Development of Ridge Ensemble Standardized Drought Index (RESDI) for improving drought characterization and future assessment.

Global warming upsets the environmental balance and leads to more frequent and severe climatic events. These extreme events include floods, droughts, and heatwaves. These widespread extreme events disrupt various sectors of ecosystems directly. However, among all these events, drought is one of the most prolonged climatic events that significantly destroys the ecosystem. Therefore, accurate and efficient assessment of droughts is necessary to mitigate their detrimental impacts. In recent years, several drought indices based on global climate models (GCMs) of Coupled Model Intercomparison Project Phase 6 (CMIP6) have been proposed to quantify and monitor droughts. However, each index has its advantages and limitations. As each index ensembles different models by using different statistical approaches, it is well known that the margin of error is always a part of statistics. Therefore, this study proposed a new drought index to reduce the uncertainty involved in the assessment of droughts. The proposed index named the Ridge Ensemble Standardized Drought Index (RESDI) is based on the innovative ensemble approach termed ridge parameters and distance-based weighting (RDW) scheme. And the development of this RDW scheme is based on two types of methods i.e., ridge regression and divergence-based method. In this research, we ensemble 18 different GCMs of CMIP6 using the RDW scheme. A comparative analysis of the RDW scheme is performed against the simple model average (SMA) and Bayesian model averaging (BMA) schemes at 32 locations on the Tibetan plateau. The comparison revealed that RDW has less mean absolute error (MAE) and root-mean-square error (RMSE). Therefore, the developed RESDI based on RDW is used to project drought properties under three distinct shared socioeconomic pathway (SSP) scenarios: SSP1-2.6, SSP2-4.5, and SSP5-8.5, across seven different time scales (1, 3, 7, 9, 12, 24, and 48). The projected data is then standardized by using the K-components Gaussian mixture model (K-CGMM). In addition, the study employs steady-state probabilities (SSPs) to determine the long-term behavior of drought. The outcome of this research shows that "normal drought (ND)" has the highest probability of occurrence under all scenarios and time scales.

Rectal Administration of Celecoxib Liquid Suppositories with Enhanced Bioavailability and Safety in Rats.

BACKGROUND: Celecoxib is generally used for the treatment of rheumatoid arthritis, however its poor bioavailability and cytotoxicity in pure form have reduced its therapeutic efficacy. This study aims to develop celecoxib liquid suppositories with improved bioavailability and reduced toxicity. METHODS: The celecoxib liquid suppositories were prepared by thoroughly mixing celecoxib, poloxamer 188 and poloxamer 407, and tween-20, respectively used as drug, polymers and surfactant, in triple distilled water using cold technique. The developed liquid suppositories were characterized in terms of their gelation temperature, gelation time, and gel strength. Moreover, the muco-adhesive force was determined for the suppositories. The release behavior of the liquid suppositories was investigated in distilled water and compared with drug suspension. Furthermore, pharmacokinetics and morphological studies were carried out in rats after rectal administration of the celecoxib liquid suppository compared with drug suspension. RESULTS: Poloxamer 188 and Tween-20 concentrations have significantly reduced the gelation temperature and time; however, the gel strength and bio-adhesive force were significantly enhanced. The concentration of celecoxib has no significant effect on the properties of liquid suppositories. A significantly enhanced and potentially sustained drug release was observed from the celecoxib liquid suppositories as compared with the drug suspension. The optimized formulation was easy to administer rectally because it quickly forms gel upon insertion into the body due to a suitable gelation temperature of about 31.7 °C. After rectal administration in rats, the celecoxib liquid suppository gave a significantly increased pharmacokinetic profile including enhanced plasma concentration and 9.7 fold improved area under the curve (AUC) compared to the drug suspension. Additionally, the morphology study exhibited no toxicity to the rectal tissue, no signs of irritation, or injury after the application of suppository. However, severe rectal tissue toxicity and irritation was observed in the suspension treated rectum. CONCLUSION: It can be concluded that the liquid suppository system may significantly enhance the solubilization and bio-availability of sparingly water-soluble drugs as evident in the case of celecoxib with no toxicity at the site of application.

Studies on antioxidant, anti-diabetic and GC-MS analyses of methanol extract of Aristolochia bracteolata root bark.

Aristolochia bracteolatais utilized in confronting multiple and complicated disease conditions such as cancer, lung inflammation, dysentery, syphilis, gonorrhea, arthritis, skindiseases, snake bite and oxidative stress relating to humans due to their acceptability, affordability and proximity. This investigation seeks to determine the antioxidant and anti-diabetic effects of methanol extract of A. bracteolate root bark in vitro. The phytochemical screening, antioxidant, and enzymes inhibitory (alpha-amylase and alpha-glucosidase) properties of root bark extract were evaluated by standard procedures. The methanol extract indicated the presence of diverse phytochemicals (tannins, saponins, flavonoids, alkaloids, phenols, glycosides and terpenoids) and contained a remarkable amount of saponins (8.20±0.03%), phenols (6.82±0.01%), alkaloids (4.71±0.03%) and flavonoids (3.50±0.12%). The extract showed not only strong antioxidant properties against DPPH, FRAP and TBARS radicals with IC50 value of 57.87, 54.64 and 47.54 mg/ml, respectively but also anti-diabetic activity by inhibiting alpha-amylase (IC50=53.70 mg/ml) and alpha-glucosidase (IC50=49.18 mg/ml). GC-MS chromatogram identified a diverse array of active metabolites in the methanol extract of A. bracteolate root bark. This study suggested that the methanol extract of A. bracteolate root bark possessed anti-oxidative and anti-diabetic activities.

In Vitro, Ex Vivo, and In Vivo Evaluation of Nanoparticle-Based Topical Formulation Against Candida albicans Infection.

Ketoconazole is commonly used in the treatment of topical fungal infections. The therapy requires frequent application for several weeks. Systemic side effects, allergic reactions, and prolonged treatment are often associated with non-compliance and therapy failure. Hence, we developed an optimized topical antifungal gel that can prolong the release of drug, reduce systemic absorption, enhance its therapeutic effect, and improve patient compliance. Ketoconazole-loaded PLGA nanoparticles were prepared by the emulsion/solvent evaporation method and were characterized with respect to colloidal properties, surface morphology, and drug entrapment efficiency. The optimized ketoconazole-loaded PLGA nanoparticles and commercially available silver nanoparticles were incorporated into a Carbopol 934P-NF gel base. This arrangement was characterized and compared with commercially available 2% ketoconazole cream to assess physical characteristics of the gel, in vitro drug release, ex vivo skin permeation and retention, and in vivo studies on Wister male albino rats. The results showed that polymeric PLGA nanoparticles were very effective in extending the release of ketoconazole in our optimized formulation. Nanoparticles were smooth, spherical in shape, and below 200 nm in size which is consistent with the data obtained from light scattering and SEM images. The ex vivo data showed that our gel formulation could strongly reduce drug permeation through the skin, and more than 60% of the drug was retained on the upper surface of the skin in contrast to 38.42% of the commercial cream. The in vivo studies showed that gel formulation could effectively treat the infection. This study demonstrates that our topical gel could be effective in sustaining the release of drug and suggests its potential use as a possible strategy to combat antifungal-resistant Candida albicans.

Tannic acid inhibits lipopolysaccharide-induced cognitive impairment in adult mice by targeting multiple pathological features.

Tannic acid (TA) is a natural compound present abundantly in fruit such as grapes and green tea. In this study, we have evaluated the therapeutic efficacy of TA against Lipopolysaccharide (LPS)-induced oxidative stress-mediated memory impairment, neuroinflammation, insulin signaling impairment, and Amyloid Beta (Aß) deposition in adult male mice. The LPS was administered once per week and TA twice a week to adult male mice for three months consecutively. Behavioral studies were performed using different behavioral models such as balance beam, novel object recognition (NOR), Morris water maze (MWM), and Y-maze tests. The protein expression of different mediators such as TNF-α, p-JNK, pIRS636, BACE1, APP, and Aß was evaluated through western blot and immunofluorescence staining techniques. Biochemical assays were carried out to assess the antioxidant activities of TA. The computational study was conducted to predict the binding mode of TA with target sites of TNF-α. Behavioral studies showed that the TA-treated mice exhibited gradual memory improvement. TA significantly inhibited BACE1 activity and reduced production and accumulation of Aß in the hippocampus of mice brains. Moreover, the TA significantly inhibited LPS-induced ROS production and enhanced the glutathione levels. Furthermore, we have shown via the computational method for the first time that TA inhibits LPS-triggered TNF-á½° and its downstream signaling to reduce AD pathology including memory impairment, neuroinflammation, insulin signaling impairment, and Aß deposition in adult mice. Taken together our current study demonstrates that TA is a potential candidate for the abrogation of LPS-induced neurotoxicity and AD pathology in rodent's models.

Comparative molecular docking and molecular-dynamic simulation of wild-type- and mutant carboxylesterase with BTA-hydrolase for enhanced binding to plastic.

According to the literature review, microbial degradation of polyethylene terephthalate by PETases has been detected effective and eco-friendly. However, the number of microorganisms capable of such feats is limited with some undesirable bioprospecting results. BTA-hydrolase has been already reported capable of degrading polyethylene terephthalate. Therefore, mutation by in silico site-directed mutagenesis means to introduce current isomer of PETase for polyethylene terephthalate degradative capability as a better approach to resolve this issue. This study aimed to use in silico site-directed mutagenesis to convert a carboxylesterase from Archaeoglobus fulgidus to BTA-hydrolase from Thermobifida fusca by replacing six amino acids in specific locations. This work was followed by molecular docking analysis with polyethylene terephthalate and polypropylene to compare their interactions. The best-docked enzyme-substrate complex was further subjected to molecular dynamics simulation to gauge the binding quality of the BTA-hydrolase, wild-type and mutant-carboxylesterase with only polyethylene terephthalate as a substrate. Results of molecular docking revealed lowest binding energy for the wild-type carboxylesterase-polypropylene complex (-7.5 kcal/mol). The root-mean-square deviation value was observed stable for BTA-hydrolase. Meanwhile, root-mean-square fluctuation was assessed with higher fluctuation for the mutated residue Lys178. Consequently, the Rg value for BTA-hydrolase-ligand complex (∼1.68 nm) was the lowest compared to the mutant and wild-type carboxylesterase. The collective data conveyed that mutations imparted a minimal change in the ability of the mutant carboxylesterase to bind to polyethylene terephthalate.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Prediction of microsleeps using pairwise joint entropy and mutual information between EEG channels.

Microsleeps are involuntary and brief instances of complete loss of responsiveness, typically of 0.5-15 s duration. They adversely affect performance in extended attention-driven jobs and can be fatal. Our aim was to predict microsleeps from 16 channel EEG signals. Two information theoretic concepts - pairwise joint entropy and mutual information - were independently used to continuously extract features from EEG signals. k-nearest neighbor (kNN) with k = 3 was used to calculate both joint entropy and mutual information. Highly correlated features were discarded and the rest were ranked using Fisher score followed by an average of 3-fold cross-validation area under the curve of the receiver operating characteristic (AUCROC). Leave-one-out method (LOOM) was performed to test the performance of microsleep prediction system on independent data. The best prediction for 0.25 s ahead was AUCROC, sensitivity, precision, geometric mean (GM), and φ of 0.93, 0.68, 0.33, 0.75, and 0.38 respectively with joint entropy using single linear discriminant analysis (LDA) classifier.

Antibacterial activity of Phyllantus emblica, Coriandrum sativum, Culinaris medic, Lawsonia alba and Cucumis sativus.

Present study deals with the demonstration of the antibacterial activity of very common medicinal plants of Pakistani origin i.e., Phyllantus emblica, Coriandrum sativum, Culinaris medic, Lawsonia alba and Cucumis sativus. The extracts were prepared in crude form by the use of hydro-alcoholic solution and were screened for antibacterial activity against various bacterial species by disk diffusion method. Assay was performed using clinical isolates of B. cereus, S. aureus, P. aeruginosa and E. coli. Crude extract of Phyllantus emblica fruit exhibited strong activity against standard cultures of all studied bacteria. Lawsonia alba showed good activity against standard cultures of all the used microorganisms. Coriandrum sativum was effective only against Bacillus cereus, while Cucumis sativus and Culinaris medic showed poor activity against Pseudomonas aeruginosa only. Hence, Phyllantus emblica exhibited strong antibacterial activity against a wide range of bacteria it means that Phyllantus emblica extract contains some compounds which have broad spectrum of bactericidal activity.

Evaluation of self-medication amongst university students in Abbottabad, Pakistan; prevalence, attitude and causes.

Self-medication is a serious issue in most parts of the world. This study aims to evaluate self-medication among university students of Abbottabad, Pakistan. This cross-sectional survey study was carried out in COMSATS Institute of Information Technology, Abbottabad during December 1 - December 31,2011. A sample of 275 students was selected for the study using convenience method of sampling. Data were managed and analyzed via SPSS version 16.0. Inferences were drawn using Z-test Out of 268 respondents (male = 61.6%, female = 38.6%), 138 were non-health professional students whereas 130 were health professional students. The prevalence of self-medication was 95.5%. Most common factor (45.7%) responsible for self-medication was "low severity of disease". Most common symptom (50.8%) that caused self-medication and stocking of medicines was "storage of medicines for multi purposes". Some respondents (22.7%) got addicted due to self-medication. Most of the students trust in allopathic medicines system. High prevalence of self-medication can be controlled through regulatory authorities, mass education and availability of health facilities.

Physico-chemical comparison of famotidine tablets prepared via dry granulation and direct compression techniques.

Famotidine is generally employed for the treatment of gastric ulcer. The present study was conducted to fabricate famotidine tablets using various diluents. The binder was incorporated to the formulations in different proportions. Both the dry granulation and direct compression techniques were employed to develop the tablets. Physical evaluation of tablets i.e. tablets hardness, friability, weight variation, thickness and diameter was determined. In vitro dissolution studies of the prepared tablets were carried out for 60 min using the USP apparatus II and 900 ml 0.1 M HCl stirred at 37 ± 0.5°C with a speed of 50 rpm. Physical analysis of tablets prepared via direct compression showed satisfactory results regarding the weight variation, hardness and friability, since their respective values were within the BP limits. All the prepared famotidine tablets exhibited diffusion based mode of drug release. 100% release of drug occurred in less than 60 min. The drug release from all the formulated tablets has elaborated the involvement of diffusion (Higuchian drug release). This comparative study exhibited that physical parameters of tablets are affected by the technique of tabletting.

Tube thorocostomy: management and outcome in patients with penetrating chest trauma.

BACKGROUND: Penetrating chest trauma is common in this part of the world due to present situation in tribal areas. The first line of management after resuscitation in these patients is tube thoracostomy combined with analgesia and incentive spirometry. After tube thoracostomy following surgery or trauma there are two schools of thought one favours application of continuous low pressure suction to the chest tubes beyond the water seal while other are against it. We studied the application of continuous low pressure suction in patients with penetrating chest trauma. This Randomized clinical controlled trial was conducted in the department of thoracic surgery Post Graduate Medical Institute Lady Reading Hospital Peshawar from July 2007 to March 2008. The objectives of study were to evaluate the effectiveness of continuous low pressure suction in patients with penetrating chest trauma for evacuation of blood, expansion of lung and prevention of clotted Haemothorax. METHODS: One hundred patients who underwent tube thoracostomy after penetrating chest trauma from fire arm injury or stab wounds were included in the study. Patients with multiple trauma, blunt chest trauma and those intubated for any pulmonary or pleural disease were excluded from the study. After resuscitation, detailed examination and necessary investigations patients were randomized to two groups. Group I included patients who had continuous low pressure suction applied to their chest drains. Group II included those patients whose chest drains were placed on water seal only. Lung expansion development of pneumothorax or clotted Haemothorax, time to removal of chest drain and hospital stay was noted in each group. RESULTS: There were fifty patients in each group. The two groups were not significantly different from each other regarding age, sex, pre-intubation haemoglobin and pre intubation nutritional status. Full lung expansion was achieved in forty six (92%) patients in group I and thirty seven (74%) in group II. Partial lung expansion or pneumothorax was present in three (60%) in group I and 10 (20%) in group II. One patient in group I and three (6%) patients in group II had no response. The mean time to removal of chest drains were 8.2 +/- 3.14 days in group I and 12.6 +/- 4.20 days in group II. The length of hospital stay was 7.2 +/- 2.07 days and 12.4 +/- 3.63 days in group I and II respectively. Clotted Haemothorax requiring surgery developed in three (6%) patients in group I and 8 (16%) patients in group II. CONCLUSION: Placing chest tubes on continuous low pressure suction after penetrating chest trauma helps evacuation of blood, expansion of lung and prevents the development of clotted Haemothorax. It also reduces the time to removal of chest drains, the hospital stay and the chances of surgery for clotted Haemothorax or Empyema.

Effect of menopause on serum HDL-cholesterol level.

BACKGROUND: There is a marked difference in the risk of coronary heart disease between men and women of reproductive age but this gap closes with advancing age. It seems likely that some factors of reproductive physiology are responsible for this. The present study was designed to evaluate the difference in HDL Cholesterol level in premenopausal and postmenopausal women in relation with change of estradiol level. METHODS: Fifty premenopausal and 50 postmenopausal women were included in the study. Estradiol was estimated by radioimmuoassay while HDL-C was estimated by Kit method. RESULTS: There was a significant (p < 0.01) decrease in the HDL-C level of the postmenopausal women (46.72 +/- 1.009) as compared with premenopausal women (63.68 +/- 1.78). CONCLUSION: HDL-C is an independent risk factor for coronary heart disease. This study favours the view that decrease in estradiol level and associated decrease in HDL-C seen in postmenopausal women may be responsible for the increased risk of coronary heart disease after menopause.

Comparison of troponin T and enzyme levels in acute myocardial infarction and skeletal muscle injury.

BACKGROUND: The objective of this study was to compare the levels of troponin T and enzymes levels in myocardial infarction and skeletal muscle injury. METHODS: This study was carried out at Basic Medical Sciences Institute, JPMC Karachi, Pakistan. Ninety subjects were selected. Thirty controls, thirty patients suffering from myocardial infarction and thirty suffering from skeletal muscle injury were selected from National Institute of Cardiovascular Diseases. Creatine kinase, aspartate amino-transferase, lactate dehydrogenase and Troponin T were determined by kit methods. RESULTS: Troponin T level rises significantly (p < 0.01) in patients suffering from myocardial infarction. Creatine kinase (CK), CKMB, aspartate aminotransferase and lactate dehydrogenase levels rises significantly (p < 0.01) in both groups compared with controls. CONCLUSION: Troponin T is an early indicator of myocardial infarction and is superior to CKMB in diagnosis of myocardial injury. There is no increase in troponin T levels in skeletal muscle injury.