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Introduction and Aim: Gram-negative bacterial infections have emerged as a global health problem in clinical care. They account for the majority of community and hospital acquired infections which are resistant to various antimicrobials. The present study aimed to investigate the prevalence and antibiotic susceptibility pattern of Gram-negative bacteria (GNB) isolated from various non-urinary samples at a tertiary care hospital in Haryana. Materials and Methods: A total of 228 isolates were obtained from various clinical samples from January 2018 to July 2018 and were identified by standard bacteriological techniques. Antibiotic susceptibility testing was done using the disc diffusion technique by the Kirby Bauer method. Results: Adult patients showed higher isolation of GNB (31%) as compared to paediatric patients (16.3%). The most common GNB isolated from blood was Pseudomonas spp.(62%) and Klebsiella spp.(66.7%) from respiratory samples isolated in our study showed resistance to common antibiotics like gentamicin and ceftriaxone. Polymyxin B and Tigecycline were found to be sensitive. Conclusion: Strict compliance with antimicrobial stewardship policy should be followed to reduce the menace of antibiotic resistance.

Background: Sepsis is a complex, life-threatening, heterogeneous infectious disease associated with increased rates of morbidity and mortality. Early assessment of the prognosis of sepsis is key to achieving a favorable outcome for the disease. This study aimed to identify the prognostic value of PCT for sepsis patients. Materials and Methods: We conducted a prospective analytical study involving 100 adult patients with sepsis who were admitted to the Medicine dept and intensive care unit from 2019 to 2020. At least one blood test for PCT level was performed for all patients within the first 24 hours of suspecting an infection. Results: Our study found that a maximum number of patients (43.0%) were between 51-60 years age group, mean age of the patient was 49.35 ± 11.7 years. Out of 100 cases, 65% were male and 35% were female. The male and female ratio was 1.85:1. In this study serum, procalcitonin levels 0.5-2.0 ng/were detected in 15.0% of patients with mean±SD 1.3±0.8. Serum procalcitonin levels 2.1-10.0 ng/mL were detected in 29.0% of patients with mean±SD 5.9±2.5 and >10.0 ng/mL was detected in 56 patients. Based on the receiver-operator characteristic (ROC) curves, procalcitonin had the area under curve 0.923, with 89.4% sensitivity and 87.5% specificity. In our study, procalcitonin showed the best predictive value for the short-term outcome of sepsis with a cut-off value of 14.8 ng/mL (AUC 0.923). Study shows that 76.0% of the patients recovered completely, but 24.0% of patients expired during the hospital stay. Conclusion: There was a statistically significant correlation in serum procalcitonin with the outcome of sepsis (p < 0.001). So the effectiveness of serum procalcitonin has proven significant in the prediction of mortality in sepsis patients. J MEDICINE 2023; 24: 18-22

Cancer can be fatal if it is not treated in a timely manner; therefore, there is a high demand for more specific oncology drugs. Unfortunately, drugs showing positive responses on a two‑dimensional (2D) culture platform do not often show the same effect in clinical trials. Therefore, three‑dimensional (3D) culture platforms are garnering attention since they more closely mimic the tumor microenvironment (TME). The TME stimulates metastasis and drug resistance, and serves an essential role in tumor formation. An accurate understanding of tumor‑stroma interactions is undoubtedly required to improve the response of patients to therapeutic strategies, and cancer therapeutic strategies that do not account for the stroma are considered inadequate. It should be noted that 3D monoculture systems do not completely mimic the TME since other cells in the 3D culture are missing, such as fibroblast or endothelial cells, which are essential components of the stroma; therefore, it is essential to develop advanced 3D culture systems. The present study aimed to develop a versatile triculture model that mimics the native TME; therefore, it could aid in high‑throughput screening of chemotherapeutic drugs against cancer by evaluating their effects on tumor progression and cell cytotoxicity. The present study demonstrated the use of the AXTEX‑4D™ platform in developing triculture tissueoids composed of MCF‑7, human umbilical vein endothelial cells and MRC5 cells, and compared it with a 3D monoculture model (MCF‑7) and a 2D culture model. The triculture model was validated for proliferation, ECM markers and T‑cell infiltration by confocal microscopy. Alamar Blue assay demonstrated that triculture tissueoids exhibited higher drug resistance than the other two models, thus demonstrating their use in the screening of oncology drugs.

Tuberculosis (TB) of lymph node (TB lymphadenitis) is one of the most common forms of extrapulmonary TB (EPTB) whose diagnosis is critically challenging. Although new diagnostic methods have been developed, especially in patients without a history of TB, the cervical tuberculous lymphadenitis diagnosis is still elusive. This study assessed the applicability of GeneXpert in early diagnosis of EPTB, especially cervical lymphadenopathy.The study was conducted in a tertiary care hospital from January 2018 to December 2020 at the department of microbiology. All the samples of cervical lymph node tissue and lymph node aspirate were followed as per the routine protocol for mycobacterial identification. The sample was divided into two parts: one was used for the new molecular-based GeneXpert MTB/RIF assay and the second one was tested by direct and concentrated acid-fast bacilli microscopy by Z-N staining and culture for the detection of MTB.Among the 145 samples tested, the GeneXpert detected the DNA of MTB in 89 samples (61.37%), whereas the culture test was positive in 42 (28.93%) specimens. GeneXpert also detected 7 rifampicin resistance cases. GeneXpert sensitivity and specificity results were assessed according to culture results. The sensitivity and specificity of the GeneXpert assay were 85.71% and 48.54%, respectively.GeneXpert MTB/RIF should be used in conjunction with clinical presentation and other molecular investigation in nonrespiratory specimens.

The formation of three-dimensional spheroid tumor model using the scaffold-based platforms has been demonstrated over many years now. 3D tumor models are generated mainly in non-scalable culture systems, using synthetic and biological scaffolds. Many of these models fail to reflect the complex tumor microenvironment and do not allow long-term monitoring of tumor progression. This has resulted in inconsistent data in drug testing assays during preclinical and clinical studies.To overcome these limitations, we have developed 3D tissueoids model by using novel AXTEX-4D platform.Cancer 3D tissueoids demonstrated the basic features of 3D cell culture with rapid attachment, proliferation, and longevity with contiguous cytoskeleton and hypoxic core. This study also demonstrated greater drug resistance in 3D-MCF-7 tissueoids in comparison to 2D monolayer cell culture.In conclusion, 3D-tissueoids are more responsive than 2D-cultured cells in simulating important tumor characteristics, anti-apoptotic features, and their resulting drug resistance.

INTRODUCTION:Aviation industry has been instrumental in globalisation by connecting the global countries through its fast transport network. By providing quick access to global markets it has helped in easing the international travel, international trade, foreign investments and tourism. Impact of aviation sector on the global economy is massive. According to Oxford Economics (as cited in Aviation Beyond Borders, 2016) in 2014 it generated $ 2.7 trillion, which is 3.5 per cent of global GDP. Had aviation been a country, it would have ranked 21st largest economy in terms of GDP, similar in size to Sweden or Switzerland (Oxford Economics as cited in Aviation Beyond Borders,2016). In the same year Air transport generated employment for 62.7 million people in the world (Oxford Economics as cited in Aviation Beyond Borders,2016). Total direct employment in the sector was 9.9 million (Aviation Beyond Borders, 2016). Another noteworthy fact is that the jobs in this sector are 3.8 times more productive than other jobs (Oxford Economics as cited in Aviation Beyond Borders, 2016). In 2014 3.3 billion passengers took the services of the world airlines and in 2015 the number rose to 3.57 billion (ICAO and IATA as cited in Aviation Beyond Borders, 2016). Air transport is widely used in the transportations of very high valued and also time sensitive items like perishable products. In terms of the volume of trade shipments its share is less than one per cent; but it is around 35 per cent by value (Aviation Beyond Borders, 2016).On January 1st 1914 the first ever scheduled flight with a paying passenger was launched. It was a historic moment as it marked an event that changed the way the world travelled. In the last 20 years the global connectivity city -pairs have now almost doubled and_exceeded 16,600 in 2015, 350 more than in 2014(IATA's Annual Review, 2016). Over that same period, average airfares have more than halved (after adjusting for inflation), which has been a major stimulus for trade, tourism, and Foreign Direct Investment associated with global supply chains. There is massive increase not only in terms of the number of passengers but also in terms of the profits of the airlines. 2014 was the fifth successive year of profitability it registered an aggregate net profit of $16.4 billion. The year 2015 generated $35.3 billion net ,after tax profit, which was more than double of what was generated in 2014(IATA's Annual Review, 2016). As can be seen from the table 1, strong growth is forecasted in the aviation industry 20 years from 2014. Forecast for the year 2034 expects an increase of more than 100 per cent for many of the indicators of the aviation industry.RESEARCH OBJECTIVES:The study has been conducted aiming to achieve the following objectives:* To show the contribution of aviation industry on employment generation and GDP of the global economy.* To discuss the major infrastructural developments that took place in the air transport sector in the various Emirates of the UAE.* To analyse the direct, indirect, induced and catalytic (tourism) impact of the aviation sector on the job creation and GDP generation in the economy of the UAE.* To discuss the scope of the aviation sector in future in the economy of UAE.RESEARCH METHODOLOGY:This study is descriptive in nature. Secondary data has been used to project the overall contribution of aviation industry on the global economy in general and on the economy of the UAE in particular; and to highlight the major development done and achievements made in this sector. Data for this study has been taken from the official websites of General Civil Aviation Authority (GCAA), Various airport authorities such as Abu Dhabi Airports Company (ADAC) and Dubai Airports Company (DAC), airlines like Etihad Airways, Emirates Airlines etc., various reports such as Air Transport Action Group's (ATAG) Aviation Benefits beyond Borders April 2016, various reports of International Air Transport Association (IATA), UAE's leading newspapers and other sources on the internet. …

Aminoacyl-tRNA synthetases are essential enzymes that transmit information from the genetic code to proteins in cells and are targets for antipathogen drug development. Elucidation of the crystal structure of cytoplasmic lysyl-tRNA synthetase from the malaria parasite Plasmodium falciparum (PfLysRS) has allowed direct comparison with human LysRS. The authors' data suggest that PfLysRS is dimeric in solution, whereas the human counterpart can also adopt tetrameric forms. It is shown for the first time that PfLysRS is capable of synthesizing the signalling molecule Ap4a (diadenosine tetraphosphate) using ATP as a substrate. The PfLysRS crystal structure is in the apo form, such that binding to ATP will require rotameric changes in four conserved residues. Differences in the active-site regions of parasite and human LysRSs suggest the possibility of exploiting PfLysRS for selective inhibition. These investigations on PfLysRS further validate malarial LysRSs as attractive antimalarial targets and provide new structural space for the development of inhibitors that target pathogen LysRSs selectively.

D-Tyrosyl-tRNATyrdeacylase (DTD) is an editing enzyme that removes D-amino acids from mischarged tRNAs. The crystal structure ofPlasmodium falciparumDTD (PfDTD) was determined using the iodide-SAD phasing method. Iodide-derivatized PfDTD crystals were obtained using the quick cryo-soaking procedure in which native crystals were soaked for a short period of 10–30 s in cryoprotectant solution containing 0.2–1 MNaI. Iodide-SAD data sets were collected to 3.3 and 2.74 Å resolution from PfDTD crystals that belonged to two different space groups,P43andP1, using an in-house X-ray copper-anode source. This is the first report to detail structure solution using low iodide anomalous signal, modest resolution and redundancy and average solvent content for SAD phasing of 984 and 1312 amino acids in the triclinicP1 and tetragonalP43space groups, respectively. A total of 85% and 56% of the residues were automatically built into the iodide-phased electron-density maps usingPHENIX AutoBuild. The structure of HEPES-bound PfDTD was subsequently determined by molecular replacement and refined to 2.83 Å resolution. The crystals obtained from various batches of crystallization trials of PfDTD exhibited polymorphism in terms of belonging to different crystal forms and space groups. Even within a given crystal system the unit-cell parameters showed high non-isomorphism. These packing variations were exploited in order to conduct a systematic study of conformational changes in PfDTD. It is shown that the disposition of a ten-residue insertion loop affects packing within the PfDTD crystals and seems to determine the non-isomorphism in unit-cell parameters. By tracking the changes in PfDTD unit cells, it was possible to map conformational differences within PfDTD that may be of significance for enzyme activity.

Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin’s remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.