Clinical relevance of glycosylation in triple negative breast cancer: a review.

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC. Alpha-L-fucosidase 1 (FUCA1) and Monocarboxylate transporter 4 (MCT4) have been identified as potential diagnostic and prognostic markers for TNBC. The glycosylation status of PD-L1 impacts the response to immune checkpoint blockade therapy in TNBC. Inhibiting fucosylation of B7H3 enhances immune responses and improves anti-tumor effects. Targeting glycosylated B7H4 and modulating estrogen metabolism through glycosylation-related mechanisms are potential therapeutic strategies for TNBC. Understanding the role of glycosylation in TNBC provides insights into disease mechanisms, diagnosis, and potential therapeutic targets. Further research in this field may lead to personalized treatment approaches and improved outcomes for TNBC patients.

Sacituzumab Govitecan as a Second-Line Treatment in Relapsed/Refractory Metastatic Triple-Negative Breast Cancer Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Chemotherapy, the only treatment option for metastatic triple-negative breast cancer (mTNBC), showed decreased survival rates. Trophoblast cell surface antigen-2 (Trop-2) could be a possible target for antibody-drug conjugates (ADCs). OBJECTIVE: Sacituzumab govitecan (SG), an anti-Trop-2 ADC for pretreating relapsed/refractory mTNBC patients, was studied to know the efficacy and safety profile of the drug in mTNBC. METHODS: The present review searched MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until December 25, 2022. The studies searched comprised randomized trials and observational studies (retrospective [case-control, cross-sectional] and prospective [cohort designs]). Efficacy assessment was performed in terms of complete response (CR), partial response (PR), objective response rate (ORR), stable disease (SD), progressive disease (PD), and clinical benefit rate (CBR), and safety in terms of adverse events. RESULTS: The overall random-effects pooled prevalence of CR was 4.9 (95% CI: 3.2-7.1), PR was 35.6 (95% CI: 31.5-39.9), ORR was 6.8 (95% CI: 5.9-7.8), SD was 8.0 (95% CI: 6.7-9.4), PD was 5.1 (95% CI: 4.1-6.3), and CBR was 13.4 (95% CI: 11.8-15.1). Adverse events associated with the drug were neutropenia, fatigue, anemia, nausea, and others. CONCLUSION AND RELEVANCE: This is the first meta-analysis conducted in relapsed/refractory mTNBC patients and found that SG is efficacious but associated with some adverse effects that are related to exposure to the drug. The application of these results will allow clinicians to use SG in the management of patients with mTNBC.

Plasma Proteomic Analysis Identified Proteins Associated with Faulty Neutrophils Functionality in Decompensated Cirrhosis Patients with Sepsis.

Decompensated cirrhosis (DC) is susceptible to infections and sepsis. Neutrophils and monocytes provide the first line of defense to encounter infection. We aimed to evaluate proteins related to neutrophils functionality in sepsis. 70 (DC), 40 with sepsis, 30 without (w/o) sepsis and 15 healthy controls (HC) plasma was analyzed for proteomic analysis, cytokine bead array, endotoxin, cell free DNA and whole blood cells were analyzed for nCD64-mHLADR index, neutrophils-monocytes, functionality and QRT-PCR. nCD64-mHLADR index was significantly increased (p < 0.0001) with decreased HLA-DR expression on total monocytes in sepsis (p = 0.045). Phagocytic activity of both neutrophils and monocytes were significantly decreased in sepsis (p = 0.002 and p = 0.0003). Sepsis plasma stimulated healthy neutrophils, showed significant increase in NETs (neutrophil extracellular traps) and cell free DNA (p = 0.049 and p = 0.04) compared to w/o sepsis and HC. Proteomic analysis revealed upregulated- DNAJC13, TMSB4X, GPI, GSTP1, PNP, ANPEP, COTL1, GCA, APOA1 and PGAM1 while downregulated- AHSG, DEFA1,SERPINA3, MPO, MMRN1and PROS1 proteins (FC > 1.5; p < 0.05) associated to neutrophil activation and autophagy in sepsis. Proteins such as DNAJC13, GPI, GSTP1, PNP, ANPEP, COTL1, PGAM1, PROS1, MPO, SERPINA3 and MMRN1 showed positive correlation with neutrophils activity and number, oxidative burst activity and clinical parameters such as MELD, MELD Na and Bilirubin. Proteomic analysis revealed that faulty functionality of neutrophils may be due to the autophagy proteins i.e., DNAJC13, AHSG, TMSB4X, PROS1 and SERPINA3, which can be used as therapeutic targets in decompensated cirrhosis patients with sepsis.

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis.

Background: Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood. Methods: A total of 164 decompensated cirrhotic-62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF-and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR. Results: Frequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival. Conclusion: MDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.

Immune Surveillance by Myeloid-Derived Suppressor Cells in Liver Diseases.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive in nature, originate in the bone marrow, and are mainly found in the blood, spleen, and liver. In fact, liver acts as an important organ for induction and accumulation of MDSCs, especially during infection, inflammation, and cancer. In humans and rodents, models of liver diseases revealed that MDSCs promote regeneration and drive the inflammatory processes, leading to hepatitis, fibrogenesis, and cirrhosis, ultimately resulting in hepatocellular carcinoma. SUMMARY: This brief review is focused on the in-depth understanding of the key molecules involved in the expansion and regulation of MDSCs and their underlying immunosuppressive mechanisms in liver diseases. KEY MESSAGE: Modulated MDSCs can be used for therapeutic purposes in inflammation, cancer, and sepsis.

Normal and reconstituted high-density lipoprotein protects differentiated monocytes from oxidized low-density lipoprotein-induced apoptosis.

BACKGROUND: The progression of atherosclerosis is an ongoing struggle between cell division and cell death. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a novel receptor for oxidized low-density lipoprotein (ox-LDL), mediates ox-LDL-induced apoptosis of monocytes. The anti-atherogenic function of plasma high-density lipoprotein (HDL) includes the ability to inhibit apoptosis of macrophage, although the exact mechanism and consequences of apoptosis in the development and progression of this disease are still controversial. Thus, in the present study, the effect of normal HDL (nHDL) and reconstituted HDL (rHDL) on ox-LDL-induced cellular responses in differentiated monocytes in view of apoptosis and LOX-1 receptor expression was investigated. METHODS: The expression of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), caspase-3, and cytochrome c (cyt c) was assessed and substantiated in 30 hyper-LDL and control subjects. To assess the expression of LOX-1 on differentiated THP-1 cells, western blotting was carried out, followed by statistical analysis in 30 patients and control subjects. RESULTS: nHDL/rHDL inhibited the ox-LDL-induced apoptosis in the differentiated human monocytic cells, THP-1 cells, and differentiated monocytes of patient and control subjects. Enhanced expression of scavenger receptor, LOX-1, in the differentiated monocytes was also downregulated in presence of nHDL/rHDL. nHDL/rHDL could inhibit the ox-LDL-induced mitochondrial apoptotic pathway and aberrant expression of LOX-1 in patients. Double immunostaining using fluorescein isothiocyanate (FITC)-conjugated ox-LDL and LOX-1 in apoptotic cells indicates its significant role in the differentiated monocytes. CONCLUSION: It was observed that nHDL/rHDL could promote macrophage survival by preserving mitochondrial integrity from ox-LDL-induced apoptosis.

Radiological Manifestations of Pulmonary Tuberculosis - A Comparative Study between Immunocompromised and Immunocompetent Patients.

INTRODUCTION: Pulmonary tuberculosis has atypical radiological manifestations in patients with underlying immunocompromised disease like diabetes and human immunodeficient virus infection. Computed tomography has important role in such patients for early diagnosis of disease and management to minimize complication. AIM: To evaluate and compare the computed tomography chest features of pulmonary tuberculosis in between immunocompromised patients and immunocompetent patients. MATERIALS AND METHODS: This cross-sectional study was conducted in the hospital on newly diagnosed 60 pulmonary tuberculosis patients of which 30 patients had no underlying disease (Immunocompetent Group) and 30 patients had diabetes mellitus or were human immunodeficiency virus seropositive (Immunocompromised Group). CT scan of chest were evaluated for each patient. RESULTS: In immunocompetent patients, 36.7% had radiologically atypical presentation,90% had nodular opacities, 73.3% had consolidation, 23.3% had lymphadenopathy, 60% had cavitation and cavitatory lesion were single in 94.4% patients. Isolated upper lung field were involved in 60% patients. In immunocompromised patients 76.7% had radiologically atypical presentation, 66.7% had nodular opacities, 46.7% had consolidation, 63.3% had lymphadenopathy, 20% had cavitation and cavitatory lesions were multiple in 60% patients. Isolated lower lung field were involved in 23.3% patients. CONCLUSION: We concluded that immunocompromised patients have more atypical involvement of lung fields, higher prevalence of lymphadenopathy as compared to immunocompetent patients. Diabetic patients have multiple cavitatory lesions as compared to non-diabetic patients. HIV seropositive patients have more prevalence of lymphadenopathy as compared to HIV seronegative patients.

Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours.

INTRODUCTION: IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. AIM: To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. MATERIALS AND METHODS: A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. RESULTS: Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. CONCLUSION: IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use.

Pleural and Mediastinal Lipomatosis with Subpleural Fat as a Mimicker of Pleural Effusion- A Rare Case Report.

Subpleural and mediastinal lipomatosis are benign intrathoracic conditions discovered incidentally on plain chest radiographs. However, diagnosis is usually made by Computed Tomography (CT). A case of both mediastinal and pleural lipomatosis associated with use of steroids in a 58-year-old male patient presented with complaints of breathlessness and dry cough is discussed in this case report. Intially, pleural effusion and bilateral upper lobe patchy opacities were suspected as a cause of breathlessness on the basis of chest x-ray findings. For which, CT scan of chest was advised.

Role of Computed Tomography (CT) in Localisation and Characterisation of Suprahyoid Neck Masses.

BACKGROUND: Suprahyoid neck lesions are difficult to assess only by means of clinical inspection and therefore imaging techniques are required to precisely evaluate suprahyoid neck spaces. The aim of this study was to evaluate the distinctive role of computed tomography in the assessment of anatomical source and pathological type of masses involving the suprahyoid neck spaces. MATERIAL/METHODS: Sixty patients presenting with suprahyoid neck masses underwent computed tomography of the neck. The CT findings were correlated with histopathological findings and a final diagnosis was made. RESULTS: Overall, male preponderance was seen except in the case of parotid space lesions where female predominance was seen. The most common aetiology was squamous cell carcinoma and the majority of cases (30%) were seen in patients aged 41-50 years. The majority of lesions were found in the pharyngeal mucosal space (n=16) with squamous cell carcinoma being the most common pathology. In the parotid space, pleomorphic adenoma and in the prestyloid parapharyngeal space, squamous cell carcinoma were the most common lesions, respectively. In the retropharyngeal space, an equal incidence of malignant and inflammatory aetiologies was seen. Abscesses were the most common lesions in the prevertebral space. The pleomorphic adenoma was the most common benign tumour and was also the second most common tumour in the suprahyoid neck spaces. CT had an excellent correlation with histopathological findings with sensitivity of 96.4%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 91.67%. CONCLUSIONS: Computed tomography definitely has a major role to play in the evaluation of suprahyoid neck masses as it has an excellent correlation with post-operative histopathological diagnosis.

Role of Echocardiography in Prenatal Screening of Congenital Heart Diseases and its Correlation with Postnatal Outcome.

INTRODUCTION: Congenital Heart Defects (CHDs) are one of the most common forms of congenital anomalies. Fetal echocardiography performed during second trimester aims at early diagnosis of congenital heart disease which is instrumental in proper planning of delivery, perinatal care and counselling of parents. AIM: To evaluate the role of fetal echocardiography in prenatal screening of CHDs and to study the role of associated extracardiac anomalies. MATERIALS AND METHODS: This was a hospital based prospective and correlative type of study, done over a period of one year. Antenatal screening of fetal heart was done in mid-trimester high and low risk pregnancies. The prenatal echo findings were co-related with postnatal findings in case of any abnormality detected. The extra-cardiac anomalies associated with positive cases were evaluated and studied for their impact on postnatal outcome. RESULTS: A total of 1200 pregnancies were screened out of which 672 were low risk and 528 were high risk. The cases with abnormal echo findings were followed postnatally. The overall incidence of CHD in study population was 15 per 1000. The incidence in high and low risk pregnancies were 16.3 and 13.25 per thousand respectively. Complete agreement of 68.17% was found between prenatal and postnatal findings. The most frequent Extra-Cardiac Anomalies (ECA) in cases with CHD was of musculoskeletal system. The CHD cases with ECA were significantly of low birth weight, born preterm and delivered by Lower Segment Caesarean Section (LSCS). CONCLUSION: Fetal heart is the most overlooked part in every routine anomaly scan. We conclude that fetal echocardiography should be an integral part of every second trimester anomaly scan for all pregnant females irrespective of their risk factors. The associated ECAs are another factor that causes increased mortality both in antenatal and neonatal life, again warranting an early fetal echo.

Colour Doppler Evaluation of Extracranial Carotid Artery in Patients Presenting with Acute Ischemic Stroke and Correlation with Various Risk Factors.

INTRODUCTION: Stroke is defined as an abrupt onset of neurologic deficit due to vascular cause. It is one of the leading causes of mortality and morbidity all over the world making early diagnosis and treatment inevitable. Lesions of extra cranial carotid arteries are implicated in majority of cases of acute ischemic stroke. Carotid Doppler is a non-invasive imaging technique, with sensitivity approaching that of angiography. Computed Tomography (CT) plays a major role to assess the site and nature of the lesion in patients with acute ischemic stroke. AIM: To evaluate the role of carotid Doppler sonography in patients presenting with acute ischemic stroke and find association between carotid artery stenosis and risk factors such as diabetes mellitus, hypertension, hyperlipidemia, smoking and age. MATERIALS AND METHODS: The present study was conducted on 50 patients. CT scan was done to diagnose acute ischemic stroke in patients who presented to emergency medicine with symptoms of acute ischemic stroke. Retrospectively CIMT and plaque characterization were done by gray scale ultrasound. Site and severity of stenosis were assessed on colour Doppler. All these findings were correlated with clinical presentation and risk factors. The collected data was statistically analyzed and multivariant logistic regression (R-value) test of significance was applied by using SPSS 16.0 version software. RESULTS: On carotid Doppler, ICA/CCA PSV ratio was good predictor of stenosis and ratio above three indicates significant stenosis (>60%). Carotid bulb was most common location of plaque formation. Hypertension and diabetes were the most prevalent risk factors for cerebral ischemic stroke. Out of total 50 patients, 32 had hypertension (64%) and 22 had diabetes (44%). Hypertension and hyperlipidemia showed maximum mean R-values (0.275 and 0.048 respectively) and positive correlation with stenosis and increased CIMT in acute ischemic stroke patients. CONCLUSION: The present study highlights the importance of Doppler sonography in acute ischemic stroke patients through surveillance of atherosclerosis.

Evaluation of anti-inflammatory effects of systemically administered curcumin, lycopene and piperine as an adjunct to scaling and root planing: A clinical study.

BACKGROUND: The natural herbal extracts curcumin (Curcuma longa), lycopene and piperine demonstrated a very potent anti-inflammatory action and can be used as an antioxidant therapy in the management of inflammatory processes such as gingivitis and periodontitis. AIM AND OBJECTIVE: The aim of the present study is to evaluate the effects of systemically administered extracts curcumin, lycopene and piperine as an adjunct to scaling and root planing (SRP) in patients with moderate gingivitis. MATERIALS AND METHODS: Sixty systemically healthy participants with moderate gingivitis were enrolled in a randomized clinical study. Participants were randomly distributed into two treatment groups: Group I (test group) (350 mg/day antioxidant therapy) along with SRP for 3 weeks and Group II (control group) SRP alone. Clinical parameters such as plaque index, gingival index and probing pocket depth were evaluated at baseline and after 21 days using paired t-test. RESULTS: Both the treatment groups showed statistically significant reduction in clinical parameters, but the test group showed greater reduction as compared to control group (P < 0.05). CONCLUSION: The results concluded that systemically administered antioxidants could cause better resolution of inflammation when used as an adjunct to SRP.

Disseminated hydatidosis with rare presentation as "cystovesical fistula".

Disseminated hydatidosis is a rare disease and may involve any organ of the human body. In this case, an elderly female got infected by Echinococcus and presented with disseminated disease. A fistulous communication developed between one of the hydatid cysts present in the retrovesical region and the bladder, because of which the patient presented with hydatiduria.

A study to evaluate the correlation of serum albumin levels with chronic periodontitis.

CONTEXT: Periodontitis is a chronic inflammatory disease caused by bacterial infection of the supporting tissues around the teeth. Serum albumin levels might be the practical marker of general health status. Albumin concentration is associated with nutrition and inflammation. AIMS: The aim of this study was to evaluate the relationship between periodontal health status and serum albumin levels. SUBJECTS AND METHODS: A total of 60 subjects of both genders with age range of 40-70 years were included in the study. Patients were divided into two groups viz. Group I; clinically healthy subjects and Group II; patients with chronic periodontitis, that is, loss of attachment ≥5 mm. Serum albumin concentration was estimated by bromocresol green albumin method. STATISTICAL ANALYSIS USED: Student's unpaired t-test. RESULTS: The mean value of serum albumin levels for Group I was 4.815 g/dL with standard deviation (SD) of 0.127 and for Group II, the mean value of serum albumin levels was 4.219 g/dL (SD 0.174). The difference between serum albumin levels in Group I and Group II were found to be statistically significant ( P ≤ 0.001). CONCLUSIONS: The findings of this clinical trial suggest an inverse relationship between the serum albumin concentration and chronic periodontal disease.

Is periodontal health a predictor of drug-induced gingival overgrowth? A cross-sectional study.

BACKGROUND: Gingival overgrowth is a common side-effect of amlodipine regimen on the oral cavity. There is controversy regarding the cause and effect relationship of periodontal health and drug induced gingival overgrowth. Therefore, this study was conducted to investigate and to assess the relationship between the periodontal health and the onset and severity of gingival overgrowth in hypertensive patients receiving amlodipine. MATERIALS AND METHODS: A total of 99 known hypertensive patients on amlodipine regimen were included in this study. Probing pocket depth (PPD) and clinical attachment loss (CAL) were noted on four sites of maxillary and mandibular anterior teeth. Gingival enlargement scores were assessed for each patient by employing the hyperplastic index. Oral hygiene status was evaluated using the calculus index (CI). Patients were divided into H, E and L groups based on their periodontal status and responders and non-responders based on their hyperplastic index scores. Differences in means of different periodontal variables in different groups were tested for significance by using ANOVA and unpaired Student t-test. Pearson's correlation coefficient was calculated to assess the correlation between different variables. For all analyses, P < 0.05 was considered to be significant. RESULTS: All the periodontal parameters were statistically highly significant (P = 0.00) amongst H, E and L groups and between responders and non-responders. Statistically highly significant Pearson correlation coefficients were found between mean PPD and mean hyperplastic score, mean CAL and mean hyperplastic score and mean calculus and mean hyperplastic score. CONCLUSION: The results of this study indicated a definite association between periodontal health and development and severity of amlodipine-induced gingival overgrowth.

GSIT: An integrated web-tool for identification of genomic signatures in highly similar DNA sequences.

UNLABELLED: Accurate identification and characterization of infectious agent and its subtype is essential for efficient treatment of infectious diseases on a target population of patients. Comparative biology of microbial populations in vitro and in vivo can identify signatures that may be used to develop and improve diagnostic procedures. Here we report Genomic Signature Identification Tool (GSIT) a web based tool for identification and validation of genomic signatures in a group of similar DNA sequences of microorganisms. GSIT uses multiple sequence alignment to identify the unique base sites and scores them for inclusion as genomic signature for the particular strain. GSIT is a web based tool where the front-end in designed using HTML/CSS and Javascript, while back-end is run using CGI-Perl. AVAILABILITY: The server is freely available at the http://genome-sign.net/gsit.

Mutation profiling of the hepatitis B virus strains circulating in North Indian population.

AIMS: The aim of this study was to investigate the genomic mutations in the circulating Hepatitis B virus strains causing infection in the Indian population. Further, we wanted to analyze the biological significance of these mutations in HBV mediated disease. METHODS: 222 HBsAg positive patients were enrolled in the study. The genotype and mutation profile was determined for the infecting HBV isolate by sequencing overlapping fragments. These sequences were analyzed by using different tools and compared with previously available HBV sequence information. Mutation Frequency Index (MFI) for the Genes and Diagnosis group was also calculated. RESULTS: HBV Genotype D was found in 55% (n = 121) of the patient group and genotype A was found in 30% (n = 66) of samples. The majority (52%) of the HBV-infected individuals in the present study were HBeAg-negative in all the age groups studied. Spontaneous drug associated mutations implicated in resistance to antiviral therapy were also identified in about quarter of our patients, which is of therapeutic concern. The MFI approach used in the study indicated that Core peptide was the most conserved region in both genotypes and Surface peptide had highest mutation frequency. Few mutations in X gene (T36A and G50R) showed high frequency of association with HCC. A rare recombinant strain of HBV genotype A and D was also identified in the patient group. CONCLUSIONS: HBV genotype D was found out to be most prevalent. More than half of the patients studied had HBeAg negative disease. Core region was found to be most conserved. Drug Associated mutations were detected in 22% of the patient group and T36A and G50R mutations in X gene were found to be associated with HCC.

Improving the Peri-operative care of Patients by instituting a 'Block Room' for Regional Anaesthesia.

Regional anaesthesia has multiple known benefits over general anaesthesia alone, but requires time and expertise for its application. This study aimed to decrease anaesthetic time and increase total surgical operative time by instituting a 'block room' where regional anaesthesia nerve blocks could be provided by expert anaesthetists in regular scheduled sessions. A baseline audit showed that 2 hours per day was spent on performing nerve blocks. Development of the block room allowed nerve blocks to be performed in parallel to surgical operations, reducing the mean anaesthetic control time from 44 mins to 27 mins. This freed time for an extra operative case per day. In addition, pooling of expertise to one site has allowed excellent teaching opportunities for anaesthetic trainees, and a specific training programme for regional anaesthesia is being produced. In conclusion, instituting a block room has improved the efficiency of our theatre complex, and improved the service deliverable to our patients.

Identification of druggable targets for Acinetobacter baumannii via subtractive genomics and plausible inhibitors for MurA and MurB.

Emergence of the multidrug-resistant pathogens has rendered the current therapies ineffective thereby, resulting in the need for new drugs and drug targets. The accumulating protein sequence data has initiated a drift from classical drug discovery protocols to structure-based drug designing. In the present study, in silico subtractive genomics approach was implemented to find a set of potential drug targets present in an opportunist bacterial pathogen, Acinetobacter baumannii (A. baumannii). Out of the 43 targets identified, further studies for protein model building and lead-inhibitor identification were carried out on two cell-essential targets, MurA and MurB enzymes (of A. baumannii designated as MurAAb and MurBAb) involved in the peptidoglycan biosynthesis pathway of bacteria. The homology model built for each of them was further refined and validated using various available programs like PROCHECK, Errat, ProSA energy plots, etc. Compounds showing activity against MurA and MurB enzymes of other organisms were collected from the literature and were docked into the active site of MurAAb and MurBAb enzymes. Three inhibitors namely, T6361, carbidopa, and aesculin, showed maximum Glide score, hydrogen bonding interactions with the key amino acid residues of both the enzymes and acceptable ADME properties. Furthermore, molecular dynamics simulation studies on MurAAb-T6361 and MurBAb-T6361 complexes suggested that the ligand has a high binding affinity with both the enzymes and the hydrogen bonding with the key residues were stable in the dynamic condition also. Therefore, these ligands have been propsed as dual inhibitors and promising lead compounds for the drug design against MurAAb and MurBAb enzymes.