immuno-blots of mitotic markers were used to analyse cell cycle pattern upon thymidine synchronization and miR-133b treatment. Mitotic indices and chromosomal abnormalities were assessed by immuno-fluorescence for FITC-tagged phospho-H3 as well as video-microscopy for GFP-tagged histone H4. Annexin V/propidium iodide staining, caspase3/ PARP cleavage and colony formation assays were done to investigate cell death upon either miR-133b transfection or NUP214 knockdown by siRNA. UPCI:SCC084, HCT116, HeLa-H4-pEGFP and HEK293 (human oral squamous cell carcinoma, colorectal, cervical carcinomas and embryonic kidney cell lines, respectively) were used. miR-133b and NUP214 expressions were validated in cancer cell lines and tissues by Real-Time PCR. Results: Examination of head and neck tumour tissues and cancer cell lines revealed that Nup214 and miR-133b expressions are negatively correlated. In vitro, Nup214 was significantly downregulated by ectopic miR-133b. This downregulation elevated mitotic indices and delayed degradation of mitotic marker proteins cyclinB1 and cyclinA and dephosphorylation of H3. Moreover, this mitotic delay enhanced chromosomal abnormalities and apoptosis. Conclusions: We have identified NUP214, a member of the massive nuclear pore complex, as a novel miR-133b target. Thus, we have shown a hitherto unknown microRNA regulation of mitosis mediated by a member of the nucleoporin family. Based on observations, we also raise some hypotheses regarding transport-dependent/independent functions of Nup214 in this study. Our results hence attempt to explain why miR-133b is generally downregulated in tumours and lay out the potential for Nup214 as a therapeutic target in the treatment of cancer

Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ

Lung cancer has emerged as one of the leading causes of cancer death in most developed and many developing countries of the world. In the absence of effective screening and early detection methods of lung cancer and overall poor prognosis, the 5-year survival following treatment has not improved significantly over the last two decades. It is hoped that the risk of the disease can be minimized by preventive measures. One aspect of lung cancer prevention emphasizes the cessation of tobacco smoking, and another strategy envisages reversal or restriction of the process of lung carcinogenesis by chemopreventive intervention. The latter strategy, however, demands a deeper understanding of the pathogenesis of the disease and the identification of the ideal point of intervention. In the present investigation, we assessed the role of the antioxidant tea components theaflavins (TF) and epigallocatechin gallate (EGCG) for their chemopreventive potential and molecular mechanism of action when administered at the post-initiation phase of lung carcinogenesis in an experimental mouse model. We serially examined the histopathological changes in the lung of mice administered benzo(a)pyrene and correlated them with the frequency of proliferative and apoptotic cells in situ as well as with the expression of H-ras, c-Myc, p53, and Bcl-2 genes, which play key roles in the histopathogenesis of neoplasia. Our findings indicate that both TF and EGCG can influence gene expression to modulate the process of carcinogenesis through the regulation of apoptosis. This results in a lowered incidence and delayed onset of preinvasive lung lesions

Approximately 580Kb surrounding the MYC gene is amplified in head and neck squamous cell carcinoma of Indian patients

Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). However, there are no data concerning whether the amplification is confined to the MYC gene itself or spans distant 5' and/or 3' regions of this gene in HNSCC as seen in different lymphomas, colon carcinoma, and uterine cervical carcinoma (CaCx). In this study, we analyzed the alterations (amplification/rearrangement) in the 580 Kb surrounding of the MYC gene to understand the status of this locus in primary HNSCC of Indian patients. The MYC alterations were analyzed by Southern blot using the pal-1/MYC/MLVI4 probes. The alterations in the MYC locus (adjacent region of the c-myc gene) were then correlated with the various clinicopathological parameters. The overall amplification involving the MYC locus was seen in 46% of the samples. The MYC gene, pal-1 region, and MLVI4 region were amplified in about 38%, 24%, and 20% of the samples, respectively. Some samples showed co-amplification encompassing pal-1-MYC-MLVI4 or pal-1-MYC or MYC-MLVI4 regions. No significant association was observed between the amplification in the MYC locus and the different clinicopathological parameters except for tumor differentiation. Thus, it seems that, similar to other tumors, the MYC gene may be activated by amplification in its surrounding 5' and/or 3' region in HNSCC

Anomalous altered expressions of downstream gene-targets in TP53-miRNA pathways in head and neck cancer

The prevalence of head and neck squamous cell carcinoma, HNSCC, continues to grow. Change in the expression of TP53 in HNSCC affects its downstream miRNAs and their gene targets, anomalously altering the expressions of the five genes, MEIS1, AGTR1, DTL, TYMS and BAK1. These expression alterations follow the repression of TP53 that upregulates miRNA-107, miRNA- 215, miRNA-34 b/c and miRNA-125b, but downregulates miRNA-155. The above five so far unreported genes are the targets of these miRNAs. Meta-analyses of microarray and RNA-Seq data followed by qRT-PCR validation unravel these new ones in HNSCC. The regulatory roles of TP53 on miRNA-155 and miRNA-125b differentiate the expressions of AGTR1 and BAK1in HNSCC vis-a`-vis other carcinogenesis. Expression changes alter cell cycle regulation, angiogenic and blood cell formation, and apoptotic modes in affliction. Pathway analyses establish the resulting systems-level functional and mechanistic insights into the etiology of HNSCC

Inactivation of SLIT2-ROBO1/2 Pathway in Premalignant Lesions of Uterine Cervix: Clinical and Prognostic Significances

The SLIT2-ROBO1/2 pathways control diverse biological processes, including growth regulation. To understand the role of SLIT2 and ROBO1/2 in cervical carcinogenesis, firstly their RNA expression profiles were screened in 21 primary uterine cervical carcinoma (CACX) samples and two CACX cell lines. Highly reduced expressions of these genes were evident. Concomitant alterations [deletion/methylation] of the genes were then analyzed in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN, SLIT2 was deleted in 22% samples compared to 9% for ROBO1 and none for ROBO2, whereas comparable methylation was observed for both SLIT2 (30%) and ROBO1 (22%) followed by ROBO2 (9%). In CACX, alteration of the genes were in the following order: Deletion: ROBO1 (48%) > SLIT2 (35%) > ROBO2 (33%), Methylation: SLIT2 (34%) > ROBO1 (29%) > ROBO2 (26%). Overall alterations of SLIT2 and/or ROBO1 (44%) and SLIT2 and/or ROBO2 (39%) were high in CIN followed by significant increase in stage I/II tumors, suggesting deregulation of these interactions in premalignant lesions and early invasive tumors. Immunohistochemical analysis of SLIT2 and ROBO1/2 in CACX also showed reduced expression concordant with molecular alterations. Alteration of all these genes predicted poor patient outcome. Multiparous (≥5) women with altered SLIT2 and ROBO1 along with advanced tumor stage (III/IV) and early sexual debut (<19 years) had worst prognosis. Our data suggests the importance of abrogation of SLIT2-ROBO1 and SLIT2-ROBO2 interactions in the initiation and progression of CACX and also for early diagnosis and prognosis of the disease