A Systematic Critical Review of Clinical Pharmacokinetics of Torasemide.

PURPOSE: Torasemide is a potassium-sparing loop diuretic used to treat fluid retention associated with congestive heart failure and kidney and hepatic diseases. This systematic review was conducted to combine all accessible data on the pharmacokinetics (PK) of torasemide in healthy and diseased populations, which may help clinicians avert adverse drug reactions and determine the correct dosage regimen. METHODS: Four databases were systematically searched to screen for studies associated with the PK of torasemide, and 21 studies met the eligibility criteria. The review protocol was registered in the PROSPERO database (CRD42023390178). RESULTS: A decrease in maximum plasma concentration (C max ) was observed for torasemide after administration of the prolonged-release formulation in comparison to that after administration of the immediate-release formulation, that is, 1.12 ± 0.17 versus 1.6 ± 0.2 mcg/mL. After administering an oral dose of torasemide, a 2-fold increase in the area under the concentration-time curve (AUC) was reported in patients with congestive heart failure compared with the healthy population. Moreover, the patients with renal failure (clearance < 30 mL/min) showed an increase in value of AUC 0-∞ that is, 42.9 versus 8.091 mcg.h -1 .mL -1 compared with healthy subjects. In addition, some studies have reported interactions with different drugs, in which irbesartan showed a slight increase in the AUC 0-∞ of torasemide, whereas losartan and empagliflozin did not. CONCLUSIONS: The current review summarizes all available PK parameters of torasemide that may be beneficial for avoiding drug-drug interactions in subjects with renal and hepatic dysfunction and for predicting doses in patients with different diseases.

Clinical pharmacokinetics of nebivolol: a systematic review.

Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC0-∞) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (Cmax) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC0-∞ of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher Cmax, AUC0-∞ and half-life (t1/2) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.

Clinical pharmacokinetics of cefixime: a systematic review.

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration (Cmax), area under the curve (AUC), clearance (CL), and time to reach Cmax (tmax). A dose-dependent increase in AUC and Cmax of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Effects of transport-carbon intensity, transportation, and economic complexity on environmental and health expenditures.

Health and the environment are complex components of the countries, influenced by several factors, especially transport, and economics. Thus, this paper assesses the role of transportation and economic complexity in the environment and public health for the Organization for Economic Co-operation Development (OECD) countries from 2001 to 2020. This study also focuses on the relationship between transport and economic complexity with environmental and healthcare expenditures. Precisely, transport and economic activities stimulate healthcare expenditures through multiple channels. The current study employs the STIRPAT model to investigate the association with transportation, economic complexity, transport-carbon intensity, and healthcare expenditure. Besides, the current research confirms the plausible cross-sectional dependency across countries, and it adopts a second-generation technique. Analytical findings suggest that transportation-carbon intensity is positively and significantly associated with healthcare expenditures. Healthcare and transport-household expenditures increase transport-carbon intensity (TCI) by 75% and 45%, respectively, in the long run. In the contrast, TCI and transport-household expenditures have also a remarkable impact on healthcare expenditures and are estimated approximately 95% in the long run. Moreover, economic growth also upsurges TCI and healthcare expenditures through multiple economic activities. Besides, transport-household expenditures (THE) drastically impact transport-carbon intensity and healthcare expenditures (HEX) through passenger traffic (PTF). Diagnostic upshots unveil that the joint effect of THE and PTF increases TCI and HEX by 4 and 3%, respectively. Finally, findings recommend some policy implications and future research directions for the countries based on empirical outcomes. Countries should regulate economic activities to reduce transport carbon emissions.

A physiologically based pharmacokinetic model of cefepime to predict its pharmacokinetics in healthy, pediatric and disease populations.

The physiologically based pharmacokinetic modeling (PBPK) approach can predict drug pharmacokinetics (PK) by combining changes in blood flow and pathophysiological alterations for developing drug-disease models. Cefepime hydrochloride is a parenteral cephalosporin that is used to treat pneumonia, sepsis, and febrile neutropenia, among other things. The current study sought to identify the factors that impact cefepime pharmacokinetics (PK) following dosing in healthy, diseased (CKD and obese), and pediatric populations. For model construction and simulation, the modeling tool PK-SIM was utilized. Estimating cefepime PK following intravenous (IV) application in healthy subjects served as the primary step in the model-building procedure. The prediction of cefepime PK in chronic kidney disease (CKD) and obese populations were performed after the integration of the relevant pathophysiological changes. Visual predictive checks and a comparison of the observed and predicted values of the PK parameters were used to verify the developed model. The results of the PK parameters were consistent with the reported clinical data in healthy subjects. The developed PBPK model successfully predicted cefepime PK as observed from the ratio of the observed and predicted PK parameters as they were within a two-fold error range.

Leaving half the acetabulum in pelvic resections improves hip function. Is there a need to revisit conventional pelvic resections?

BACKGROUND: Conventional periacetabular pelvic resections are associated with poor functional outcomes. Resections through surgical corridors beyond the conventional margins may be helpful in retaining greater function without compromising the oncological margins. METHODS: The study included a retrospective review of 82 cases of pelvic resections for pelvic tumors. Outcomes of acetabulum preservation (Group A) were compared with complete acetabular resection (Group B). Also, we compared outcomes of Type I + half resections (Group 1) with Type I + II resections (Group 2), and Type III + half resections (Group 3) with Type II + III resections (Group 4). RESULTS: Group A (n = 44) had significantly better functional outcome than Group B (n = 38) with average MSTS93 score 22.3 versus 20.1 and average HHS 91.3 versus 82.5 (p < 0.001). Group 1 (n = 14) and Group 2 (n = 12) had similar functional outcomes (mean MSTS93 score 22.07 vs. 21.58 [p = 0.597] and mean HHS 90.37 vs. 86.51 [p = 0.205]). Group 3 (n = 11) had significantly better functional outcome than Group 4 (n = 17), with mean MSTS93 score 22.8 versus 19.7 (p < 0.001) and mean HHS 92.3 versus 80.1 (p < 0.001). Oncological outcomes were similar among the groups. CONCLUSION: Transacetabular pelvic resections provide functional benefit over conventional resections without compromising oncological margins. There is a need to revisit and revise the pelvic resection planes.

Clinical pharmacokinetics of nadolol: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of nadolol in humans and this can be beneficial for the clinicians in dosage adjustments. METHODS: Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review. RESULTS AND DISCUSSION: The area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of nadolol increased in a dose-dependent manner. The t½ of nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability. WHAT IS NEW AND CONCLUSION: Since, there is no previous report of a systematic review on the PK of nadolol, the current review encompasses all the relevant published articles on nadolol in humans. The analysis and understanding of PK parameters (AUC, Cmax , and t½) of nadolol may be helpful in the development and evaluation of PK models.

Effects of biochar, farm manure, and pressmud on mineral nutrients and cadmium availability to wheat (Triticum aestivum L.) in Cd-contaminated soil.

The contamination of agricultural soils with cadmium (Cd) is one of the serious worldwide concerns for food security. Biochar and organic manures have been known for enhancing plant growth and minimizing toxic trace element stress in plants. However, less is known about the effect of different organic amendments on Cd and uptake of essential nutrients by wheat. Thus, the effects of rice straw biochar (RSB), maize stalk biochar (MSB), farmyard manure (FYM), and pressmud (PRM) at a rate of 1% w/w were tested for Cd immobilization in soil and mineral nutrient availability to wheat crop grown in Cd-spiked soil (6.0 mg kg1 ). The amendments were added in Cd-spiked soil before 12 days of seed sowing and wheat plants were harvested after maturity (115 days after sowing). The findings revealed that the use of amendments improved the number of grains per spike, straw and grain yield of wheat relative to control treatment. The treatments minimized the Cd and enhanced the contents of zinc (Zn), nitrogen (N), phosphorus (P), and potassium (K) in the leaves and grain of the wheat plants. Cadmium concentrations decreased by 35, 38, 68, and 63% in wheat grain, and grain yield increased by 19, 31, 68, and 58% with the application of FYM, PRM, MSB, and RSB, respectively. Overall, the application of MSB was more efficient in decreasing Cd concentrations in leaf and grains of wheat as compared to other conventional organic amendments.

Does air pollution upsurge in megacities after Covid-19 lockdown? A spatial approach.

The current coronavirus (COVID-19) pandemic has a high spreading and fatality rate. To control the rapid spreading of the COVID-19 virus, the government of India imposed lockdown policies, which creates a unique opportunity to analyze the impact of lockdown on air quality in the two most populous cities of India, i.e., Delhi and Mumbai. To do this, the study employed a spatial approach to examine the concentration of seven criteria pollutants, i.e., PM2.5, PM10, NH3, CO, NO2, O3, and SO2, before, during, and after a lockdown in Delhi and Mumbai. Overall, around 42%, 50%, 21%, 37%, 53%, and 41% declines in PM2.5, PM10, NH3, CO, NO2, and SO2 were observed during the lockdown period as compared to previous years. On the other hand, a 2% increase in O3 concentration was observed. However, the study analyzed the National Air Quality Index (NAQI) for Delhi and Mumbai and found that lockdown does not improve the air quality in the long term period. Our key findings provide essential information to the cities' administration to develop rules and regulations to enhance air quality.

Knowledge, attitude, preventive practices and perceived barriers to screening about colorectal cancer among university students of newly merged district, Kpk, Pakistan - A cross-sectional study.

INTRODUCTION: Colorectal cancer is the third most common type of cancer in the world and in Pakistan it ranks at fifth position. The present study was conducted to evaluate the knowledge, attitude, preventive practices and perceived barriers to screening about colorectal cancer among university students. METHOD: A cross-sectional study was conducted after developing a self-administered questionnaire among the university students of newly merged districts of Kpk, Pakistan. RESULT: A total of 302 students (232 male and 70 female) participated in the study. The knowledge score of the participants regarding the risk factors and warning signs of colorectal cancer was 59.9% and 40%. More than 90% of the participants were of the view that colorectal cancer diagnosis at initial stages can improve treatment and around 80% were in favor of undergoing regular physical examination to avoid colorectal cancer. Only 37.7% of the participants had intentionally collected information about colorectal cancer. The percentage of participants who intentionally participated in educational activities related to colorectal cancer was 33.1%. Furthermore, only 24.4% of the participant had ever taken part in colorectal cancer screening. The barriers toward colorectal cancer screening were fear of finding colorectal cancer and the anxiety of screening procedures. However, around 32% of the participants had no knowledge about colorectal cancer screening. CONCLUSION: In view of the findings of this study, it can be suggested that community awareness programs that are focused towards screening of colorectal cancer may be initiated in the newly merged districts of Kpk, Pakistan. The implementation of such colorectal cancer screening program can help in its early detection and can potentially lower the associated mortality and morbidity risk with this disease.

Knowledge, Attitude, and Practices Toward COVID-19 in Primary Healthcare Providers: A Cross-Sectional Study from Three Tertiary Care Hospitals of Peshawar, Pakistan.

An online cross-sectional study was carried out to evaluate the knowledge, attitude, and practice about coronavirus disease 2019 (COVID-19) among primary health care providers (PHPs) at three tertiary care hospital, Peshawar, Pakistan. Data was collected via email and online social media platforms. Statistical package for social science (SPSS) version 25.0 was used for data analysis. Among the total participants (n = 114), 74 (66.7%) were male and 37 (33.3%) were female. The mean scores for knowledge, attitude and practice were 12.7 ± 0.89, 8.9 ± 4.1 and 7.3 ± 1.2, respectively. Most of the participants knew the term COVID-19 and its mode of transmission (90%), signs and symptoms (84%) and risk factors (72%) associated with it. Most of the participants agreed that COVID-19 can be transmitted through coughing and sneezing (74.3%) and 84.6% were in favor that COVID-19 can be prevented by adopting preventive measures. Around 68.8% of the participants disagreed with the use of antibiotics in the prevention of COVID-19. Ninety percent of the respondents were avoiding close contact with the people having cough and flu-like symptoms. Most PHPs had good knowledge, positive attitude and reasonable practices regarding COVID-19. Moreover, focused training programs for PHPs at the Government level can further improve their understanding of risks and preventive strategies related to COVID-19, which will help them to provide appropriate care to their patients as well as to protect themselves from this infection.

Association of breast cancer reporting delays and care intervals with tumor size in patients with advanced disease.

In Pakistan, breast cancer (BC) is frequently diagnosed with advanced disease. We aimed to examine the association of breast tumor size with reasons of reporting delays, care intervals in patients with advanced disease. This cross-sectional study enrolled 392 BC patients from tertiary care hospitals. Data were collected from August 2018-March 2019. Chi-square for significance and logistic regression for association were used. Patients between 31 and 45 years of age (51%), rural residents (39%), lower-class (88.4%), no family history (17.1%), at stage-IV (36%) and patient interval >90 days (70%, p = .034) presented with large tumor size (>5 cm). Tumor size was significantly associated with area of residence (p = .043), social-class (p = .027), family history (p = .004), smoking (p = .021), nipple discharge (p = .004), recurrence (p = .024), and metastasis (p = .007). Patient-interval was associated with poor knowledge (OR;4.3,p = .0001), influence of traditional healers (OR;2.3,p = .05), religion (OR;3.9,p = .0001), finances (OR;2.4,p = .045), and competing life priorities (OR;2.9,p = .026). In-adjusted linear regression model, area of residences, education, social-class, family-history, recurrence, cancer type, and patient interval (ß;0.110,p = .030) were found to be independent predictors of tumor size. In conclusion, education, family history, area of residence, social class, recurrence, cancer stage and patient interval, co-influenced by religion, finances, life priorities, traditional healers, and poor knowledge, were independent predictors of tumor size in BC patients.

Fabrication, Evaluation, In Vivo Pharmacokinetic and Toxicological Analysis of pH-Sensitive Eudragit S-100-Coated Hydrogel Beads: a Promising Strategy for Colon Targeting.

The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery.Graphical abstract.

Investigating the Role of Altered Systemic Albumin Concentration on the Disposition of Theophylline in Adult and Pediatric Patients with Asthma by Using the Physiologically Based Pharmacokinetic Approach.

Theophylline is commonly used for the treatment of asthma and has a low hepatic clearance. The changes in plasma albumin concentration occurring in asthma may affect the exposure of theophylline. The aim of the presented work was to predict theophylline pharmacokinetics (PK) after incorporating the changes in plasma albumin concentration occurring in patients with asthma into a physiologically based pharmacokinetic (PBPK) model to see whether these changes can affect the systemic theophylline concentrations in asthma. The PBPK model was developed following a systematic model building approach using Simcyp. The predictions were performed initially in healthy adults after intravenous and oral drug administration. Only when the developed adult PBPK model had adequately predicted theophylline PK in healthy adults, the changes in plasma albumin concentrations were incorporated into the model for predicting drug exposure in patients with asthma. After evaluation of the developed model in the adult population, it was scaled to children on physiologic basis. The model evaluation was performed by using visual predictive checks and comparison of ratio of observed and predicted (Robs/Pre) PK parameters along with their 2-fold error range. The developed PBPK model has effectively described theophylline PK in both healthy and diseased populations, as Robs/Pre for all the PK parameters were within the 2-fold error limit. The predictions in patients with asthma showed that there were no significant changes in PK parameters after incorporating the changes in serum albumin concentration. The mechanistic nature of the developed asthma-PBPK model can facilitate its extension to other drugs. SIGNIFICANCE STATEMENT: Exposure of a low hepatic clearance drug like theophylline may be susceptible to plasma albumin concentration changes that occur in asthma. These changes in systemic albumin concentrations can be incorporated into a physiologically based pharmacokinetic model to predict theophylline pharmacokinetics in adult and pediatric asthma populations. The presented work is focused on predicting theophylline absorption, distribution, metabolism, and elimination in adult and pediatric asthma populations after incorporating reported changes in serum albumin concentrations to see their impact on the systemic theophylline concentrations.

Bone sarcoma surgery in times of COVID-19 pandemic lockdown-early experience from a tertiary centre in India.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) lockdown has presented a unique challenge for sarcoma care. The purpose of this study is to evaluate the early results and feasibility of surgeries for bone sarcomas during the COVID-19 lockdown. METHODS: Our prospectively collected orthopaedic oncological database was reviewed to include two groups of patients- those who underwent surgery in the immediate 4 weeks before lockdown (non-lockdown group) and those operated in the first 4 weeks of lockdown (lockdown group). All patients were followed-up clinically and telephonically to collect the outcome data. RESULTS: Out of the 91 patients who qualified for inclusion, fifty were classified into the non-lockdown group while 41 patients formed the lockdown group. Both the groups were comparable with respect to baseline demographic parameters. However, during the lockdown period 37 patients (90%) had undergone a major surgical intervention as against 24 patients (48%) in the non-lockdown group (P < .001). There was no significant difference in type of anaesthesia, median estimated blood loss and procedure duration. None of the patients/health care workers had evidence of severe acute respiratory syndrome-coronavirus 2 infection at 15 days follow-up. CONCLUSION: Our study results suggest that appendicular bone tumours can be safely operated with adequate precautions during the lockdown period.

Investigation of potent inhibitors of cholinesterase based on thiourea and pyrazoline derivatives: Synthesis, inhibition assay and molecular modeling studies.

Owing to the desperate need of new drugs development to treat Alzheimer's ailment the synthesis of 1-aroyl-3-(5-(4-chlorophenyl)-1,2,4-triazole-3-thioneaminylthioureas (2-6) starting from (4-amino-5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol) (1) and synthesis of 1-(3-(4-aminophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-isobutylphenyl)propan-1-one (7-9) starting from 2-(4-isobutylphenyl)propanehydrazide (a) with the cyclization with substituted chalcones (c-e) was carried out. To check the biological potential of the synthesized compounds, all were subjected to acetylcholinesterase (AChE) and butrylcholinesterase (BChE) inhibition assays. The most potent and selective inhibitor for the acetylcholinesterase was compound 7 having an inhibitory concentration of 123 ±â€¯51 nM, whereas, compound 6 was found as selective inhibitor of butyrylcholinesterase (BChE) with an IC50 value of 201 ±â€¯80 nM. However, the compounds 1 and 2 were found as dual inhibitors i.e. active against both acetylcholinesterase as well as butyrylcholinesterase.

Processing Techniques for Scanning Electron Microscopy Imaging of Giant Cells from Giant Cell Tumors of Bone.

Giant cell tumor (GCT) of bone is a common benign lesion that causes significant morbidity due to the failure of modern medical and surgical treatment. Surface ultra-structures of giant cells (GCs) may help in distinguishing aggressive tumors from indolent GC lesions. This study aimed to standardize scanning electron microscopic (SEM) imaging of GC from GCT of bone. Fresh GCT collected in Dulbecco's Modified Eagle Medium was washed to remove blood, homogenized, or treated with collagenase to isolate the GCs. Mechanically homogenized and collagenase-digested GCs were imaged on SEM after commonly used drying methodologies such as air-drying, tetramethylsilane (TMS)-drying, freeze-drying, and critical point-drying (CPD) for the optimization of sample processing. The collagenase-treated samples yielded a greater number of isolated GC and showed better surface morphology in comparison to mechanical homogenization. Air-drying was associated with marked cell shrinkage, and freeze-dried samples showed severe cell damage. TMS methodology partially preserved the cell contour and surface structures, although the cell shape was distorted. GC images with optimum surface morphology including membrane folding and microvesicular structures on the surface were observed only in collagenase-treated and critical point-dried samples. Collagenase digestion and critical point/TMS-drying should be performed for optimal SEM imaging of individual GCs.

Shaping Ability of HyFlex EDM and ProTaper Next Rotary Instruments in Curved Root Canals: A Micro-CT Study.

AIM: The aim of this study is to evaluate and compare the shaping ability of HyFlex™ EDM (HFEDM) and ProTaper Next (PTN) rotary instruments in curved root canals by using micro-computed tomography (micro-CT) imaging. MATERIALS AND METHODS: A total of 22 mandibular molar teeth having separate mesial canals with 20 to 30° curvatures were randomly divided into two groups and instrumented with HFEDM (OneFile) or PTN (X1 and X2). Pre- and post-instrumentation micro-CT scans were obtained. Mesiodistal canal transportation and centering ability were evaluated in four cross-sections (2, 4, 6, and 8 mm from apex). Changes in canal volume and surface area were measured for a 10-mm standardized area of interest. Kolmogorov-Smirnov and Shapiro-Wilk tests were used to assess the normality and homogeneity. Independent and paired t tests and one-way ANOVA were used to analyze data at the p < 0.05 level. RESULTS: Compared to PTN, HFEDM showed significantly less mesiodistal canal transportation and improved centering ability in cross-section L6 (p < 0.05). The instruments showed similar increases in volume and surface area of the canals, with minor insignificant differences. CONCLUSION: HFEDM and PTN files were safe to use in curved canals and showed similar shaping ability, while respecting the original anatomies. HFEDM OneFile performed better at the vicinity of the danger zone in terms of mesiodistal canal transportation and centering ability.

Plant growth promoting bacteria: role in soil improvement, abiotic and biotic stress management of crops.

Agricultural production-a major contributing factor towards global food supply-is highly reliant on field crops which are under severe threats ranging from poor soil quality, biotic, abiotic stresses and changing climatic conditions. To overcome these challenges, larger exertions are required to boost production of agricultural crops in a defensible mode. Since the evolution of fertilizers and pesticides, global crop productivity has experienced an unprecedented elevation, but at the cost of environmental and ecological unsustainability. To enhance the agricultural outputs in a sustainable way, the novel and eco-friendly strategies must be employed in agriculture, which would lead to reduced use of hazardous chemicals. Thus, the utilization of our knowledge about natural growth stimulators can lead to decrease reliance on fertilizers and pesticide which are widely used for increasing crop productivity. Among beneficial microbes, plant growth promoting bacteria offers excellent opportunities for their wide utilization in agriculture to manage soil quality and other factors which correspond to limited growth and yield output of major field crops. The aim of this review is to examine the potential role of plant growth stimulating bacteria in soil fertility and enabling crops to cope with biotic and abiotic challenges.

Pharmacological validation of the folkloric uses of Cyperus rotundus L. in different ailments: An in vivo and in vitro research.

In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate the sound mechanistic background in the treatment of gastrointestinal, bronchial and vascular disorders as well as in pain, emesis, pyrexia and bacterial infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr) exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with Cr. Cr caused the rightward shift of calcium concentration response curves, similar to verapamil. Cr. Cr also caused the relaxation of K+(80 mM)- and carbachol (1 µM)-induced contractions of trachea preparations, similar to that of verapamil. Moreover, Cr. Cr also relaxed the contraction induced by the K+ (80 mM) and phenylephrine (1 µM) of aorta preparations. Data show that C. rotundus possess the spasmolytic, bronchodilator and vasodilator activities possibly through calcium channels blockade; validating its folkloric use in diarrhea, dyspepsia, bronchitis, asthma and hypertension in addition to antibacterial, antiemetic, antipyretic and analgesic activities.