Diversity of uropathogens and their antibiotic resistance among diabetic patients presented to MTI-Lady Reading Hospital, Peshawar.

Objective: Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to antibiotics. Method: A cross-sectional study was conducted at the Internal Medicine Ward of Lady Reading Hospital, Peshawar, Pakistan from June 2021 to December 2021, Patients with confirmed diabetes were included in the study; however, participants receiving antimicrobial medications for a maximum of 14 days were excluded from the study. Resistance of Escherichia coli, Candida, Pseudomonas, E. faecalis, Klebsiella, P. mirabilis and Staphylococcus was asssessed using ciprofloxac, ceftazidime and meropenem. Results: The findings highlighted the the prevalence of Escherichia coli in 38.8% of patients, Candida in 19% of patients, Enterococcus faecalis in 11.8% of patients, Pseudomonas in 10%, Klebsiella in 9.5% patients, Proteus mirabilis 6.2% patients and Staphylococcus was found in 5.2% patients. According to the overall sensitivity and resistance of antibiotics in microorganisms, Meropenem showed 89.6% sensitivity and 10.4% resistance. Ciprofloxacin showed 38.9% sensitivity and 61.1% resistance and ceftazidime showed 22.7 sensitivity and 77.3% resistance. Conclusion: UTIs were very common in diabetes patients, and Escherichia coli was the most common uropathogen found. Compared to male patients, more female patients had infections. The uropathogens showed a significant degree of resistance to ceftizidime and ciprofloxacin.

A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9).

Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms are caused by disease-causing variants in several genes, including GLI1, GLI3, ZNF141, FAM92A, IQCE, KIAA0825, MIPOL1, STKLD1, PITX1, and DACH1. Whole exome sequencing (WES) followed by bi-directional Sanger sequencing was performed for the single affected individual (II-1) of the family to reveal the disease causative variant/gene. 3D protein modeling and structural molecular docking was performed to determine the effect of the identified mutation on the overall protein structure. WES revealed a novel biallelic missense variant (c.472G>C; p.Ala158Pro) in exon 6 of the FAM92A gene. The identified variant segregated perfectly with the disease phenotype using Sanger sequencing. Furthermore, Insilco analysis revealed that the variant significantly changes the protein secondary structure, and substantially impact the stability of FAM92A. We report the second FAM92A disease-causing mutation associated with recessive non-syndromic postaxial polydactyly. The data further confirms the contribution of FAM92A in limb development and patterning.

Clinico-Biochemical Spectrum of Pakistani Patients with Glutaric Aciduria Type 1 (GA1): Experience from a Specialised Biochemical Genetics Laboratory in Pakistan.

OBJECTIVE: To evaluate the clinical, radiological, and biochemical features of glutaric aciduria Type 1 (GA1) patients identified through urine organic acid testing at a biochemical genetics laboratory (BGL) in Pakistan. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from January 2013 to December 2022. METHODOLOGY: Medical charts and urine organic acid (UOA) chromatograms of the patients presenting at the BGL from January 2013 to December 2022 were reviewed. Brain imaging was obtained where available. Variables were noted as per the objective and descriptive statistics were obtained. RESULTS: GA1 was found in 64 (0.4%) patients out of a total of 16,094 UOA requests for high-risk screening cases. The age of diagnosis ranged between one month and three years. The brain MRI findings revealed characteristic abnormalities such as cerebral atrophy, expanded CSF spaces, white matter abnormalities, and a distinct bat wings appearance, in cohesion with the results of biochemical testing. CONCLUSION: Sixty-four cases of GA1 from a single centre indicate a high frequency of the disorder in Pakistan. Late diagnosis emphasises the need for increased clinical awareness and preferably newborn screening to ensure optimal outcomes. KEY WORDS: Glutaric aciduria Type 1 (GA1), Brain imaging, UOA analysis, Glutaryl-CoA dehydrogenase (GCDH), Pakistan.

Novel strategy to raise the content of aglycone isoflavones in soymilk and gel: Effect of germination on the physicochemical properties.

Germination holds the key to nutritional equilibrium in plant grains. In this study, the effect of soybean germination on the processing of soymilk (SM) and glucono-δ-lactone (GDL) induced soymilk gel (SG) was investigated. Germination promoted soybean sprout (SS) growth by activating the energy metabolism system. The energy metabolism was high during the three-day germination and was the most vigorous on the second day of germination. After germination, protein dissolution was improved in SM, and endogenous enzymes produced small molecule proteins. Small molecule proteins were more likely to aggregate to produce SM protein particles. Germination increased the water-holding capacity of SG induced by GDL but weakened the strength. Furthermore, the dynamic fluctuations in isoflavone content were closely monitored throughout the processing of soybean products, including SS, SM, and SG. Although the total amount of isoflavones in SM and SG processed from germinated soybeans decreased, a significant enrichment in the content of aglycone isoflavones was observed. The content of aglycone isoflavones in SG processed from germinated soybeans on the second day of germination was 736.17 ± 28.49 µg/g DW, which was 83.19 % higher than that of the control group. This study demonstrates that germination can enhance the nutritional value of soybean products, providing innovative opportunities for the development of health-promoting soybean-based products.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species.

Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein-protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, -7.1, -9.0 and -8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation.

Aspiration Thrombectomy Using Inari FlowTriever System for Inferior Vena Cava Tumor Thrombus: A Case Report.

Pharmacomechanical therapy and catheter-directed thrombolysis are potent treatments for venous thromboembolism. However, limited data exist regarding the management of thrombi in the inferior vena cava (IVC). IVC thrombus resulting from tumors is a particularly uncommon condition. Managing IVC tumor thrombi poses even greater challenges, as conventional therapies such as systemic anticoagulation and thrombolysis are often ineffective. In this report, we present the case of a 73-year-old male with an inferior vena cava tumor thrombus successfully managed through aspiration thrombectomy utilizing the Inari FlowTriever system.

A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes.

INTRODUCTION: Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability. OBJECTIVE: This evaluation aims to describe the pharmacokinetics of noscapine using a semi-mechanistic population pharmacokinetic model and to identify covariates that could explain inter-individual pharmacokinetic variability. METHODS: Forty-eight healthy volunteers (30 men and 18 women, mean age 33 years) were enrolled in a randomized, two-period, two-stage, crossover bioequivalence study of noscapine in two different liquid formulations. Noscapine plasma concentrations following oral administration of noscapine 50 mg were evaluated by a non-compartmental analysis and by a population pharmacokinetic model separately. RESULTS: Compared to the reference formulation, the test formulation exhibited ratios (with 94.12% confidence intervals) of 0.784 (0.662-0.929) and 0.827 (0.762-0.925) for peak plasma concentrations and area under the plasma concentration-time curve, respectively. Significant differences in p values (< 0.01) were both observed when comparing peak plasma concentrations and area under the plasma concentration-time curve between CYP2C9 genotype-predicted phenotypes. A three-compartmental model with zero-order absorption and first-order elimination process best described the plasma data. The introduction of a liver compartment was able to describe the profound first-pass effect of noscapine. Total body weight and the CYP2C9 genotype-predicted phenotype were both identified as significant covariates on apparent clearance, which was estimated as 958 ± 548 L/h for extensive metabolizers (CYP2C9*1/*1 and *1/*9), 531 ± 304 L/h for intermediate metabolizers with an activity score of 1.5 (CYP2C9*1/*2), and 343 ± 197 L/h for poor metabolizers and intermediate metabolizers with an activity score of 1.0 (CYP2C9*1/*3, *2/*3, and*3/*3). CONCLUSION: The current work is expected to facilitate the future pharmacokinetic/pharmacodynamic development of noscapine. This study was registered prior to starting at "Deutsches Register Klinischer Studien" under registration no. DRKS00017760.

Performance enhancement of short-term wind speed forecasting model using Realtime data.

The ever-increasing demand for electricity has presented a grave threat to traditional energy sources, which are finite, rapidly depleting, and have a detrimental environmental impact. These shortcomings of conventional energy resources have caused the globe to switch from traditional to renewable energy sources. Wind power significantly contributes to carbon-free energy because it is widely accessible, inexpensive, and produces no harmful emissions. Better and more efficient renewable wind power production relies on accurate wind speed predictions. Accurate short-term wind speed forecasting is essential for effectively handling unsteady wind power generation and ensuring that wind turbines operate safely. The significant stochastic nature of the wind speed and its dynamic unpredictability makes it difficult to forecast. This paper develops a hybrid model, L-LG-S, for precise short-term wind speed forecasting to address problems in wind speed forecasting. In this research, state-of-the-art machine learning and deep learning algorithms employed in wind speed forecasting are compared with the proposed approach. The effectiveness of the proposed hybrid model is tested using real-world wind speed data from a wind turbine located in the city of Karachi, Pakistan. Moreover, the mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) are used as accuracy evaluation indices. Experimental results show that the proposed model outperforms the state-of-the-art legacy models in terms of accuracy for short-term wind speed in training, validation and test predictions by 98% respectively.

Comparative Outcomes of Peritoneal and Hemodialysis in ESRD Patients with STEMI: A National Inpatient Sample Analysis (2016-2020).

End-stage renal disease (ESRD) patients are at increased risk of mortality, particularly due to cardiovascular events such as acute myocardial infarction. Hemodialysis and peritoneal dialysis are the two main treatment modalities for ESRD patients. Using data from the National Inpatient Sample (NIS) database, we conducted a retrospective study involving 25,435 ESRD patients diagnosed with ST-elevation myocardial infarction (STEMI) between 2016 and 2020, categorized by their dialysis regimen. Our analysis revealed comparable mortality rates between peritoneal dialysis (PD) and hemodialysis (HD) patients, but lower hospitalization costs and fewer complications among PD recipients. Over five years, we observed a notable decrease in STEMI mortality despite increased STEMI cases among HD patients. Conversely, HD patients experienced increased hospital stays and associated costs over the study period than PD patients, who demonstrated stable trends. This study highlights the implications of dialysis modality selection in managing costs and reducing morbidity among STEMI patients with ESRD.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview.

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.

Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.

PURPOSE: Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM). METHODS: Twenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600 mg of rifampicin separated by a wash-out period of at least 9 days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin. RESULTS: A one-compartment model with nonlinear (Michaelis-Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height. CONCLUSION: Our results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin.

Diphtheria's Dual Threat: Amplifying Awareness of Cardiac Complications for Enhanced Intervention.

Even though immunization can prevent illness, diphtheria, which is caused by toxic strains of Corynebacterium diphtheriae, remains a serious public health risk. Although the worldwide incidence has declined, it still poses a serious hazard in developing countries, such as Pakistan, where new data suggest an increase in cases. A significant proportion of patients with respiratory diphtheria experience cardiac complications, specifically myocarditis, which carries a high death risk of 50% to 75%. The diphtheria toxin's affinity for cardiac tissues is the cause of these consequences, which include arrhythmias and myocardial dysfunction. Recent studies from Lady Reading Hospital in Peshawar show the seriousness of the situation, with 73 patients presenting with cardiac complications in just one year, resulting in a devastating fatality rate despite early management. This highlights the pressing need for increased awareness and all-encompassing immunization campaigns, particularly for children who have received insufficient vaccinations. Timely vaccination and booster doses are critical for reducing myocarditis-related mortality, mandating prioritizing immunization efforts to defend susceptible populations globally.

Diphtheria-Associated Myocarditis: Clinical Profiles and Mortality Trends in a Tertiary Care Hospital in Pakistan.

BACKGROUND: Corynebacterium diphtheriae infection, causing diphtheria, is a public health concern, particularly in developing nations like Pakistan. Despite immunization efforts, recent outbreaks since 2022 have emphasized the continuing threat. This study focuses on describing the clinical characteristics of children with diphtheria-induced myocarditis and exploring the association between early cardiac abnormalities, future fatality rates, and contributing factors. METHODS: A one-year cross-sectional study was undertaken at Lady Reading Hospital MTI Peshawar, encompassing 73 pediatric patients diagnosed with diphtheria-associated myocarditis. Data, including demographic characteristics, cardiac enzymes, and serial ECG and echocardiography data, were gathered from the health management information system (HMIS). Institutional Ethical Committee approval was obtained, and informed consent was waived due to its retrospective nature. RESULTS: Gender distribution within the study was balanced, with 35 males (47.9%) and 38 females (52.1%). ECG data revealed various prevalence rates: 27.4% for rhythm abnormalities, 20% for conduction abnormalities, 6.8% for ischemia alterations, and 20.5% for normal findings. Treatment measures included anti-diphtheria serum (ADS) in 87.7% and temporary pacemaker placement (TPM) in 13.7% of patients. Echo findings indicated a variety of cardiac dysfunctions: 53.4% with no dysfunction, 9.6% mild malfunction, 6.8% with moderate dysfunction, and 30.1% with severe dysfunction. The categorization of creatine kinase (CK), lactate dehydrogenase (LDH), and troponin I (Trop I) gave insights into the biochemical aspects. CONCLUSION: This study gives a full insight into the clinical symptoms of diphtheria-induced myocarditis in children. The findings can help establish a foundation for ongoing study into potential gender-related trends in clinical outcomes, contributing to improved care and preventative methods.

Multi-Objective Task-Aware Offloading and Scheduling Framework for Internet of Things Logistics.

IoT-based smart transportation monitors vehicles, cargo, and driver statuses for safe movement. Due to the limited computational capabilities of the sensors, the IoT devices require powerful remote servers to execute their tasks, and this phenomenon is called task offloading. Researchers have developed efficient task offloading and scheduling mechanisms for IoT devices to reduce energy consumption and response time. However, most research has not considered fault-tolerance-based job allocation for IoT logistics trucks, task and data-aware scheduling, priority-based task offloading, or multiple-parameter-based fog node selection. To overcome the limitations, we proposed a Multi-Objective Task-Aware Offloading and Scheduling Framework for IoT Logistics (MT-OSF). The proposed model prioritizes the tasks into delay-sensitive and computation-intensive tasks using a priority-based offloader and forwards the two lists to the Task-Aware Scheduler (TAS) for further processing on fog and cloud nodes. The Task-Aware Scheduler (TAS) uses a multi-criterion decision-making process, i.e., the analytical hierarchy process (AHP), to calculate the fog nodes' priority for task allocation and scheduling. The AHP decides the fog nodes' priority based on node energy, bandwidth, RAM, and MIPS power. Similarly, the TAS also calculates the shortest distance between the IoT-enabled vehicle and the fog node to which the IoT tasks are assigned for execution. A task-aware scheduler schedules delay-sensitive tasks on nearby fog nodes while allocating computation-intensive tasks to cloud data centers using the FCFS algorithm. Fault-tolerant manager is used to check task failure; if any task fails, the proposed system re-executes the tasks, and if any fog node fails, the proposed system allocates the tasks to another fog node to reduce the task failure ratio. The proposed model is simulated in iFogSim2 and demonstrates a 7% reduction in response time, 16% reduction in energy consumption, and 22% reduction in task failure ratio in comparison to Ant Colony Optimization and Round Robin.

Cardiotoxicity Induced by Capecitabine and Oxaliplatin in Gastric Cancer Treatment: A Rare Case of Cardiac Arrest and Cardiogenic Shock.

Introduction: Combination-based adjuvant chemotherapy utilising capecitabine and oxaliplatin is widely used in gastric cancer treatment. Rare but severe cardiac events such as prolonged QT, cardiac arrest and cardiogenic shock can result from their use. Case description: A 45-year-old female with gastric adenocarcinoma was started on capecitabine-oxaliplatin chemotherapy one week before presenting to the emergency department with weakness. Blood pressure was 78/56 mmHg, heart rate 140 bpm and oxygen saturation 85%. She became unresponsive with pulseless ventricular fibrillation; CPR was initiated with immediate intubation. She received two shocks with a return of spontaneous circulation. Laboratory tests revealed serum potassium (3.1 mmol/l), magnesium (1.1 mg/dl) and troponin (0.46 ng/ml). An EKG revealed sinus tachycardia with a prolonged QT interval (556 ms). The combined effects of capecitabine, oxaliplatin and electrolyte abnormalities likely contributed to the QT prolongation. An echocardiogram demonstrated an ejection fraction of 10%-15%. An emergent right-heart catheterisation showed right atrial pressure of 10 mmHg and pulmonary artery pressure of 30/18 mmHg; cardiac output and index were not recorded. An intra-aortic balloon pump was placed, and she was admitted to the ICU for cardiogenic shock requiring norepinephrine, vasopressin and dobutamine. A repeat echocardiogram showed a significantly improved ejection fraction of 65%, and she was discharged. Discussion: Capecitabine and oxaliplatin cardiotoxicity is an exceedingly rare occurrence, with both drugs reported to cause QT prolongation. Conclusion: Healthcare providers must recognise the QT prolongation effects of capecitabine and oxaliplatin, leading to life-threatening cardiac arrhythmias. LEARNING POINTS: Recognise the QT-prolonging effects of capecitabine and oxaliplatin-based chemotherapy.Recognise that cardiogenic shock and cardiac arrest with capecitabine and oxaliplatin-based chemotherapy can occur in individuals with benign cardiac history, especially early in treatment.

Scaling Supercapacitive Swing Adsorption of CO2 Using Bipolar Electrode Stacks.

Supercapacitive swing adsorption (SSA) modules with bipolar stacks having 2, 4, 8, and 12 electrode pairs made from BPL 4 × 6 activated carbon are constructed and tested for carbon dioxide capture applications. Tests are performed with simulated flue gas (15%CO2 /85%N2) at 2, 4, 8, and 12 V, respectively. Reversible adsorption with sorption capacities (≈58 mmol kg-1) and adsorption rates (≈38 µmol kg-1 s-1) are measured for all stacks. The productivity scales with the number of cells in the module, and increases from 70 to 390 mmol h-1 m-2. The energy efficiency and energy consumption improve with increasing number of bipolar electrodes from 67% to 84%, and 142 to 60 kJ mol-1, respectively. Overall, the results show that SSA modules with bipolar electrodes can be scaled without reducing the adsorptive performance, and with improvement of energetic performance.

Knowledge, attitude, and awareness of cardiopulmonary resuscitation among university enrolled medical and non-medical students of Pakistan: An online study.

Objective: To evaluate the awareness, attitude and knowledge of cardiopulmonary resuscitation (CPR) among university-enrolled medical and non-medical undergraduate students of Pakistan. Methods: Cross-sectional online survey-based study was conducted across institutes in Pakistan from December, 2022 to January, 2023. The study involved university-enrolled undergraduate students across the country. The structured questionnaire was disseminated via Google forms. For statistical analysis, SPSS version 20 was used to analyze the data by applying independent sample t-tests and ANOVA. Results: A total of 249 responses were received. After the exclusion of two responses, the overall awareness score of participants was found to be 2.49 ± 1.33, attitude score of 4.09 ± 1.74, and knowledge score of 3.51 ± 2.13. Female respondents, medical students, unmarried (single), private institutes, and respondents with educated parents achieved relatively higher scores. The overall difference in awareness scores among different regions of Pakistan was also significant (p <0.05). Gender, region, and parental literacy rate also showed effects on participants' basic life support (BLS) and CPR knowledge (p <0.05). Conclusions: Overall knowledge and awareness were unsatisfactory and inadequate in university-enrolled undergraduate students, with no one getting a complete score on very basic knowledge questions. Significant differences in awareness, attitude, and knowledge among different regions, genders, and parental literacy rates were found.

Understanding adefovir pharmacokinetics as a component of a transporter phenotyping cocktail.

PURPOSE: Adefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail. METHODS: Data from 24 healthy subjects were reanalyzed. After establishing a base model, covariate effects, including the impact of co-administered drugs, were assessed using forward inclusion then backward elimination. RESULTS: A one-compartment model with first-order absorption (including lag time) and a combination of nonlinear renal and linear nonrenal elimination best described the data. A significantly higher apparent bioavailability (73.6% vs. 59.0%) and a lower apparent absorption rate constant (2.29 h-1 vs. 5.18 h-1) were identified in the combined period compared to the sole administration period, while no difference was seen in renal elimination. The population estimate for the Michaelis-Menten constant (Km) of the nonlinear renal elimination was 170 nmol/L, exceeding the observed range of adefovir plasma maximum concentration, while the maximum rate (Vmax) of nonlinear renal elimination was 2.40 µmol/h at the median absolute estimated glomerular filtration rate of 105 mL/min. CONCLUSION: The popPK modeling approach indicated that the co-administration primarily affected the apparent absorption and/or prodrug conversion of adefovir dipivoxil, resulting in the minor drug-drug interaction observed for adefovir as a victim. However, renal elimination remained unaffected. The high Km value suggests that assessing renal OAT1 activity by CLR has no relevant misspecification error with the cocktail doses used.

Silver oxide doped iron oxide/alginate nanocomposite coated cotton cloth for selective catalytic reduction of potassium ferricyanide.

Silver oxide doped iron oxide (Ag2O-Fe2O3) nanocatalyst was prepared and coated on cotton cloth (CC) as well as wrapped in sodium alginate (Alg) hydrogel. Ag2O-Fe2O3 coated CC (Ag2O-Fe2O3/CC) and Ag2O-Fe2O3 wrapped Alg (Ag2O-Fe2O3/Alg) were utilized as catalysts in reduction reaction of 4-nitrophenol (4-NP), congo red (CR), methylene blue (MB) and potassium ferricyanide (K3[Fe(CN)6]). Ag2O-Fe2O3/CC and Ag2O-Fe2O3/Alg were found to be effective and selective catalyst for the reaction of K3[Fe(CN)6]. Further amount of catalyst, K3[Fe(CN)6] quantity, amount of NaBH4, stability of catalyst and recyclability were optimized for the reaction of K3[Fe(CN)6] reduction. Ag2O-Fe2O3/Alg and Ag2O-Fe2O3/CC were appeared to be the stable catalysts by maintaining high activity during recyclability tests showing highest reaction rate constants (kapp) of 0.3472 and 0.5629 min-1, correspondingly. However, Ag2O-Fe2O3/CC can be easily recovered as compared to Ag2O-Fe2O3/Alg by simply removing from the reaction which is the main advantage of Ag2O-Fe2O3/CC. Moreover, Ag2O-Fe2O3/Alg and Ag2O-Fe2O3/CC were also examined in real samples and found useful for K3[Fe(CN)6] reduction involving real samples. The Ag2O-Fe2O3/CC nanocatalyst is a cost and time saving material for economical reduction of K3[Fe(CN)6] and environmental safety.