Ratio of height to thyromental distance: a comparison with mallampati and upper lip bite test for predicting difficult intubation in Pakistani population.

OBJECTIVE: To compare the accuracy of three diagnostic tests in predicting difficult laryngoscopy using Cormack and Lehane grade as the gold standard. METHODS: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from August 2014 to August 2015, and comprised patients who required endotracheal intubation for elective surgical procedures. The primary investigator used ratio of height to thyromental distance, upper lip bite test and the modified Mallampati test for assessing the airway correlated with laryngoscopic view based on Cormack and Lehane grading. Data was analysed using SPSS 19. RESULTS: Of the 383 patients, 59(15.4%) were classified as difficult cases of laryngoscopy. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ratio of height to thyromental distance were 84.7%, 90.1%, 60.9%, 97%, 89.3%; and those the corresponding values for the upper lip bite test were 83.1%, 89.2%, 58.3%, 96.7% and 88.3%. The values for the modified Mallampati test were 30.5%, 84.3%, 26.1%, 86.9% and 79.9% respectively. The area under receiver-operating characteristic curve for the first two tests was significantly more than for the modified Mallampati test (p<0.01). CONCLUSIONS: RHTMD and ULBT both are acceptable alternatives for prediction of difficult laryngoscopy as a simple, single bed-side test.

Neoteric Approach of Fluoxetine Laden Orodispersible Film for Non-compliant Pediatric Patients of Selective Mutism and Obsessive-compulsive Disorder.

OBJECTIVES: The objective of this research was to fabricate, characterize, and optimize fluoxetine laden orodispersible film (ODF), in enhancing dosage forms options for the pediatric population suffering from incapacitating psychotic disorders of selective mutism and obsessive-compulsive disorder, which will be ultimately beneficial in enhancing compliance factor and the quality of pharmacotherapy. MATERIALS AND METHODS: Solvent casting technique was used to formulate the ODF formed by natural hydrophilic polymers matrix of hydroxypropyl methylcellulose E15 and pullulan. Propylene glycol as plasticizing agent imparted satisfactory tenacity and flexibility to ODFs. Fourier transform infrared spectroscopy studies were performed to investigate any potential compatibility, and the results revealed no potential interaction between fluoxetine and excipients. Developed ODFs were evaluated for physicochemical properties, content uniformity, in vitro disintegration time, and in vitro dissolution time studies. Results: The experimental data. RESULTS: The experimental data suggested that different polymer concentrations had a complex effect on content uniformity, in vitro disintegration time, and cumulative percentage drug release from the ODFs. TF7 was the most optimized formulation with a disintegration time of 10.66 sec and 99.37% drug release within 3 min. Additionally, the most optimized fluoxetine ODF was submitted to a Universal Testing Machine for tensile strength and percentage elongation determination. It was also further evaluated by thermogravimetric analysis, scanning electron microscopy and X-ray diffraction. CONCLUSION: Fluoxetine ODFs of good pharmaceutical quality can be prepared on a small scale. Therefore, the perspective of using fluoxetine ODFs for individualized pharmacotherapy to ameliorate the compliance issues in selective mutism and OCD pediatric patients can be considered.

Future Smart Connected Communities to Fight COVID-19 Outbreak.

Internet of Things (IoT) has grown rapidly in the last decade and continues to develop in terms of dimension and complexity, offering a wide range of devices to support a diverse set of applications. With ubiquitous Internet, connected sensors and actuators, networking and communication technology along with artificial intelligence (AI), smart cyber-physical systems (CPS) provide services rendering assistance and convenience to humans in their daily lives. However, the recent outbreak of COVID-19 (also known as coronavirus) pandemic has exposed and highlighted the limitations of contemporary technological deployments especially to contain the widespread of this disease. IoT and smart connected technologies together with data-driven applications can play a crucial role not only in the prevention, mitigation, or continuous remote monitoring of patients, but also enable prompt enforcement of guidelines, rules, and administrative orders to contain such future outbreaks. In this paper, we envision an IoT and data-supported connected ecosystem designed for intelligent monitoring, pro-active prevention and control, and mitigation of COVID-19 and similar epidemics. We propose a gamut of synergistic applications and technology systems for various smart infrastructures including E-Health, smart home, supply chain management, transportation, and city, which will work in convergence to develop 'pandemic-proof' future smart communities. We also present a generalized cloud-enabled IoT implementation framework along with scientific solutions, which can be adapted and extended to deploy smart connected ecosystem scenarios using widely used Amazon Web Services (AWS) cloud infrastructures. In addition, we also implement an E-Health RPM use case scenario to demonstrate the need and practicality for smart connected communities. Finally, we highlight challenges and research directions that need thoughtful consideration and across the board cooperation among stakeholders to build resilient communities against future pandemics.

Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development.

Breast cancer is a complex disease with multiple factors involved in its pathophysiological development. genetic mutations of BRCA1, BRCA2 and p53 are among the most well-studied factors. The role of other genetic factors like altered expression profiles, SNPs in the regulatory regions of different genes or epigenetic factors like promoter methylation and histone modifications are also well studied but no solid understanding is available on distinct key players triggering malignancy in breast cancer, (Phosphatase and tensin homolog) PTEN is known to be a crucial tumor suppressor as it has been reported to be missing or abnormally expressed in many cancer cells. Here in this were studied how PTEN is expressed in malignant and benign cancer cells by investigating its expression profile and cellular location using Immuno-fluorescence microscopy. At the same time, quantitative studies of the circulatory mi-RNAs related to the downregulation of PTEN, namely mir-21 and mir-155 have studied also. Sixty biopsy samples, forty were diagnosed to be malignant and twenty were benign. It has been found that PTEN is normally expressed in benign samples and its normally localized in the cell membrane, while in malignant samples the expression level of PTEN is lower or absent and it is translocated to the cytoplasm. Interestingly the quantitative expression of circulatory mir-21 and mir-155 in the blood plasma of the corresponding patients showed a related pattern with higher expression in malignant samples, therefore can it's clear that PTEN is in the cross-talk of genetics and epigenetic regulation in regard of the development of malignant breast cancer. At the same time, this study confirms the importance of circulatory miRNAs as a biomarker for early breast cancer detection.

Coumarin derivatives as acetyl- and butyrylcholinestrase inhibitors: An in vitro, molecular docking, and molecular dynamics simulations study.

Alzheimer's disease is an irreversible and progressive brain disease that can cause problems with memory and thinking skills. It is characterized by loss of cognitive ability and severe behavioral abnormalities, and could lead to death. Cholinesterases (ChEs) play a crucial role in the control of cholinergic transmission, and subsequently, the acetylcholine level in the brain is upgraded by inhibition of ChEs. Coumarins have been shown to display potential cholinesterase inhibitory action, where the aromatic moiety has led to the design of new candidates that could inhibit Aß aggregation. Accordingly, the present work is an in vitro activity, along with docking and molecular dynamics (MD) simulation studies of synthesized coumarin derivatives, to explore the plausible binding mode of these compounds inside the cholinesterase enzymes. For this purpose, a series of previously prepared N1-(coumarin-7-yl) derivatives were screened in vitro for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. The assayed compounds exhibited moderate inhibitory activity against AChE, with IC50 values ranging from 42.5 ± 2.68 to 442 ± 3.30 µM. On the other hand, the studied compounds showed remarkable activity against BChE with IC50 values ranging from 2.0 ± 1.4 nM to 442 ± 3.30 µM. In order to better understand the ligand binding site interaction of compounds and the stability of protein-ligand complexes, a molecular docking with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases. We concluded that the tested coumarin derivatives are potential candidates as leads for potent and efficacious ChEs inhibitors.

Purification and Characterization of a Nonspecific Lipid Transfer Protein 1 (nsLTP1) from Ajwain (Trachyspermum ammi) Seeds.

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 is comprised of 91 amino acids, with eight conserved cysteine residues. The amino acid sequence based predicted three dimensional (3D) structure is composed of four α-helices stabilized by four disulfide bonds, and a long C-terminal tail. The predicted model was verified by using different computational tools; i.e. ERRAT, verify 3D web server, and PROCHECK. The docking of ajwain nsLTP1 with ligands; myristic acid (MYR), and oleic acid (OLE) was performed, and molecular dynamics (MD) simulation was used to validate the docking results. The findings suggested that amino acids; Leu11, Leu12, Ala55, Ala56, Val15, Tyr59, and Leu62 are pivotal for the binding of lipid molecules with ajwain nsLTP1.