Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults

Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex-vivo StkP446–60-tetramer binding in HLA-DRB1*1501 adults. These StkP446–60-tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP446–60-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We found that ex-vivo pneumococcal-specific T cells were detectable in healthy adults and that they were enriched with cell surface markers associated with recent antigen exposure and later stages of antigen-driven differentiation. It is likely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynx and it is possible that they may be preventing subsequent colonisation and disease

Current options and therapeutic strategies for the management of cancer

The disease is thought to be a significant general medical problem in created and emerging nations. The high mortality related to particular kinds of illness (Lung, prostate, stomach, and colorectal) legitimizes a developing interest in the recognizable proof of new pharmacological specialists effective in malignant growth counteraction and treatment. A few strategies are accessible to treat disease like a medical procedure, chemotherapy, radiation treatment, immunotherapy, and monoclonal immunizer treatment. The decision of treatment relies on the area of the growth, grade of the cancer, the phase of the infection, and the overall condition of the patient. Plants are considered as the great wellspring of profoundly compelling traditional specialists for the therapy of many sorts of malignant growth. The restorative plants' phytochemical investigation has generally added to the disclosure of new anticancer medications. This article has been made to audit a few restorative plants utilized for the therapy of malignant growth and gives information about anticancer therapeutic plants, which are utilized by individuals in all around the Asian nations.

The Relationship between Knowledge Management Practices and Organizational Performance: Evidence from Banking Sector of Southern Punjab, Pakistan

The main objective of this study is to empirically investigate the relationship between knowledge management practices and organizational performance in the banking sector of districts of Punjab, Pakistan. Target population of the study was all the employees providing customer services of all banks located in the districts of Punjab province of Pakistan. Simple random sampling was used to select an appropriate and truly representative sample. Sample size of this research was 306 and out of 306 questionnaires, 291 were useful for the purpose of this research and hence making our response rate 95%. The reliability of data was tested by Cronbach’s alpha and regression analysis was used for testing of hypotheses. All the hypotheses of the study were accepted which stated that information technology, organizational elements and knowledge have positive relationship with organizational performance and further this relationship was statistically significant. This study has been conducted in the banking industry which bars to generalize the results of this research to other business settings. The findings of this kind of study are possibly useful to decision making bodies within the Banking services and it is also helpful for the government policy makers to develop policies for the better operations of banking sector with the aim of growing banking industry. This study makes a contribution in knowledge management literature by empirically investigating the impact of knowledge management practices on organizational performance

Co-inoculation with Rhizobium and plant growth promoting rhizobacteria (PGPR) for inducing salinity tolerance in mung bean under field condition of semi arid climate

Salinity stress severely affects the growth, nodulation and yield of mung bean (Vigna radiata L.). However, its growth can be improved under salinity stress by inoculation/co-inoculation with rhizobia and plant growth promoting rhizobacteria (PGPR) containing 1-Aminocyclopropane-1-carboxylic acid (ACC) deaminase enzyme. ACC-deaminase containing bacteria regulate the stress induced ethylene production by hydrolyzing the ACC (immediate precursor of ethylene) into ammonia and ketobutyric acid, thus improve plant growth by lowering the ethylene level. A study was conducted under salt affected field conditions where pre-isolated strains of Rhizobium and PGPR were used alone as well as in combination for mitigating the salinity stress on growth, nodulation and yield of mung bean by following the randomized complete block design (RCBD). The data were recorded and analyzed statistically to see the difference among treatments

Doe guided chitosan based nano-ophthalmic preparation against fungal keratitis

A recent upsurge in ocular infections is a pointer towards an enhanced prevalence of ophthalmic disorders, posing challenges for researchers globally. The caveats of conventional therapeutics demand a specifically designed Ocular Drug Delivery System (ODDS) and hence the primary objective of the present work is a fabrication of a Design of Expert (DoE) guided Chitosan based Antifungal loaded Nanoparticles (CANs), as a locoregionally effective eye formulation/drops for fungal keratitis therapy. The purported formulation was prepared using High-Pressure Homogenisation technique and was critically characterized on various parameters to check their suitability as an ODDS. The optimized formulation has fruitfully yielded irregularly spherical particles in up to a size of 200 nm and a Poly-dispersity Index (PDI) of less than 0.2 nm. The optimised formulation has further showcased a high mucoadhesion capacity thereby, suggesting the greater retention of CANs on the mucous membrane of an eye with low ocular irritancy as highlighted using HET-CAM (Hen's Egg Chorioallantoic Membrane) test. The in-vitro drug release study across a dialysis membrane has indicated both diffusion as swelling controlled release pattern for an optimized formulation. The ex-vivo corneal permeation study on goat corneal tissues using a Franz-Diffusion cell also has indicated a steady increase in the permeation of drug with time for an optimized formulation. Further, the optimised formulation was found to be non-irritant and ocular safe in ex-vivo transcorneal toxicity studies on goat corneal tissues. In conclusion, the designing of a proposed nanosized formulation, offers a promising step towards the management of external ocular diseases with a positive attributes of high patient compliance, controlled drug delivery, prolonged drug precorneal residence time and enhanced ocular bioavailability. The optimized CANs could be further exploited as a potential ODDS

Mathematical Modeling of Drug Release of Novel Extended-Release Formulations of Tizanidine Hydrochloride

Six extended-release formulations of tizanidine hydrochloride were prepared by direct compression technique using hydroxypropylmethylcellulose (HPMC) and ethylcellulose (EC). The drug release from these tablets was evaluated by analyzing the samples at 227 nm. Both model dependent and independent mathematical approaches were applied to investigate the extended release pattern and mechanism of tizanidine hydrochloride. About 87.8, 74.4, 85.1, 74.8, 70.8, and 56.2 % drug was released from F1 to F6 , respectively, in 12 h. Drug release kinetics indicated that drug release was best explained by Higuchi equation. The values of ‘n’ from Korsmeyer-Peppas model (0.45 to 0.89) supported anomalous or nonFickian diffusion in first five formulations, whereas last formulation (F6 ) with ‘n’ greater than 0.89 presented case-II relaxation or super case transport-II. In model independent approach, the values of first five formulations lies between 50 and 100, because of insignificant differences in their drug release whereas F6 behaved differently. A retarding effect was observed with both of polymers depending upon their quantity. In F3 and F5 less retarding effect was observed than F2 and F5 because HPMC is hydrophilic and EC is hydrophobic polymer. When EC quantity increased, a decrease in release profile of tizanidine hydrochloride was observed.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Classification of EEG Signals for Prediction of Epileptic Seizures

Epilepsy is a common brain disorder that causes patients to face multiple seizures in a single day. Around 65 million people are affected by epilepsy worldwide. Patients with focal epilepsy can be treated with surgery, whereas generalized epileptic seizures can be managed with medications. It has been noted that in more than 30% of cases, these medications fail to control epileptic seizures, resulting in accidents and limiting the patient’s life. Predicting epileptic seizures in such patients prior to the commencement of an oncoming seizure is critical so that the seizure can be treated with preventive medicines before it occurs. Electroencephalogram (EEG) signals of patients recorded to observe brain electrical activity during a seizure can be quite helpful in predicting seizures. Researchers have proposed methods that use machine and/or deep learning techniques to predict epileptic seizures using scalp EEG signals; however, prediction of seizures with increased accuracy is still a challenge. Therefore, we propose a three-step approach. It includes preprocessing of scalp EEG signals with PREP pipeline, which is a more sophisticated alternative to basic notch filtering. This method uses a regression-based technique to further enhance the SNR, with a combination of handcrafted, i.e., statistical features such as temporal mean, variance, and skewness, and automated features using CNN, followed by classification of interictal state and preictal state segments using LSTM to predict seizures. We train and validate our proposed technique on the CHB-MIT scalp EEG dataset and achieve accuracy of 94%, sensitivity of 93.8% , and 91.2% specificity. The proposed technique achieves better sensitivity and specificity than existing methods.publishedVersio

Resource potential of gas reservoirs in South Pakistan and adjacent Indian subcontinent revealed by post-stack inversion techniques

Seismic post-stack inversion facilitates the interpretation, mapping and quantification of hydrocarbon-bearing zones. This study estimates reservoir properties (i.e. acoustic impedance and porosity) by applying post-stack seismic inversion techniques to a gas prone reservoir in the Sawan area, Southern Indus Basin, Pakistan. In this particular study, model-based and sparse-spike inversion algorithms are successfully applied on 3D seismic and wireline log data to predict reservoir character in the Lower Goru Formation (C-sand interval). Our results suggest that model-based post-stack seismic inversion provides more reasonable estimates (i.e. returning detailed spatial variations) for acoustic impedance and porosity when compared to sparse-spike inversion algorithms. The calibration of these estimates with petrophysical data from wireline log data indicates an appropriate agreement amongst them. Importantly, the results obtained in our case study can be applied to similar basins in Asia with 'tight' oil and 'tight' gas filling sand-shale intercalations with different thickness and areal distributions

Resource potential of gas reservoirs in South Pakistan and adjacent Indian subcontinent revealed by post-stack inversion techniques

Seismic post-stack inversion facilitates the interpretation, mapping and quantification of hydrocarbon-bearing zones. This study estimates reservoir properties (i.e. acoustic impedance and porosity) by applying post-stack seismic inversion techniques to a gas prone reservoir in the Sawan area, Southern Indus Basin, Pakistan. In this particular study, model-based and sparse-spike inversion algorithms are successfully applied on 3D seismic and wireline log data to predict reservoir character in the Lower Goru Formation (C-sand interval). Our results suggest that model-based post-stack seismic inversion provides more reasonable estimates (i.e. returning detailed spatial variations) for acoustic impedance and porosity when compared to sparse-spike inversion algorithms. The calibration of these estimates with petrophysical data from wireline log data indicates an appropriate agreement amongst them. Importantly, the results obtained in our case study can be applied to similar basins in Asia with 'tight' oil and 'tight' gas filling sand-shale intercalations with different thickness and areal distributions

Carbapenem Resistance: Mechanisms and Drivers of Global Menace

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace