Molecular Identification of Carbapenem Resistance Acinetobacter baumannii causing Ventilator-Associated Pneumonia Isolated from Intensive Care Unit of Tertiary Care Hospital

Ventilator-associated pneumonia (VAP) is a serious complication in critically ill patients, significantly increasing morbidity and mortality. One concerning organism behind VAP is Acinetobacter baumannii, a multidrug-resistant bacterium has ability to evade treatment, particularly with carbapenems, the last-line antibiotics. This is especially worrisome within the confines of Intensive Care Units (ICUs) of tertiary care hospitals, hubs for high-risk patients and potential reservoirs of antimicrobial resistance. This study focused on identifying carbapenem-resistant Acinetobacter baumannii using both phenotypic and genotypic methods. In 132 isolates of Acinetobacter baumannii, we observed 96% resistance to the cephalosporins while least resistance found to colistin and tigecycline. However, a concerning 51.5% of isolates exhibited carbapenem resistance. Phenotypically confirmation of carbapenem resistance detected in 47% isolates by Combined Disc Test and 51.5% isolates by Modified Hodge Test and E-test. Genotypic analysis with RT-PCR revealed a diverse array of resistance genes: blaIMP (33.82%), blaVIM (25%), blaOXA-Group (20.58%), and blaNDM (8.82%). These findings highlight the alarming prevalence of carbapenem-resistant Acinetobacter baumannii in healthcare settings

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Bacteriological Profile with antibiogram of Ventilator Associated Pneumonia in an intensive care unit of tertiary care hospital.

Background: Ventilator associated Pneumonia is a common hospital acquired infection that occurs more than 48 hrs of mechanical ventilation (MV). VAP shows high incidence and mortality in ICU’s and become threat to the patients undergoing treatment.Material &amp; Method: A prospective study over three years included patients on Ventilator and clinically diagnosed as VAP. Quantitative cultures were made from the endotrachel aspirates, collected from the patients. The bacterial isolates were identified as per laboratory protocol. Antimicrobial detection tests were performed by the Kirby Bauer Disc Diffusion Method.Result: A total number of 300 Endo-tracheal (ET) secretion samples were collected from the patients with the suspected ventilator associated pneumonia and processed as per laboratory protocol. Single isolate was grown in 85% which represents the magnitude of VAP. It was observed that 112 (43.9 %) isolates were identified in early VAP patients and 143 (56.07%) isolates were identified from late VAP patients. The predominant gram negative isolate was Acinetobacter spp. 122 (41%) followed by Klebsiella spp 52 (20.39%), Pseudomonas spp. 47 (18.43%), Escherichia coli 32 (12.54%), Enterobacter aerogens 7 (2.74%) and Citrobacter spp. 5 (1.96%).  Among the gram negative bacilli, 36.8% were resistant to Imipenem,, 67.8% resistant to cefoperazone- sulbactam and 87.4% resistant to Ceftazidime. All gram negative isolates were sensitive to Colistin, Polymixin B and Tigecycline.Conclusion: A local antibiogram pattern for each hospital is required to start empirical therapy based on bacteriological profile and susceptibility. This study may help clinicians in prescribing appropriate antimicrobials

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Computational investigations into structure and function impact of novel mutations identified in targeted exons from ovarian cancer cell lines

The lack of sensitive and specific biomarkers for ovarian cancer leads to late stage diagnosis of the disease in a majority of the cases. Mutation accumulation is the basis for cancer progression, thus identifying mutations is an important step in the disease diagnosis. In the present study, a comprehensive analysis of fifteen Next Generation Sequencing samples from thirteen ovarian cancer cell lines was carried out for the identification of new mutations. The study revealed eight clinically significant novel mutations in six ovarian cancer oncogenes, viz. SMARCA4, ARID1A, PPP2R1A, CTNNB1, DICER1 and PIK3CA. In-depth computational analysis revealed that the mutations affected the structure of the proteins in terms of stability, solvent accessible surface area and molecular dynamics. Moreover, the mutations were present in functionally significant domains of the proteins, thereby adversely affecting the protein functionality. PPI network for SMARCA4, CTNNB1, DICER1, PIK3CA, PPP2R1A and ARID1A showed that these genes were involved in certain significant pathways affecting various hallmarks of cancer. For further validation, in vitro studies were performed that revealed hypermutability of the CTNNB1 gene. Through this study we have identified some key mutations and have analysed their structural and functional impact. The study establishes some key mutations, which can be potentially explored as biomarker and drug target. Communicated by Ramaswamy H. Sarma</p

Role of itraconazole in the management of aspergillosis in treated patients of pulmonary tuberculosis

Sputum/ bronchial washings of 445 patients with residual tubercular cavitation were subjected to smear and culture examination to isolate fungi. Patients suffering from aspergillosis were put on oral itraconazole daily for 6 months and monitored clinicoradiologically during and after therapy. About half of the patients of aspergilloma and 85&#x0025; of the patients of chronic necrotizing pulmonary aspergillosis improved by 3 months of therapy. Nausea and headache observed during therapy in 8 and 4 patients respectively were mild and self limiting. Relapses were seen in 8 out of the 37 patients who had completed 6 months therapy and available for follow-up

An unusual recurrent case of Cryptococcal sacroiliitis in an immunocompetent elderly female in Rajasthan, India

A 70-year-old female presented with left sided low back pain. There was no history of any co-morbidities or immunocompromised state. Skeletal cryptococcosis was confirmed bsaed on culture and histopathology, along with pulmonary involvement. After a month of oral antifungal therapy, the patient's symptoms resolved, but an abscess relapsed at the same site, which was treated with a combination of IV Amphotericin B and 5-flucytosine followed by oral fluconazole, with no recurrence or complaints reported in subsequent follow-up

Clinical profile of pulmonary aspergilloma complicating residual tubercular cavitations in Northen Indian patients

<b>Background:</b> Little is known regarding the clinical profile of Aspergilloma in Indian patients. Such a study was undertaken at Hospital for Chest and TB, Jaipur. <b>Materials and Methods:</b> Old, treated patients of pulmonary tuberculosis showing ball like lesion/s inside cavity/ies or a recent thickening of cavity wall were enrolled. Morning sputa samples were collected in the patients who were able to raise sputum and were examined by KOH mount and fungal culture. Serum anti-aspergillus antibodies were estimated in all the patients. Twenty normal healthy subjects were included to serve as control. All patients showing a positive or borderline positive serology were diagnosed as pulmonary aspergilloma (PA group). The remaining patients formed the non-aspergilloma group (Non PA group). <b>Results:</b> A total of 98 study patients could be classified as PA group (54 patients by serology alone, 44 patients by serology as well as sputum culture). The remaining 152 patients were classified as non PA group. Hemoptysis alone or along with other chest symptoms was significantly more common in PA group as compared to non PA group patients (<i>P</i>&lt;0.001), more so in those with ball like lesions. But chest symptoms other than hemoptysis were more common in non PA group. Within the PA group, 21 (13 with ball like lesions and 8 with thickening of cavity wall) had clinical symptoms suggestive of CNPA and two patients (one each with ball like lesions and thickening of cavity wall) had clinical symptoms suggestive of ABPA. <b>Conclusion:</b> The clinical profile of pulmonary Aspergilloma in Indian patients is very protean ranging from saprophytic disease to CNPA and less commonly to ABPA