Lactate Dehydrogenase Like Crystallin: A Potentially Protective Shield for Indian Spiny-Tailed Lizard (Uromastyx hardwickii) Lens Against Environmental Stress?

Taxon specific lens crystallins in vertebrates are either similar or identical with various metabolic enzymes. These bifunctional crystallins serve as structural protein in lens along with their catalytic role. In the present study, we have partially purified and characterized lens crystallin from Indian spiny-tailed lizard (Uromastyx hardwickii). We have found lactate dehydrogenase (LDH) activity in lens indicating presence of an enzyme crystallin with dual functions. Taxon specific lens crystallins are product of gene sharing or gene duplication phenomenon where a pre-existing enzyme is recruited as lens crystallin in addition to structural role. In lens, same gene adopts refractive role in lens without modification or loss of pre-existing function during gene sharing phenomenon. Apart from conventional role of structural protein, LDH activity containing crystallin in U. hardwickii lens is likely to have adaptive characteristics to offer protection against toxic effects of oxidative stress and ultraviolet light, hence justifying its recruitment. Taxon specific crystallins may serve as good models to understand structure-function relationship of these proteins

Comparison of Bacterial Load measured by X-pert / MTB RIF Assay with Smear & Myco-Bacterial Culture, as a marker for monitoring disease outcome in Cavitary Pulmonary Tuberculosis

Introduction: Tuberculosis (TB) is one of the major public health problems in Pakistan. Treatment depends on the diagnosis and bacterial load. The smear and culture of the sputum sample are considered as the gold standard. However, another recently invented diagnostic criteria i.e. X-PERT / MTB RIF Assay can also give high accuracy and can be used as a substitute for sputum culture. Objective: To determine the validity of Xpert MTB/RIF and sputum smear in monitoring the outcome of cavitary pulmonary tuberculosis by taking culture as the gold standard Study design: Descriptive Cross-sectional Study. Setting: Department of Pulmonology, Fauji Foundation Hospital Rawalpindi. Duration: 15th Feb to 15th Dec 2018. Materials and Methods: 250 Patients who meet the criteria were integrated into the study. A sputum sample was taken two times and two samples were sent to the laboratory of the hospital for Xpert MTB/RIF, sputum smear, and culture. Findings were recorded. Then patients were given standard treatment for tuberculosis. Data was entered in SPSS 23. Age, laboratory variables like HB, Platelets count, etc. were presented as mean and standard deviation. Gender, outcome of diagnosis were presented as mean and standard deviation. Sensitivity, specificity measure on –rays, findings, smear test, and Xpert MTB/RIF. Results: Total 187 patients including 12 (6.4%) male and 175 (93.6%) female. The mean age was 44.14+17.13 years. Positive findings on X-pert and smear were found in 35(53%) patients and MTB/ RIF were found in 41(62.1%). Sensitivity, specificity of X-pert MTB/RIF were found to be 77.6% and 13.6% at baseline while 40% and 40% respectively at end of treatment. Conclusion: Thus, X-pert MTB/RIF is an important tool than sputum smear and AFB culture in monitoring the outcome of cavitary pulmonary tuberculosis

Comparison of Bacterial Load measured by X-pert / MTB RIF Assay with Smear & Myco-Bacterial Culture, as a marker for monitoring disease outcome in Cavitary Pulmonary Tuberculosis

Introduction: Tuberculosis (TB) is one of the major public health problems in Pakistan. Treatment depends on the diagnosis and bacterial load. The smear and culture of the sputum sample are considered as the gold standard. However, another recently invented diagnostic criteria i.e. X-PERT / MTB RIF Assay can also give high accuracy and can be used as a substitute for sputum culture. Objective: To determine the validity of Xpert MTB/RIF and sputum smear in monitoring the outcome of cavitary pulmonary tuberculosis by taking culture as the gold standard Study design: Descriptive Cross-sectional Study. Setting: Department of Pulmonology, Fauji Foundation Hospital Rawalpindi. Duration: 15th Feb to 15th Dec 2018. Materials and Methods: 250 Patients who meet the criteria were integrated into the study. A sputum sample was taken two times and two samples were sent to the laboratory of the hospital for Xpert MTB/RIF, sputum smear, and culture. Findings were recorded. Then patients were given standard treatment for tuberculosis. Data was entered in SPSS 23. Age, laboratory variables like HB, Platelets count, etc. were presented as mean and standard deviation. Gender, outcome of diagnosis were presented as mean and standard deviation. Sensitivity, specificity measure on –rays, findings, smear test, and Xpert MTB/RIF. Results: Total 187 patients including 12 (6.4%) male and 175 (93.6%) female. The mean age was 44.14+17.13 years. Positive findings on X-pert and smear were found in 35(53%) patients and MTB/ RIF were found in 41(62.1%). Sensitivity, specificity of X-pert MTB/RIF were found to be 77.6% and 13.6% at baseline while 40% and 40% respectively at end of treatment. Conclusion: Thus, X-pert MTB/RIF is an important tool than sputum smear and AFB culture in monitoring the outcome of cavitary pulmonary tuberculosis

Fosfomycin: A Substitute in Therapeutic Options for Extended Spectrum Beta-lactamase Producing Uropathogens

Background: The emergence of antibiotic resistance among pathogens causing urinary tract infections (UTI) has made treatment options limited. The use of fosfomycin along with other drug combination can significantly address this problem. Our study aimed to identify the rate of resistance among uropathogens and their susceptibility patterns to fosfomycin along with other antibacterial agents. Methods: The retrospective study was conducted at Jinnah Sindh Medical University in collaboration with Dr. Tahir Laboratory, Karachi. A total of 146 urine samples were included which were processed for antibacterial susceptibility testing by Kirby-Bauer disk diffusion method and rate of resistance for antibacterial agents especially fosfomycin were recorded. The statistical analysis was performed by using Chi squared tests and p>0.05 was considered statistically significant. Results: The study reported lowest rate of resistance for fosfomycin among Escherichia coli 3(5.3%), Klebsiella pneumoniae 7(14%) and Pseudomonas aeruginosa 9(22.5%) in comparison with ampicillin, which showed resistance in 43(76.8%), 41(82%) and 39(97.5%) cases of E. coli, K. pneumoniae and P. aeruginosa respectively. The subgroup carbapenem resistant Enterobacteriaceae (CRE) and extended spectrum β-lactamases (ESBLs) producers were seen noticeably high in P. aeruginosa. Overall, the female to male ratio was 1.4:1 (87/59), showing female preponderance (p=0.02). A majority of patients belonged to adult age group (61.6%) followed by senior adults (23.2%, p=0.05). Conclusion: High levels of resistance to commonly used antibiotics were observed. The increasing rate of resistance among Enterobacteriaceae to cephalosporin and ampicillin is an alarming situation. In this context, fosfomycin is an interesting alternative option in treatment of complicated and uncomplicated urinary tract infections. Keywords: Antibiotic Resistance; Enterobacteriaceae; Extended Spectrum Beta Lactamase; Fosfomycin; Urinary Tract Infection

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The Effect of Alendronate on Proteome of Hepatocellular Carcinoma Cell Lines

Cancer is a life threatening disorder effecting 11 million people worldwide annually. Among various types of cancers, Hepatocellular carcinoma (HCC) has a higher rate of mortality and is the fifth leading cause of cancer related deaths around the world. Many chemotherapeutic drugs have been used for the treatment of HCC with many side effects. These drugs are inhibitors of different cell regulatory pathways. Mevalonate (MVA) pathway is an important cellular cascade vital for cell growth. A variety of inhibitors of MVA pathway have been reported for their anticancerous activity. Bisphosphonates (BPs) are members of a family involved in the treatment of skeletal complications. In recent years, their anticancer potential has been highlighted. Current study focuses on exploring the effects of alendronate (ALN), a nitrogen containing BP, on hepatocellular carcinoma cell line using genomic and proteomics approach. Our results identified ten differentially expressed proteins, of which five were up regulated and five were down regulated in ALN treated cells. Furthermore, we also performed gene expression analysis in treated and control cell lines. The study may help in understanding the molecular mechanism involved in antitumor activity of ALN, identification of possible novel drug targets, and designing new therapeutic strategies for HCC

Formal Modeling and Analysis of Air Traffic Control System Using Petri Nets

Air traffic control (ATC) system in airports is one of the most complex systems due to the huge number of requirements in the framework of air traffic management. The incessant increase in air traffic over the past few decades, so it is more challenging for ATC System to manage flow of the aircraft using one runway. To organize and expedite the flow ofair traffic, we proposed a formal model of ATC using two runways by Hierarchical timed Color Petri Net. HTCPN is appropriate to present complex reactive system. ATC assign landing and taking over runways according to the first-come-first-served (FCFS) approach. CPN tool is used for simulation and analysis of proposed model. Space state analysis isperformed to check the behavior of model like boundedness, liveness and dead lock properties etc. Performance analysis is conducted to check accuracy of model

Differential Protein Expression in Response to Varlitinib Treatment in Oral Cancer Cell Line: an In Vitro Therapeutic Approach

Epidermal growth factor receptor (EGFR) is the most frequently overexpressed receptor histologically exhibited by oral squamous cell carcinoma (OSCC) patients. Aberrated EGFR signaling may lead to recurrence and metastasis, thus laying the foundation of targeted therapy. Deactivating EGFR is likely to prevent downstream signaling thus resulting in apoptosis. Tyrosine kinase inhibitors (TKIs) have come into play to revert aggressiveness of OSCC. We exploited comparative proteomic analyses based on anti‐EGFR potential of varlitinib, using cellular proteomes from treated and untreated groups of oral cancer cells to identify protein players functional during oral carcinogenesis. Following separation by two-dimensional electrophoresis, differentially expressed cellular proteins (varlitinib-treated and untreated cells) were analyzed and later identified using QTOF mass spectrometer. In silico analysis for protein–protein interaction was carried out using STRING. Six differentially expressed proteins were identified as binding immunoglobulin protein (BiP), heat shock protein 7 C (HSP7C), protein disulfide isomerase 1 A (PDIA1), vimentin (VIME), keratin type I cytoskeletal 14 (K1C14), and β-Actin (ACTB). Relative expression of five proteins was found to be downregulated upon varlitinib treatment, whereas only K1C14 was upregulated in treated cells compared to control. Protein network analysis depicts the interaction between BiP, PDIA1, VIME, etc. indicating their role in oral carcinogenesis. Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and β-Actin as complementary/prognostic markers of OSCC