The genomic landscape associated with resistance to aromatase inhibitors in breast cancer

Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)–positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients’ responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

Anesthetic Management of A Patient with Hypertrophic Cardiomyopathy Posted For Non朇ardiac Surgery � Case Report

Hypertrophic cardiomyopathy (HOCM) is a complex cardiac disorder of genetic origin. Though the patients may be asymptomatic the stress of surgery and anaesthesia is known to exacerbate the left ventricular outflow tract (LVOT) obstruction leading to catastrophic complications. We hereby report a successful anaesthetic management of a patient with left intertrochantric fracture diagnosed with HOCM. Careful and meticulous strategies to prevent LVOT obstruction led to entire uneventful introperative and perioperative course.

Peripheral ameloblastoma of the gingiva

Peripheral Ameloblastoma (PA) is a benign odontogenic tumor, arising from the cell rest of Serres, reduced enamel epithelium and basal cells of the surface epithelium. Peripheral ameloblastoma is a rare odontogenic neoplasm occurring commonly in the mandibular gingiva. PA clinically resembles other peripherally occurring lesions like pyogenic granuloma, peripheral ossifying fibroma, peripheral giant cell granuloma, and squamous papilloma. The recurrence rate of PA is 16-19% which demands a straight follow up. We report a case of recurrent peripheral ameloblastoma occurring in a 72-year old male located in the mandibular lingual gingiva in relation to the 44, 45 element's regions. The patient had a primary lesion excised from the same site 6 years before which was diagnosed as ameloblastoma.

Exploration on the Effectiveness of Radio Frequency Treatment and Flash Pasteurisation on Enzyme and Microbial Activity for Coconut Water Preservation

The aim of this research work is to explore the effect of flash pasteurisation (FP) and radio frequency (RF) treatment on enzyme activity, microbial activity and physicochemical properties of matured coconut water (MCW). The process conditions for FP were treatment temperature and time in combinations. The process conditions for RF treatment were different electrode position with constant current load 0.8 A. The results obtained from these treatments reveal that FP conditions had significant effect on inactivation of natural microbial flora, polyphenoloxidase (PPO) and peroxidase (POD) activity. From the results it is observed that FP at 90°C for 10 minutes is better for complete enzyme and microbial inactivation than RF treated MCW. The result is also evident that PPO has higher thermal stability than POD. From observed results the study also concludes that, FP is a better option for enzyme and microbial inactivation but RF treatment was found superior for retaining physicochemical attributes.

Seminal reactive oxygen species and total antioxidant capacity: Correlations with sperm parameters and impact on male infertility / 대한생식의학회지

OBJECTIVE: The aim of this study was to measure reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in the seminal fluid of the male partners in couples undergoing intrauterine insemination and to evaluate correlations between these values and their semen parameters. METHODS: The study was conducted at Vamsam Fertility Center, Coimbatore, India and enrolled 110 male patients from whom semen samples were collected. ROS production was measured by a thiobarbituric acid reactive species assay, and TAC was measured by a 2,2-diphenyl-2-picrylhydrazyl free radical assay. The differences in the TAC and malondialdehyde (MDA) levels between the subfertile and fertile groups were analysed. Correlations between sperm parameters and TAC and MDA levels were statistically analysed, and cutoff values with respect to the controls were determined. All hypothesis tests used were two-tailed, with statistical significance assessed at the level of p < 0.05. RESULTS: A total of 87 subfertile and 23 fertile men were included in the study. The mean MDA level was significantly higher in the subfertile subjects than in the fertile subjects, and the mean antioxidant level was significantly lower in the subfertile subjects than in the fertile subjects. Seminal MDA levels were negatively associated with sperm concentration, motility, and morphology, whereas the opposite was seen with TAC levels. CONCLUSION: Measurements of seminal TAC and ROS are valuable for predicting semen quality, and hence predicting the outcomes of fertility treatment.

Neurological melioidosis presenting as intracranial abscess.

Melioidosis is an emerging disease in our country caused by the bacteria Burkholderia pseudomallei. Melioidosis can virtually affect any organ. It has varying clinical presentations ranging from pneumonia to fatal sepsis. Central nervous system (CNS) involvement in melioidosis is rare. We present a case of CNS melioidosis from South India. As the incidence of diabetes is increasing in our country varying manifestations of melioidosis will be seen in routine clinical practice. Melioidosis should be considered in the differential diagnosis of intracranial abscess and meningoencephalitis, especially in diabetics.

Clinical study of carbapenem sensitive and resistant Gram‑negative bacteremia in neutropenic and nonneutropenic patients: The first series from India.

OBJECTIVE: Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. MATERIALS AND METHODS: Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram‑negative bacteremia, identified over a period of 1‑year was done by medical records review, in Apollo Specialty Hospital, a 300‑bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. RESULTS: Of the total 141 patients with Gram‑negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). CONCLUSION: This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia.

Susceptibility profile of Gram‑negative bacteremic isolates to beta lactam‑beta lactamase inhibitor agents in comparison to other antibiotics.

BACKGROUND: Comprehensive understanding about the local antibiogram is an essential requirement for preparation of hospital or unit based antibiotic policy. Bacteremic isolates are the most useful ones for this purpose, representing invasive disease. OBJECTIVE: To analyze susceptibility pattern of bacteremic Gram‑negative isolates in our center, to various antibiotics, including beta lactam‑beta lactamase inhibitor (BL‑BLI) agents and carbapenem. MATERIALS AND METHODS: This is a retrospective study done in Apollo Specialty Hospital, a tertiary care oncology center in South India. The susceptibility of Escherichia coli, Klebsiella, Acinetobacter and Pseudomonas blood culture isolates, identified between January 2013 and June 2014 to various antibiotics were analyzed. RESULTS: A total of 231‑Gram‑negative bacteremic isolates were analyzed. ESBL rate among E. coli isolates was 82.7% (67 out of 81) and 74.3% (58 out of 78) in Klebsiella. Carbapenem (imipenem) susceptibility rate in E. coli was 76.5%, Klebsiella 58.9%, Acinetobacter 32% and Pseudomonas 77.2%. Colistin susceptibility in E. coli was 96.2%, Klebsiella 93.5%, Acinetobacter 92.8% and Pseudomonas 97.7%. Difference in the susceptibility of Enterobacteriaceae to BL‑BLI agents (especially cefepime‑tazobactam) and carbapenem were minimal. In nonfermenters, BL‑BLI susceptibility was better than that of carbapenem. CONCLUSION: Findings of the study make a strong argument for using BL‑BLI agents and sparing carbapenem to curtail the spiraling scenario of carbapenem resistance.

Antibacterial activity of Parmelia perlata

Objective: To test efficacy of Parmelia perlata (P. perlata), which is used in traditional medicine for rapid wound healing against test bacteria that cause wound infections. Methods: Different solvents such as methanol, ethyl acetate and acetone were used for extraction of P. perlata. The sensitivity of the test bacteria to solvent extracts of P. perlata was tested by measuring the zone of inhibition on growth media and by determining the minimal inhibitory concentration and minimal bactericidal concentration. Results: Methanol, ethyl acetate and acetone extracts of P.perlata have shown inhibitory activity against Staphylococcus aureus (S.aureus). Conclusions: The results of the present study indicate that P. perlata has potential antibacterial compounds againstS.aureus that causes multitude of skin infections among human beings. Development of drugs from natural compounds can help us to combat antibiotic-resistant bacteria.

Salmonella myocarditis presenting as acute myocardial infarction: a case report.

Cardiac involvement with Salmonella infection is well known and electrocardiographic changes bear a direct relationship to prognosis. We present here a case with ECG changes mimicking an acute myocardial infarction in salmonella infection.

Melioidosis: an under-diagnosed entity in western coastal India: a clinico-microbiological analysis.

Clinico-microbiological analysis of a series of 25 patients with culture proven melioidosis was done. All patients came from the coastal regions of Kerala and Karnataka and presented between June 2005 to July 2006. They were analysed with respect to clinical presentation, occupation, epidemiology and microbiological features. No single presenting clinical feature was found to be typical of melioidosis. The disease was found to mimic a variety of conditions, including tuberculosis and malignancy. Burkholderia pseudomallei was isolated from blood, sputum, pus, urine, synovial, peritoneal and pericardial fluids. Diabetes mellitus was the most common predisposing factor and 80% of the cases presented during the Southwest monsoon (June to September). It is probable that melioidosis is highly prevalent in western coastal India and yet, greatly underestimated. Better awareness, both among clinicians and microbiologists, coupled with improved diagnostic methods to allow early diagnosis and hence early treatment, will significantly reduce the morbidity and mortality associated with this disease.